Advances in Respiratory Medicine Latest open access articles published in Adv. Respir. Med. at https://www.mdpi.com/journal/arm https://www.mdpi.com/journal/arm MDPI en Creative Commons Attribution (CC-BY) MDPI support@mdpi.com ARM, Vol. 94, Pages 34: Epidemiological Analysis of Hospitalized Children with Acute Asthma Exacerbation over 30 Years https://www.mdpi.com/2543-6031/94/3/34 Objectives: To provide an evidence-based reference for preventing and managing pediatric acute asthma exacerbations by examining epidemiology and long-term trends of hospitalized cases in a tertiary hospital in Beijing over 30 years. Methods: Retrospective analysis of clinical data from children hospitalized for acute asthma exacerbation at Peking University Third Hospital from 1994 to 2023. Data collected included demographics, onset timing, and hospital stay duration, with distribution patterns analyzed across ages, years, seasons, and months. Results: The study included 1106 patients (65.73% male, 34.27% female) with a median age of 4 years. Hospitalizations peaked in 1999 (8.40%) and declined, reaching the lowest point in 2020 (1.45%) coinciding with the COVID-19 pandemic. Most admissions occurred in autumn (34.27%), especially in October (13.29%). The average hospital stay was 5.35 ± 2.65 days, longest for toddlers. Conclusions: Over 30 years, pediatric hospitalizations for acute asthma exacerbations in this tertiary center have shown a declining trend, suggesting improved asthma management. However, the persistent autumn peak and male predominance highlight the need for targeted prevention strategies—particularly for male and preschool-aged children before the autumn school term—to further reduce acute exacerbations and hospitalizations. 2026-05-29 ARM, Vol. 94, Pages 34: Epidemiological Analysis of Hospitalized Children with Acute Asthma Exacerbation over 30 Years

Advances in Respiratory Medicine doi: 10.3390/arm94030034

Authors: Xuee Zhuang Mengyuan Liu Kunhong Lin Yangxin Xiao Xuyan Zhao Zifan Gai Yan Xing

Objectives: To provide an evidence-based reference for preventing and managing pediatric acute asthma exacerbations by examining epidemiology and long-term trends of hospitalized cases in a tertiary hospital in Beijing over 30 years. Methods: Retrospective analysis of clinical data from children hospitalized for acute asthma exacerbation at Peking University Third Hospital from 1994 to 2023. Data collected included demographics, onset timing, and hospital stay duration, with distribution patterns analyzed across ages, years, seasons, and months. Results: The study included 1106 patients (65.73% male, 34.27% female) with a median age of 4 years. Hospitalizations peaked in 1999 (8.40%) and declined, reaching the lowest point in 2020 (1.45%) coinciding with the COVID-19 pandemic. Most admissions occurred in autumn (34.27%), especially in October (13.29%). The average hospital stay was 5.35 ± 2.65 days, longest for toddlers. Conclusions: Over 30 years, pediatric hospitalizations for acute asthma exacerbations in this tertiary center have shown a declining trend, suggesting improved asthma management. However, the persistent autumn peak and male predominance highlight the need for targeted prevention strategies—particularly for male and preschool-aged children before the autumn school term—to further reduce acute exacerbations and hospitalizations.

]]> Epidemiological Analysis of Hospitalized Children with Acute Asthma Exacerbation over 30 Years Xuee Zhuang Mengyuan Liu Kunhong Lin Yangxin Xiao Xuyan Zhao Zifan Gai Yan Xing doi: 10.3390/arm94030034 Advances in Respiratory Medicine 2026-05-29 Advances in Respiratory Medicine 2026-05-29 94 3 Article 34 10.3390/arm94030034 https://www.mdpi.com/2543-6031/94/3/34 ARM, Vol. 94, Pages 33: Pulmonary Actinomycosis: A Hidden Threat with Clinical Impact https://www.mdpi.com/2543-6031/94/3/33 Background: Pulmonary actinomycosis is a rare chronic infection that frequently mimics lung malignancy, often leading to delayed diagnosis due to its non-specific clinical and radiological presentation. Given the diagnostic challenges associated with this condition, the aim of this study was to evaluate the clinical presentation, diagnostic pathways, treatment strategies, and outcomes of patients diagnosed with pulmonary actinomycosis in a single center. Methods: We retrospectively reviewed patients diagnosed with pulmonary actinomycosis at our institution between January 2014 and December 2022. Diagnosis was established based on compatible clinical and radiological findings together with microbiological identification of Actinomyces by culture or polymerase chain reaction. Results: Twenty-two patients were included in the final analysis. The median age was 61.5 years and males were more frequently affected (59%). The median time from initial hospitalization to definitive diagnosis was 70 days. Actinomyces odontolyticus was the most frequently identified species. All patients received antibiotic therapy, with a median treatment duration of 45.5 days. Thirteen patients underwent surgical intervention, performed either for diagnostic purposes or for treatment of complications. Complete disease eradication through surgical management was achieved in six cases. During follow-up (median 24 months), overall survival at three years was 78%, with one death directly related to pulmonary actinomycosis. Conclusions: Pulmonary actinomycosis remains a diagnostic challenge due to its non-specific clinical presentation and low microbiological yield. Early clinical suspicion and a combined diagnostic approach including bronchoscopy and microbiological testing are essential for timely diagnosis. Surgical intervention may play an important diagnostic and therapeutic role in selected patients. 2026-05-18 ARM, Vol. 94, Pages 33: Pulmonary Actinomycosis: A Hidden Threat with Clinical Impact

Advances in Respiratory Medicine doi: 10.3390/arm94030033

Authors: Raffaella Griffo Jasmin K. Jasuja Benedikt Niedermaier Sabine Wege Janina Shala Henrike Deissner Lena Brendel Romina M. Rösch Florian Eichhorn Michael Allgäuer Elizabeth Tong Cosmas Wimmer Martin E. Eichhorn Hauke Winter Laura V. Klotz

Background: Pulmonary actinomycosis is a rare chronic infection that frequently mimics lung malignancy, often leading to delayed diagnosis due to its non-specific clinical and radiological presentation. Given the diagnostic challenges associated with this condition, the aim of this study was to evaluate the clinical presentation, diagnostic pathways, treatment strategies, and outcomes of patients diagnosed with pulmonary actinomycosis in a single center. Methods: We retrospectively reviewed patients diagnosed with pulmonary actinomycosis at our institution between January 2014 and December 2022. Diagnosis was established based on compatible clinical and radiological findings together with microbiological identification of Actinomyces by culture or polymerase chain reaction. Results: Twenty-two patients were included in the final analysis. The median age was 61.5 years and males were more frequently affected (59%). The median time from initial hospitalization to definitive diagnosis was 70 days. Actinomyces odontolyticus was the most frequently identified species. All patients received antibiotic therapy, with a median treatment duration of 45.5 days. Thirteen patients underwent surgical intervention, performed either for diagnostic purposes or for treatment of complications. Complete disease eradication through surgical management was achieved in six cases. During follow-up (median 24 months), overall survival at three years was 78%, with one death directly related to pulmonary actinomycosis. Conclusions: Pulmonary actinomycosis remains a diagnostic challenge due to its non-specific clinical presentation and low microbiological yield. Early clinical suspicion and a combined diagnostic approach including bronchoscopy and microbiological testing are essential for timely diagnosis. Surgical intervention may play an important diagnostic and therapeutic role in selected patients.

]]> Pulmonary Actinomycosis: A Hidden Threat with Clinical Impact Raffaella Griffo Jasmin K. Jasuja Benedikt Niedermaier Sabine Wege Janina Shala Henrike Deissner Lena Brendel Romina M. Rösch Florian Eichhorn Michael Allgäuer Elizabeth Tong Cosmas Wimmer Martin E. Eichhorn Hauke Winter Laura V. Klotz doi: 10.3390/arm94030033 Advances in Respiratory Medicine 2026-05-18 Advances in Respiratory Medicine 2026-05-18 94 3 Article 33 10.3390/arm94030033 https://www.mdpi.com/2543-6031/94/3/33 ARM, Vol. 94, Pages 32: Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches https://www.mdpi.com/2543-6031/94/3/32 This scoping review synthesized evidence on the psychosocial burden of tuberculosis (TB) and on evidence-based psychosocial interventions aimed at improving treatment adherence. Specifically, it examined: (a) the most frequent mental health problems associated with TB; (b) the main barriers to adherence; (c) the components and effects of psychosocial interventions; and (d) gaps in the literature and directions for future research. Bibliographic searches were conducted in PubMed and Scopus, covering articles published between 2005 and 2025. Nineteen studies met the inclusion criteria. Depression and anxiety were the most frequently reported mental health problems, while psychosis appeared mainly in multidrug-resistant TB (MDR-TB) populations. Across studies, stigma, fear of transmission, socioeconomic disadvantage, treatment duration, and medication side effects emerged as major barriers to adherence. Evidence-based interventions—including psychoeducation, motivational enhancement therapy, cognitive behavioral therapy, acceptance and commitment therapy, and multicomponent psychosocial support—were associated with improved psychological outcomes and, in several studies, better adherence-related indicators. Overall, the evidence suggests that psychosocial distress is common among people with TB and may compromise treatment engagement. Integrating psychosocial and mental health support into TB services may therefore strengthen adherence and improve patient-centered outcomes, although more rigorous and context-sensitive research is still needed. 2026-05-15 ARM, Vol. 94, Pages 32: Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches

Advances in Respiratory Medicine doi: 10.3390/arm94030032

Authors: Rana Abdullah Bin Qamar Henrique Pereira Felipe Alckmin-Carvalho

This scoping review synthesized evidence on the psychosocial burden of tuberculosis (TB) and on evidence-based psychosocial interventions aimed at improving treatment adherence. Specifically, it examined: (a) the most frequent mental health problems associated with TB; (b) the main barriers to adherence; (c) the components and effects of psychosocial interventions; and (d) gaps in the literature and directions for future research. Bibliographic searches were conducted in PubMed and Scopus, covering articles published between 2005 and 2025. Nineteen studies met the inclusion criteria. Depression and anxiety were the most frequently reported mental health problems, while psychosis appeared mainly in multidrug-resistant TB (MDR-TB) populations. Across studies, stigma, fear of transmission, socioeconomic disadvantage, treatment duration, and medication side effects emerged as major barriers to adherence. Evidence-based interventions—including psychoeducation, motivational enhancement therapy, cognitive behavioral therapy, acceptance and commitment therapy, and multicomponent psychosocial support—were associated with improved psychological outcomes and, in several studies, better adherence-related indicators. Overall, the evidence suggests that psychosocial distress is common among people with TB and may compromise treatment engagement. Integrating psychosocial and mental health support into TB services may therefore strengthen adherence and improve patient-centered outcomes, although more rigorous and context-sensitive research is still needed.

]]> Psychosocial Interventions for Improving Treatment Adherence in Tuberculosis Patients: A Scoping Review of Evidence-Based Approaches Rana Abdullah Bin Qamar Henrique Pereira Felipe Alckmin-Carvalho doi: 10.3390/arm94030032 Advances in Respiratory Medicine 2026-05-15 Advances in Respiratory Medicine 2026-05-15 94 3 Review 32 10.3390/arm94030032 https://www.mdpi.com/2543-6031/94/3/32 ARM, Vol. 94, Pages 31: Association Between Air Pollution and Childhood Asthma: A Systematic Review of Recent Evidence https://www.mdpi.com/2543-6031/94/3/31 Background: Air pollution is a major environmental determinant of respiratory health and a significant contributor to the global burden of childhood asthma. Although several recent narrative and systematic reviews have examined environmental triggers of asthma, highlighting air pollution as a consistent risk factor across diverse populations and study designs, recent epidemiological evidence—including multicenter cohort studies and region-specific analyses from Europe and Greece—has not been systematically synthesized. Objective: To systematically review recent epidemiological evidence (2000–2025) on the association between ambient air pollution and childhood asthma incidence and exacerbations, with emphasis on European and Greek populations. Methods: Following PRISMA guidelines, we systematically reviewed observational studies published between 2000 and 2025 in PubMed, Scopus, Web of Science, BMC, and Google Scholar. Studies evaluating quantitative exposure to PM2.5, PM10, NO2, O3, or SO2 and asthma incidence, prevalence, or exacerbations in children (≤18 years) were included. Evidence was synthesized by pollutant type, exposure window, geographic region, and study design. Results: Twenty-four studies involving more than 3.5 million children were included. Consistent associations were observed across international and European cohorts between long-term exposure to PM2.5, PM10, and NO2 and increased asthma incidence. Risk estimates typically ranged from 15% to 30% increases in asthma incidence per 10 μg/m3 increase in long-term exposure to PM2.5 or NO2, as reported across multiple cohort analyses. Early-life exposure showed the strongest effects on asthma development and lung function decline. European and Greek studies demonstrated comparable trends, highlighting increased hospitalizations and symptom burden in urban populations despite pollutant concentrations often below current regulatory thresholds. Short-term pollution peaks were additionally associated with increased asthma exacerbations and hospital admissions, particularly during seasonal episodes of elevated particulate matter and ozone concentrations. Conclusions: This review provides an updated synthesis of 21st-century evidence demonstrating that ambient air pollution is a major and modifiable determinant of childhood asthma. The consistency of findings across regions, combined with limited longitudinal evidence from Greece, highlight the importance of improved air-quality management and continued public-health efforts to reduce exposure and the need for enhanced epidemiological monitoring. 2026-05-12 ARM, Vol. 94, Pages 31: Association Between Air Pollution and Childhood Asthma: A Systematic Review of Recent Evidence

Advances in Respiratory Medicine doi: 10.3390/arm94030031

Authors: Maria Kyrmanidou Ioannis Smaraidos Asterios Kampouras

Background: Air pollution is a major environmental determinant of respiratory health and a significant contributor to the global burden of childhood asthma. Although several recent narrative and systematic reviews have examined environmental triggers of asthma, highlighting air pollution as a consistent risk factor across diverse populations and study designs, recent epidemiological evidence—including multicenter cohort studies and region-specific analyses from Europe and Greece—has not been systematically synthesized. Objective: To systematically review recent epidemiological evidence (2000–2025) on the association between ambient air pollution and childhood asthma incidence and exacerbations, with emphasis on European and Greek populations. Methods: Following PRISMA guidelines, we systematically reviewed observational studies published between 2000 and 2025 in PubMed, Scopus, Web of Science, BMC, and Google Scholar. Studies evaluating quantitative exposure to PM2.5, PM10, NO2, O3, or SO2 and asthma incidence, prevalence, or exacerbations in children (≤18 years) were included. Evidence was synthesized by pollutant type, exposure window, geographic region, and study design. Results: Twenty-four studies involving more than 3.5 million children were included. Consistent associations were observed across international and European cohorts between long-term exposure to PM2.5, PM10, and NO2 and increased asthma incidence. Risk estimates typically ranged from 15% to 30% increases in asthma incidence per 10 μg/m3 increase in long-term exposure to PM2.5 or NO2, as reported across multiple cohort analyses. Early-life exposure showed the strongest effects on asthma development and lung function decline. European and Greek studies demonstrated comparable trends, highlighting increased hospitalizations and symptom burden in urban populations despite pollutant concentrations often below current regulatory thresholds. Short-term pollution peaks were additionally associated with increased asthma exacerbations and hospital admissions, particularly during seasonal episodes of elevated particulate matter and ozone concentrations. Conclusions: This review provides an updated synthesis of 21st-century evidence demonstrating that ambient air pollution is a major and modifiable determinant of childhood asthma. The consistency of findings across regions, combined with limited longitudinal evidence from Greece, highlight the importance of improved air-quality management and continued public-health efforts to reduce exposure and the need for enhanced epidemiological monitoring.

]]> Association Between Air Pollution and Childhood Asthma: A Systematic Review of Recent Evidence Maria Kyrmanidou Ioannis Smaraidos Asterios Kampouras doi: 10.3390/arm94030031 Advances in Respiratory Medicine 2026-05-12 Advances in Respiratory Medicine 2026-05-12 94 3 Review 31 10.3390/arm94030031 https://www.mdpi.com/2543-6031/94/3/31 ARM, Vol. 94, Pages 30: Antifibrotic Drugs Regulate the Expression of Epithelial Sodium Channels in the Lungs https://www.mdpi.com/2543-6031/94/3/30 Purpose: A high-salt extracellular environment promotes fibrosis in multiple organs by inducing oxidative stress, fibroblast activation, and extracellular matrix remodeling. In the lung, sodium accumulation may result from impaired epithelial ion transport. Transforming growth factor-β1 (TGF-β1), a key profibrotic cytokine, downregulates epithelial sodium and chloride channels, promoting sodium retention and fibrotic remodeling. This study investigated whether antifibrotic drugs can prevent TGF-β1-induced suppression of sodium channel expression in the lung epithelium. Methods: Human A549 alveolar epithelial cells and primary alveolar epithelial cells were cultured with or without TGF-β1 in the presence or absence of nintedanib or pirfenidone. Expression of epithelial sodium channel (ENaC) subunits (SCNN1A, SCNN1B, SCNN1G, SCNN1D) and CFTR was analyzed. In vivo, lung tissues from TGF-β1 transgenic mice and wild-type controls were examined following intranasal administration of pirfenidone. Results: TGF-β1 markedly reduced the expression of all ENaC subunits and CFTR in vitro. Nintedanib prevented suppression of SCNN1A, SCNN1D, and SCNN1G, whereas pirfenidone prevented suppression of SCNN1A, SCNN1B, and SCNN1G. In TGF-β1 transgenic mice, Scnn1a, Scnn1b, and Scnn1g expression was significantly decreased compared with wild-type controls. Pirfenidone administration dose-dependently restored expression of these ENaC subunits in vivo. Conclusions: Antifibrotic drugs partially prevent TGF-β1-induced suppression of epithelial sodium channels, preserving epithelial ion homeostasis. Restoration of ENaC expression may represent a novel mechanism by which antifibrotic therapy mitigates sodium-associated lung fibrosis. 2026-04-29 ARM, Vol. 94, Pages 30: Antifibrotic Drugs Regulate the Expression of Epithelial Sodium Channels in the Lungs

Advances in Respiratory Medicine doi: 10.3390/arm94030030

Authors: Toshiyuki Ito Hajime Fujimoto Masaaki Toda Valeria Fridman D’Alessandro Corina N. D’Alessandro-Gabazza Yurie Kogue Tatsuki Tsuruga Tomohito Okano Kazuki Furuhashi Haruko Saiki Atsushi Tomaru Esteban C. Gabazza Taro Yasuma Tetsu Kobayashi

Purpose: A high-salt extracellular environment promotes fibrosis in multiple organs by inducing oxidative stress, fibroblast activation, and extracellular matrix remodeling. In the lung, sodium accumulation may result from impaired epithelial ion transport. Transforming growth factor-β1 (TGF-β1), a key profibrotic cytokine, downregulates epithelial sodium and chloride channels, promoting sodium retention and fibrotic remodeling. This study investigated whether antifibrotic drugs can prevent TGF-β1-induced suppression of sodium channel expression in the lung epithelium. Methods: Human A549 alveolar epithelial cells and primary alveolar epithelial cells were cultured with or without TGF-β1 in the presence or absence of nintedanib or pirfenidone. Expression of epithelial sodium channel (ENaC) subunits (SCNN1A, SCNN1B, SCNN1G, SCNN1D) and CFTR was analyzed. In vivo, lung tissues from TGF-β1 transgenic mice and wild-type controls were examined following intranasal administration of pirfenidone. Results: TGF-β1 markedly reduced the expression of all ENaC subunits and CFTR in vitro. Nintedanib prevented suppression of SCNN1A, SCNN1D, and SCNN1G, whereas pirfenidone prevented suppression of SCNN1A, SCNN1B, and SCNN1G. In TGF-β1 transgenic mice, Scnn1a, Scnn1b, and Scnn1g expression was significantly decreased compared with wild-type controls. Pirfenidone administration dose-dependently restored expression of these ENaC subunits in vivo. Conclusions: Antifibrotic drugs partially prevent TGF-β1-induced suppression of epithelial sodium channels, preserving epithelial ion homeostasis. Restoration of ENaC expression may represent a novel mechanism by which antifibrotic therapy mitigates sodium-associated lung fibrosis.

]]> Antifibrotic Drugs Regulate the Expression of Epithelial Sodium Channels in the Lungs Toshiyuki Ito Hajime Fujimoto Masaaki Toda Valeria Fridman D’Alessandro Corina N. D’Alessandro-Gabazza Yurie Kogue Tatsuki Tsuruga Tomohito Okano Kazuki Furuhashi Haruko Saiki Atsushi Tomaru Esteban C. Gabazza Taro Yasuma Tetsu Kobayashi doi: 10.3390/arm94030030 Advances in Respiratory Medicine 2026-04-29 Advances in Respiratory Medicine 2026-04-29 94 3 Brief Report 30 10.3390/arm94030030 https://www.mdpi.com/2543-6031/94/3/30 ARM, Vol. 94, Pages 29: Inflammatory Biomarkers and Outcome Heterogeneity in Anti-MDA5 Antibody-Associated Interstitial Lung Disease: A Single-Center Consecutive Cohort Study https://www.mdpi.com/2543-6031/94/3/29 Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive interstitial lung disease (ILD) is associated with high mortality. While inflammatory markers have been linked to poor outcomes, clinical heterogeneity remains evident, as some patients survive despite marked hyperinflammation. Methods: We retrospectively analyzed consecutive patients with anti-MDA5 antibody-positive ILD treated at our institution between May 2017 and November 2025. In-hospital mortality was assessed in relation to clinical characteristics and laboratory markers, including peak anti-MDA5 antibody titers, ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH), and KL-6. Analyses were exploratory and hypothesis-generating. Continuous variables were compared using Mann–Whitney U tests, and categorical variables using Fisher’s exact test. Principal component analysis (PCA) and receiver operating characteristic (ROC) analyses were performed for descriptive purposes. Results: Seventeen patients were included (10 survivors and 7 non-survivors). Peak ferritin, C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels were significantly higher in non-survivors, whereas peak anti-MDA5 antibody titers showed a non-significant trend toward higher values in non-survivors (p = 0.057). KL-6 levels did not differ significantly between groups. In ROC analyses, LDH and CRP showed the highest discriminative performance for in-hospital mortality, followed by ferritin, whereas KL-6 showed the lowest discriminative performance. Despite these overall trends, substantial overlap between survivors and non-survivors remained across all biomarkers. Principal component analysis (PCA) demonstrated partial separation of outcomes along an inflammation-dominant axis, but with persistent overlap, indicating marked outcome heterogeneity. Conclusions: Inflammatory biomarkers, particularly LDH, CRP, and ferritin, were associated with in-hospital mortality in anti-MDA5 antibody-associated ILD. However, persistent overlap between survivors and non-survivors suggests that single-biomarker assessment is insufficient for precise prognostication. These findings should be interpreted as hypothesis-generating and require validation in larger multicenter cohorts. 2026-04-28 ARM, Vol. 94, Pages 29: Inflammatory Biomarkers and Outcome Heterogeneity in Anti-MDA5 Antibody-Associated Interstitial Lung Disease: A Single-Center Consecutive Cohort Study

Advances in Respiratory Medicine doi: 10.3390/arm94030029

Authors: Akina Nigi Keisuke Iwamoto Hidetoshi Itani Shigeto Kondou Yuki Okunishi Takahiro Ohnishi

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive interstitial lung disease (ILD) is associated with high mortality. While inflammatory markers have been linked to poor outcomes, clinical heterogeneity remains evident, as some patients survive despite marked hyperinflammation. Methods: We retrospectively analyzed consecutive patients with anti-MDA5 antibody-positive ILD treated at our institution between May 2017 and November 2025. In-hospital mortality was assessed in relation to clinical characteristics and laboratory markers, including peak anti-MDA5 antibody titers, ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH), and KL-6. Analyses were exploratory and hypothesis-generating. Continuous variables were compared using Mann–Whitney U tests, and categorical variables using Fisher’s exact test. Principal component analysis (PCA) and receiver operating characteristic (ROC) analyses were performed for descriptive purposes. Results: Seventeen patients were included (10 survivors and 7 non-survivors). Peak ferritin, C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels were significantly higher in non-survivors, whereas peak anti-MDA5 antibody titers showed a non-significant trend toward higher values in non-survivors (p = 0.057). KL-6 levels did not differ significantly between groups. In ROC analyses, LDH and CRP showed the highest discriminative performance for in-hospital mortality, followed by ferritin, whereas KL-6 showed the lowest discriminative performance. Despite these overall trends, substantial overlap between survivors and non-survivors remained across all biomarkers. Principal component analysis (PCA) demonstrated partial separation of outcomes along an inflammation-dominant axis, but with persistent overlap, indicating marked outcome heterogeneity. Conclusions: Inflammatory biomarkers, particularly LDH, CRP, and ferritin, were associated with in-hospital mortality in anti-MDA5 antibody-associated ILD. However, persistent overlap between survivors and non-survivors suggests that single-biomarker assessment is insufficient for precise prognostication. These findings should be interpreted as hypothesis-generating and require validation in larger multicenter cohorts.

]]> Inflammatory Biomarkers and Outcome Heterogeneity in Anti-MDA5 Antibody-Associated Interstitial Lung Disease: A Single-Center Consecutive Cohort Study Akina Nigi Keisuke Iwamoto Hidetoshi Itani Shigeto Kondou Yuki Okunishi Takahiro Ohnishi doi: 10.3390/arm94030029 Advances in Respiratory Medicine 2026-04-28 Advances in Respiratory Medicine 2026-04-28 94 3 Article 29 10.3390/arm94030029 https://www.mdpi.com/2543-6031/94/3/29 ARM, Vol. 94, Pages 28: Validation of SpO2/FiO2 as a Non-Invasive Surrogate of PaO2/FiO2 in Mechanically Ventilated COVID-19 Patients at High Altitude https://www.mdpi.com/2543-6031/94/3/28 Background: The ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) is central to the classification of acute respiratory distress syndrome (ARDS). However, its assessment requires arterial blood gas analysis, which may be limited by availability, cost, and invasiveness. Consequently, the ratio of peripheral oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) has been proposed as a non-invasive surrogate for estimating the degree of oxygenation impairment. Methods: A retrospective cross-sectional study was conducted in adult patients with COVID-19 admitted to the intensive care unit at an altitude of 2600 m above sea level (m.a.s.l.). Spearman correlation coefficients were calculated to assess the association between the SpO2/FiO2 and PaO2/FiO2 ratios and their corresponding imputation models. A generalized linear model was applied, and the diagnostic performance of the SpO2/FiO2 ratio and the imputation models for detecting severe and non-severe hypoxemia (PaO2/FiO2 cutoff value of 150) was evaluated using the area under the receiver operating characteristic curve (AUC). Results: A total of 473 patients receiving invasive mechanical ventilation were included, with a mean age of 62.4 years (SD 14.1), and a predominance of males (67.2%). An SpO2/FiO2 ratio cutoff value of ≥206 demonstrated excellent diagnostic performance, with an AUC of 0.983 (95% CI 0.97–0.99), high sensitivity (90.6%), high specificity (96.7%), and an overall correct classification rate of 93.9%. This performance remained consistent across multiple clinical scenarios. In patients with positive end-expiratory pressure > 10 cmH2O, the AUC was 0.982, with a specificity of 97.7%. In the presence of hyperbilirubinemia (total bilirubin ≥ 3 mg/dL), the AUC was 0.951. Among patients with hemoglobin levels < 10 g/dL, sensitivity reached 100%, although specificity was reduced. In the subgroup with arterial partial pressure of carbon dioxide > 35 mmHg, an SpO2/FiO2 ratio ≥ 206 showed near-perfect specificity (99.4%) and a positive likelihood ratio of 120.9. Conclusions: The SpO2/FiO2 ratio is a reliable and non-invasive surrogate of the PaO2/FiO2 ratio in mechanically ventilated patients with COVID-19 living at high altitude, particularly for the identification of non-severe hypoxemia. 2026-04-28 ARM, Vol. 94, Pages 28: Validation of SpO2/FiO2 as a Non-Invasive Surrogate of PaO2/FiO2 in Mechanically Ventilated COVID-19 Patients at High Altitude

Advances in Respiratory Medicine doi: 10.3390/arm94030028

Authors: Guillermo Ortiz-Ruiz Manuel Garay-Fernández Eduardo Tuta-Quintero Alirio Bastidas Antonio Lara Arlen Mauricio Márquez Carolina Aponte Jairo Guevara Jonathan A. Guezguan

Background: The ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) is central to the classification of acute respiratory distress syndrome (ARDS). However, its assessment requires arterial blood gas analysis, which may be limited by availability, cost, and invasiveness. Consequently, the ratio of peripheral oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) has been proposed as a non-invasive surrogate for estimating the degree of oxygenation impairment. Methods: A retrospective cross-sectional study was conducted in adult patients with COVID-19 admitted to the intensive care unit at an altitude of 2600 m above sea level (m.a.s.l.). Spearman correlation coefficients were calculated to assess the association between the SpO2/FiO2 and PaO2/FiO2 ratios and their corresponding imputation models. A generalized linear model was applied, and the diagnostic performance of the SpO2/FiO2 ratio and the imputation models for detecting severe and non-severe hypoxemia (PaO2/FiO2 cutoff value of 150) was evaluated using the area under the receiver operating characteristic curve (AUC). Results: A total of 473 patients receiving invasive mechanical ventilation were included, with a mean age of 62.4 years (SD 14.1), and a predominance of males (67.2%). An SpO2/FiO2 ratio cutoff value of ≥206 demonstrated excellent diagnostic performance, with an AUC of 0.983 (95% CI 0.97–0.99), high sensitivity (90.6%), high specificity (96.7%), and an overall correct classification rate of 93.9%. This performance remained consistent across multiple clinical scenarios. In patients with positive end-expiratory pressure > 10 cmH2O, the AUC was 0.982, with a specificity of 97.7%. In the presence of hyperbilirubinemia (total bilirubin ≥ 3 mg/dL), the AUC was 0.951. Among patients with hemoglobin levels < 10 g/dL, sensitivity reached 100%, although specificity was reduced. In the subgroup with arterial partial pressure of carbon dioxide > 35 mmHg, an SpO2/FiO2 ratio ≥ 206 showed near-perfect specificity (99.4%) and a positive likelihood ratio of 120.9. Conclusions: The SpO2/FiO2 ratio is a reliable and non-invasive surrogate of the PaO2/FiO2 ratio in mechanically ventilated patients with COVID-19 living at high altitude, particularly for the identification of non-severe hypoxemia.

]]> Validation of SpO2/FiO2 as a Non-Invasive Surrogate of PaO2/FiO2 in Mechanically Ventilated COVID-19 Patients at High Altitude Guillermo Ortiz-Ruiz Manuel Garay-Fernández Eduardo Tuta-Quintero Alirio Bastidas Antonio Lara Arlen Mauricio Márquez Carolina Aponte Jairo Guevara Jonathan A. Guezguan doi: 10.3390/arm94030028 Advances in Respiratory Medicine 2026-04-28 Advances in Respiratory Medicine 2026-04-28 94 3 Article 28 10.3390/arm94030028 https://www.mdpi.com/2543-6031/94/3/28 ARM, Vol. 94, Pages 27: Exploratory Changes in Surfactant Protein D During Intermittent Hypoxia and Modulation by Galectin-3 Inhibition https://www.mdpi.com/2543-6031/94/3/27 Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η2 = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation. 2026-04-24 ARM, Vol. 94, Pages 27: Exploratory Changes in Surfactant Protein D During Intermittent Hypoxia and Modulation by Galectin-3 Inhibition

Advances in Respiratory Medicine doi: 10.3390/arm94030027

Authors: Saad Al-Anazi Yasser A. Alshawakir Syed Shahid Habib Hayam Gad Asma F. Alotaibi Alanoud T. Aljasham Wajd Ahmed Althakfi Mohamed A. Mekhtiche Abeer Abdulmoati Al-Masri

Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η2 = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation.

]]> Exploratory Changes in Surfactant Protein D During Intermittent Hypoxia and Modulation by Galectin-3 Inhibition Saad Al-Anazi Yasser A. Alshawakir Syed Shahid Habib Hayam Gad Asma F. Alotaibi Alanoud T. Aljasham Wajd Ahmed Althakfi Mohamed A. Mekhtiche Abeer Abdulmoati Al-Masri doi: 10.3390/arm94030027 Advances in Respiratory Medicine 2026-04-24 Advances in Respiratory Medicine 2026-04-24 94 3 Article 27 10.3390/arm94030027 https://www.mdpi.com/2543-6031/94/3/27 ARM, Vol. 94, Pages 26: Biomechanical Phenotyping of Forced Expiration for Precision Pulmonary Rehabilitation: A Machine Learning Approach to Identify Structural and Kinetic Drivers https://www.mdpi.com/2543-6031/94/2/26 Background: Standard spirometry fundamentally overlooks the mechanical dynamics of forced expiration. This study derived novel biomechanical parameters to establish functional phenotypes and predict clinical respiratory impairments. Methods: Utilizing 16,596 acceptable spirometry records from NHANES (2007 to 2012), parameters reflecting kinetic power, mass constraint, and airway instability were mathematically derived. Principal component analysis, K-means clustering, and a Multilayer Perceptron neural network were sequentially applied. Results: Three distinct biomechanical phenotypes emerged: Load-Constrained (45.4%), Mechanically Efficient (23.5%), and Dynamic Collapse (31.0%). Aging significantly degraded kinetic power, demonstrating a steeper functional decline in males (p < 0.001). The neural network achieved 93.2% testing accuracy in classifying spirometric abnormalities. Crucially, Dynamic Airway Collapse Ratio (100% normalized importance), BMI (89.4%), and kinetic power (86.2%) fundamentally outperformed traditional demographic predictors such as chronological age (20.4%) and biological sex (7.1%). Conclusions: Structural and dynamic kinetic factors drive pulmonary dysfunction far more accurately than conventional demographics. Classifying these mechanical phenotypes facilitates highly targeted precision cardiopulmonary rehabilitation. 2026-04-17 ARM, Vol. 94, Pages 26: Biomechanical Phenotyping of Forced Expiration for Precision Pulmonary Rehabilitation: A Machine Learning Approach to Identify Structural and Kinetic Drivers

Advances in Respiratory Medicine doi: 10.3390/arm94020026

Authors: Noppharath Sangkarit Weerasak Tapanya

Background: Standard spirometry fundamentally overlooks the mechanical dynamics of forced expiration. This study derived novel biomechanical parameters to establish functional phenotypes and predict clinical respiratory impairments. Methods: Utilizing 16,596 acceptable spirometry records from NHANES (2007 to 2012), parameters reflecting kinetic power, mass constraint, and airway instability were mathematically derived. Principal component analysis, K-means clustering, and a Multilayer Perceptron neural network were sequentially applied. Results: Three distinct biomechanical phenotypes emerged: Load-Constrained (45.4%), Mechanically Efficient (23.5%), and Dynamic Collapse (31.0%). Aging significantly degraded kinetic power, demonstrating a steeper functional decline in males (p < 0.001). The neural network achieved 93.2% testing accuracy in classifying spirometric abnormalities. Crucially, Dynamic Airway Collapse Ratio (100% normalized importance), BMI (89.4%), and kinetic power (86.2%) fundamentally outperformed traditional demographic predictors such as chronological age (20.4%) and biological sex (7.1%). Conclusions: Structural and dynamic kinetic factors drive pulmonary dysfunction far more accurately than conventional demographics. Classifying these mechanical phenotypes facilitates highly targeted precision cardiopulmonary rehabilitation.

]]> Biomechanical Phenotyping of Forced Expiration for Precision Pulmonary Rehabilitation: A Machine Learning Approach to Identify Structural and Kinetic Drivers Noppharath Sangkarit Weerasak Tapanya doi: 10.3390/arm94020026 Advances in Respiratory Medicine 2026-04-17 Advances in Respiratory Medicine 2026-04-17 94 2 Article 26 10.3390/arm94020026 https://www.mdpi.com/2543-6031/94/2/26 ARM, Vol. 94, Pages 25: Effects of Exercise-Based Pulmonary Rehabilitation in Patients with Long COVID: A Systematic Review and Meta-Analysis https://www.mdpi.com/2543-6031/94/2/25 Background/Objective: A substantial proportion of infected individuals develop persistent symptoms after the acute phase of COVID-19, regardless of initial disease severity. Long COVID (LC) remains a public health challenge characterized by impaired functional exercise capacity (FEC) and quality of life (QoL). We systematically synthesized evidence on the effects of in-person outpatient pulmonary rehabilitation (OPR) with individualized and supervised exercise in adults with LC. Methods: Following PROSPERO (CRD42023389365), this study reviewed randomized controlled trials (RCTs) and observational cohort studies (OCSs) published between November 2019 and January 2026 in MEDLINE/PubMed, Web of Science, PEDro, and EMBASE. Results: Fifteen studies (n = 803) were included. OPR improved FEC (6MWT; MD: 53.72 m, 95% CI 43.69–63.75) and 30″SST (MD: 4.68, 95% CI 3.59–5.77) and reduced exertional dyspnea. RCTs showed benefits in physical (MD: 8.04, 95% CI 3.02–13.05) and mental QoL (MD: 6.60, 95% CI 2.01–11.18) and dyspnea impact, with inconsistent PF findings. Fatigue showed a trend toward improvement but was measured using heterogeneous patient-reported tools in RCTs and OCSs. Conclusions: Supervised PR improves FEC, QoL, and dyspnea in individuals with LC. In patients with fatigue/PEM, systematic assessment and continuous symptom monitoring are essential. High-quality controlled studies are needed to strengthen evidence and clinical guide. 2026-04-10 ARM, Vol. 94, Pages 25: Effects of Exercise-Based Pulmonary Rehabilitation in Patients with Long COVID: A Systematic Review and Meta-Analysis

Advances in Respiratory Medicine doi: 10.3390/arm94020025

Authors: Janne Marques Silveira Ana Paula Midori Nakaishi Marcos Gontijo da Silva Daniele Oliveira dos Santos Ada Clarice Gastaldi

Background/Objective: A substantial proportion of infected individuals develop persistent symptoms after the acute phase of COVID-19, regardless of initial disease severity. Long COVID (LC) remains a public health challenge characterized by impaired functional exercise capacity (FEC) and quality of life (QoL). We systematically synthesized evidence on the effects of in-person outpatient pulmonary rehabilitation (OPR) with individualized and supervised exercise in adults with LC. Methods: Following PROSPERO (CRD42023389365), this study reviewed randomized controlled trials (RCTs) and observational cohort studies (OCSs) published between November 2019 and January 2026 in MEDLINE/PubMed, Web of Science, PEDro, and EMBASE. Results: Fifteen studies (n = 803) were included. OPR improved FEC (6MWT; MD: 53.72 m, 95% CI 43.69–63.75) and 30″SST (MD: 4.68, 95% CI 3.59–5.77) and reduced exertional dyspnea. RCTs showed benefits in physical (MD: 8.04, 95% CI 3.02–13.05) and mental QoL (MD: 6.60, 95% CI 2.01–11.18) and dyspnea impact, with inconsistent PF findings. Fatigue showed a trend toward improvement but was measured using heterogeneous patient-reported tools in RCTs and OCSs. Conclusions: Supervised PR improves FEC, QoL, and dyspnea in individuals with LC. In patients with fatigue/PEM, systematic assessment and continuous symptom monitoring are essential. High-quality controlled studies are needed to strengthen evidence and clinical guide.

]]> Effects of Exercise-Based Pulmonary Rehabilitation in Patients with Long COVID: A Systematic Review and Meta-Analysis Janne Marques Silveira Ana Paula Midori Nakaishi Marcos Gontijo da Silva Daniele Oliveira dos Santos Ada Clarice Gastaldi doi: 10.3390/arm94020025 Advances in Respiratory Medicine 2026-04-10 Advances in Respiratory Medicine 2026-04-10 94 2 Systematic Review 25 10.3390/arm94020025 https://www.mdpi.com/2543-6031/94/2/25 ARM, Vol. 94, Pages 24: Prognostic Impact of Serum Transthyretin and Sarcopenia on 3-Year Mortality and Respiratory-Related Hospitalizations in Idiopathic Pulmonary Fibrosis: A Prospective Cohort Study https://www.mdpi.com/2543-6031/94/2/24 Background: Prognostic markers reflecting nutritional vulnerability in idiopathic pulmonary fibrosis (IPF) remain poorly defined. Methods: In this prospective cohort study, 63 stable outpatients with IPF were followed for 3 years. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia criteria. Serum transthyretin levels were measured concurrently. Cox proportional hazards regression, binary logistic regression, and Kaplan–Meier survival analyses were performed. Results: During follow-up, 18 patients (29%) died and 21 (33%) experienced respiratory-related hospitalization. Serum transthyretin was an independent predictor of both 3-year mortality and respiratory-related hospitalization, even after adjusting for the Gender–Age–Physiology index. Conversely, sarcopenia and low appendicular skeletal muscle mass index (ASMI) were not independently associated with either outcome. Kaplan–Meier analysis demonstrated significant differences in both mortality and hospitalization according to serum transthyretin levels. Low ASMI evaluated using sex-specific cutoffs was associated with higher mortality in the unadjusted analysis, but not with hospitalization; sarcopenia was not significantly associated with either endpoint. Conclusions: Serum transthyretin may serve as a practical biomarker of nutritional vulnerability, providing complementary prognostic information beyond muscle mass-based assessment in IPF. 2026-04-08 ARM, Vol. 94, Pages 24: Prognostic Impact of Serum Transthyretin and Sarcopenia on 3-Year Mortality and Respiratory-Related Hospitalizations in Idiopathic Pulmonary Fibrosis: A Prospective Cohort Study

Advances in Respiratory Medicine doi: 10.3390/arm94020024

Authors: Akihito Okada Akiko Nakano Kohei Fujita Yoshitsugu Inoue Toshiyasu Ito Fumitaka Hashiba Masashi Fujikawa Tatsuya Tanaka Aya Mukai Keima Ito Yuta Mori Kensuke Fukumitsu Satoshi Fukuda Yoshihiro Kanemitsu Tomoko Tajiri Tetsuya Oguri Yoshiyuki Ozawa Takayuki Murase Hirotsugu Ohkubo

Background: Prognostic markers reflecting nutritional vulnerability in idiopathic pulmonary fibrosis (IPF) remain poorly defined. Methods: In this prospective cohort study, 63 stable outpatients with IPF were followed for 3 years. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia criteria. Serum transthyretin levels were measured concurrently. Cox proportional hazards regression, binary logistic regression, and Kaplan–Meier survival analyses were performed. Results: During follow-up, 18 patients (29%) died and 21 (33%) experienced respiratory-related hospitalization. Serum transthyretin was an independent predictor of both 3-year mortality and respiratory-related hospitalization, even after adjusting for the Gender–Age–Physiology index. Conversely, sarcopenia and low appendicular skeletal muscle mass index (ASMI) were not independently associated with either outcome. Kaplan–Meier analysis demonstrated significant differences in both mortality and hospitalization according to serum transthyretin levels. Low ASMI evaluated using sex-specific cutoffs was associated with higher mortality in the unadjusted analysis, but not with hospitalization; sarcopenia was not significantly associated with either endpoint. Conclusions: Serum transthyretin may serve as a practical biomarker of nutritional vulnerability, providing complementary prognostic information beyond muscle mass-based assessment in IPF.

]]> Prognostic Impact of Serum Transthyretin and Sarcopenia on 3-Year Mortality and Respiratory-Related Hospitalizations in Idiopathic Pulmonary Fibrosis: A Prospective Cohort Study Akihito Okada Akiko Nakano Kohei Fujita Yoshitsugu Inoue Toshiyasu Ito Fumitaka Hashiba Masashi Fujikawa Tatsuya Tanaka Aya Mukai Keima Ito Yuta Mori Kensuke Fukumitsu Satoshi Fukuda Yoshihiro Kanemitsu Tomoko Tajiri Tetsuya Oguri Yoshiyuki Ozawa Takayuki Murase Hirotsugu Ohkubo doi: 10.3390/arm94020024 Advances in Respiratory Medicine 2026-04-08 Advances in Respiratory Medicine 2026-04-08 94 2 Article 24 10.3390/arm94020024 https://www.mdpi.com/2543-6031/94/2/24 ARM, Vol. 94, Pages 23: Stroke-Associated Pneumonia and Impaired Functional Recovery After Stroke: The Role of Nutritional-Inflammatory Factors https://www.mdpi.com/2543-6031/94/2/23 Background: Stroke-associated pneumonia (SAP) is a common complication after acute ischemic stroke and contributes to worse recovery and greater resource use. Nutritional and inflammatory dysregulation have been implicated in both SAP susceptibility and adverse prognosis. Objective: To examine whether admission inflammatory and nutritional markers are associated with the development of SAP and with short-term functional prognosis. Methods: We performed a retrospective single-centre cohort study of consecutive patients with acute ischemic stroke admitted between 1 January 2015 and 31 December 2024 (N=303;SAPn=108,non−SAPn=195). Admission laboratory indices (albumin, CRP, fibrinogen, WBC, PCT, and prealbumin) in the first 24 h and clinical variables were analysed. Multivariable logistic regression identified factors independently associated with SAP; the relationship between SAP and early functional recovery was assessed in adjusted outcome models. A nomogram integrating key predictors was developed and its apparent discrimination is reported. Results: SAP occurred in 35.6% of patients. Factors independently associated with SAP included nasogastric tube placement (OR: 7.02, 95% CI: 3.50–14.62), venous thromboembolism (OR: 3.20, 95% CI: 1.62–6.31), cognitive impairment (OR: 2.90, 95% CI: 1.32–6.36), and elevated inflammatory markers (WBC OR: 1.52, 95% CI: 1.28–1.80; fibrinogen OR: 1.37, 95% CI: 1.02–1.84; CRP OR: 1.01, 95% CI: 1.00–1.03). Higher admission serum albumin was associated with lower odds of SAP (OR: 0.92, 95% CI: 0.86–0.98). The nomogram showed strong apparent discrimination (AUC: 0.90, 95% CI: 0.86–0.94). After multivariable adjustment, SAP remained associated with poorer short-term functional improvement (adjusted OR: 6.99, 95% CI: 3.05–17.54) and greater healthcare utilization (median length of stay: 39.6 vs. 30.6 days; median cost: USD 12,836 vs. 6585). Conclusion: In this retrospective cohort, admission markers of nutritional depletion and inflammatory activation were associated not only with increased likelihood of SAP, but also with adverse early functional outcomes. These association-based findings support early risk stratification using routine admission markers; prospective studies and external validation are required before clinical implementation. 2026-04-06 ARM, Vol. 94, Pages 23: Stroke-Associated Pneumonia and Impaired Functional Recovery After Stroke: The Role of Nutritional-Inflammatory Factors

Advances in Respiratory Medicine doi: 10.3390/arm94020023

Authors: Rongjian Feng Chonggui Jiang Yan Yang Mao Su Meng Qin Quan Wei

Background: Stroke-associated pneumonia (SAP) is a common complication after acute ischemic stroke and contributes to worse recovery and greater resource use. Nutritional and inflammatory dysregulation have been implicated in both SAP susceptibility and adverse prognosis. Objective: To examine whether admission inflammatory and nutritional markers are associated with the development of SAP and with short-term functional prognosis. Methods: We performed a retrospective single-centre cohort study of consecutive patients with acute ischemic stroke admitted between 1 January 2015 and 31 December 2024 (N=303;SAPn=108,non−SAPn=195). Admission laboratory indices (albumin, CRP, fibrinogen, WBC, PCT, and prealbumin) in the first 24 h and clinical variables were analysed. Multivariable logistic regression identified factors independently associated with SAP; the relationship between SAP and early functional recovery was assessed in adjusted outcome models. A nomogram integrating key predictors was developed and its apparent discrimination is reported. Results: SAP occurred in 35.6% of patients. Factors independently associated with SAP included nasogastric tube placement (OR: 7.02, 95% CI: 3.50–14.62), venous thromboembolism (OR: 3.20, 95% CI: 1.62–6.31), cognitive impairment (OR: 2.90, 95% CI: 1.32–6.36), and elevated inflammatory markers (WBC OR: 1.52, 95% CI: 1.28–1.80; fibrinogen OR: 1.37, 95% CI: 1.02–1.84; CRP OR: 1.01, 95% CI: 1.00–1.03). Higher admission serum albumin was associated with lower odds of SAP (OR: 0.92, 95% CI: 0.86–0.98). The nomogram showed strong apparent discrimination (AUC: 0.90, 95% CI: 0.86–0.94). After multivariable adjustment, SAP remained associated with poorer short-term functional improvement (adjusted OR: 6.99, 95% CI: 3.05–17.54) and greater healthcare utilization (median length of stay: 39.6 vs. 30.6 days; median cost: USD 12,836 vs. 6585). Conclusion: In this retrospective cohort, admission markers of nutritional depletion and inflammatory activation were associated not only with increased likelihood of SAP, but also with adverse early functional outcomes. These association-based findings support early risk stratification using routine admission markers; prospective studies and external validation are required before clinical implementation.

]]> Stroke-Associated Pneumonia and Impaired Functional Recovery After Stroke: The Role of Nutritional-Inflammatory Factors Rongjian Feng Chonggui Jiang Yan Yang Mao Su Meng Qin Quan Wei doi: 10.3390/arm94020023 Advances in Respiratory Medicine 2026-04-06 Advances in Respiratory Medicine 2026-04-06 94 2 Article 23 10.3390/arm94020023 https://www.mdpi.com/2543-6031/94/2/23 ARM, Vol. 94, Pages 22: Non-Pharmacological Pulmonary Rehabilitation in Patients with Pneumoconiosis: A Systematic Review https://www.mdpi.com/2543-6031/94/2/22 Background: Pneumoconiosis remains a major occupational lung disease associated with progressive respiratory impairment, reduced functional capacity, and diminished quality of life. Non-pharmacological rehabilitation has been increasingly proposed as a supportive intervention; however, evidence regarding its effectiveness remains heterogeneous. Objective: This study aimed to systematically review and synthesize the available evidence on the effects of non-pharmacological rehabilitation interventions on functional capacity, quality of life, and psychological outcomes in patients with pneumoconiosis. Methods: A systematic literature search was conducted in major electronic databases and grey literature sources in accordance with PRISMA 2020 guidelines. Studies evaluating non-pharmacological rehabilitation interventions in adults with pneumoconiosis were eligible for inclusion. Outcomes of interest included functional capacity, health-related quality of life, and psychological well-being. Due to methodological heterogeneity across studies, a qualitative synthesis was performed. Results: Six studies met the predefined inclusion criteria and were included in the qualitative synthesis. The reviewed evidence suggests that structured rehabilitation interventions were associated with clinically meaningful improvements in functional capacity, particularly in structured rehabilitation programs, most consistently reflected by increases in six-minute walk distance exceeding established minimal clinically important differences in three studies. Improvements in health-related quality of life and selected psychological outcomes were also reported, although outcome measures and intervention protocols varied across studies. Significant improvements in exercise capacity, dyspnea severity, and health-related quality of life were reported. Conclusions: Non-pharmacological rehabilitation may provide clinically meaningful benefits for patients with pneumoconiosis, based on limited and heterogeneous evidence, particularly in terms of functional capacity and quality of life. Nevertheless, the current evidence base is limited by heterogeneity in study design and outcome reporting. Further high-quality, standardized trials are needed to strengthen the evidence and guide the clinical implementation of rehabilitation programs for occupational lung diseases. 2026-03-31 ARM, Vol. 94, Pages 22: Non-Pharmacological Pulmonary Rehabilitation in Patients with Pneumoconiosis: A Systematic Review

Advances in Respiratory Medicine doi: 10.3390/arm94020022

Authors: Madina B. Baurzhan Sayagul A. Kairgeldina Venera M. Almatova Alexandr E. Gulyayev Raushan S. Dosmagambetova Kanat K. Tekebayev Karashash Absatarova Karlygash S. Absattarova

Background: Pneumoconiosis remains a major occupational lung disease associated with progressive respiratory impairment, reduced functional capacity, and diminished quality of life. Non-pharmacological rehabilitation has been increasingly proposed as a supportive intervention; however, evidence regarding its effectiveness remains heterogeneous. Objective: This study aimed to systematically review and synthesize the available evidence on the effects of non-pharmacological rehabilitation interventions on functional capacity, quality of life, and psychological outcomes in patients with pneumoconiosis. Methods: A systematic literature search was conducted in major electronic databases and grey literature sources in accordance with PRISMA 2020 guidelines. Studies evaluating non-pharmacological rehabilitation interventions in adults with pneumoconiosis were eligible for inclusion. Outcomes of interest included functional capacity, health-related quality of life, and psychological well-being. Due to methodological heterogeneity across studies, a qualitative synthesis was performed. Results: Six studies met the predefined inclusion criteria and were included in the qualitative synthesis. The reviewed evidence suggests that structured rehabilitation interventions were associated with clinically meaningful improvements in functional capacity, particularly in structured rehabilitation programs, most consistently reflected by increases in six-minute walk distance exceeding established minimal clinically important differences in three studies. Improvements in health-related quality of life and selected psychological outcomes were also reported, although outcome measures and intervention protocols varied across studies. Significant improvements in exercise capacity, dyspnea severity, and health-related quality of life were reported. Conclusions: Non-pharmacological rehabilitation may provide clinically meaningful benefits for patients with pneumoconiosis, based on limited and heterogeneous evidence, particularly in terms of functional capacity and quality of life. Nevertheless, the current evidence base is limited by heterogeneity in study design and outcome reporting. Further high-quality, standardized trials are needed to strengthen the evidence and guide the clinical implementation of rehabilitation programs for occupational lung diseases.

]]> Non-Pharmacological Pulmonary Rehabilitation in Patients with Pneumoconiosis: A Systematic Review Madina B. Baurzhan Sayagul A. Kairgeldina Venera M. Almatova Alexandr E. Gulyayev Raushan S. Dosmagambetova Kanat K. Tekebayev Karashash Absatarova Karlygash S. Absattarova doi: 10.3390/arm94020022 Advances in Respiratory Medicine 2026-03-31 Advances in Respiratory Medicine 2026-03-31 94 2 Article 22 10.3390/arm94020022 https://www.mdpi.com/2543-6031/94/2/22 ARM, Vol. 94, Pages 21: High-Flow Nasal Cannula in Patients Awaiting Lung Transplant: Evidence, Clinical Applications, and Outcomes https://www.mdpi.com/2543-6031/94/2/21 Patients with end-stage lung diseases awaiting lung transplant frequently experience severe hypoxemia, dyspnea, and functional limitations that may compromise survival and transplant eligibility. Optimizing noninvasive respiratory support during the waiting period is crucial to preserve oxygenation, maintain physical conditioning, and avoid escalation to invasive mechanical ventilation, which is associated with poorer transplant outcomes. High-flow nasal cannula therapy has emerged as an important noninvasive respiratory support modality capable of providing physiological and clinical benefits such as precise fractions of inspired oxygen, a low level of positive end-expiratory pressure, dead-space washout, and reduced work of breathing. This review summarizes the pathophysiology of hypoxemia in lung transplant candidates, the mechanisms of action of high-flow nasal cannulas, and the current clinical evidence supporting its use in this population during the pre-transplant period. Available evidence suggests that the use of high-flow nasal cannulas improves oxygenation, relieves dyspnea, enhances exercise tolerance, facilitates participation in pulmonary rehabilitation programs, and may reduce the need for endotracheal intubation, thereby improving the likelihood of survival to transplantation. The review also discusses patient selection, the practical implementation of high-flow nasal cannula therapy, and comparisons with other respiratory support modalities. Although the current evidence is largely observational and heterogenous, high flow appears to be a valuable supportive and bridging therapy for selected patients awaiting lung transplant. Future prospective studies are needed to define standardized protocols and evaluate transplant-specific outcomes. 2026-03-30 ARM, Vol. 94, Pages 21: High-Flow Nasal Cannula in Patients Awaiting Lung Transplant: Evidence, Clinical Applications, and Outcomes

Advances in Respiratory Medicine doi: 10.3390/arm94020021

Authors: Salah M. Zeineldine Rami Hallak Antonio Esquinas Mohamad F. El-Khatib

Patients with end-stage lung diseases awaiting lung transplant frequently experience severe hypoxemia, dyspnea, and functional limitations that may compromise survival and transplant eligibility. Optimizing noninvasive respiratory support during the waiting period is crucial to preserve oxygenation, maintain physical conditioning, and avoid escalation to invasive mechanical ventilation, which is associated with poorer transplant outcomes. High-flow nasal cannula therapy has emerged as an important noninvasive respiratory support modality capable of providing physiological and clinical benefits such as precise fractions of inspired oxygen, a low level of positive end-expiratory pressure, dead-space washout, and reduced work of breathing. This review summarizes the pathophysiology of hypoxemia in lung transplant candidates, the mechanisms of action of high-flow nasal cannulas, and the current clinical evidence supporting its use in this population during the pre-transplant period. Available evidence suggests that the use of high-flow nasal cannulas improves oxygenation, relieves dyspnea, enhances exercise tolerance, facilitates participation in pulmonary rehabilitation programs, and may reduce the need for endotracheal intubation, thereby improving the likelihood of survival to transplantation. The review also discusses patient selection, the practical implementation of high-flow nasal cannula therapy, and comparisons with other respiratory support modalities. Although the current evidence is largely observational and heterogenous, high flow appears to be a valuable supportive and bridging therapy for selected patients awaiting lung transplant. Future prospective studies are needed to define standardized protocols and evaluate transplant-specific outcomes.

]]> High-Flow Nasal Cannula in Patients Awaiting Lung Transplant: Evidence, Clinical Applications, and Outcomes Salah M. Zeineldine Rami Hallak Antonio Esquinas Mohamad F. El-Khatib doi: 10.3390/arm94020021 Advances in Respiratory Medicine 2026-03-30 Advances in Respiratory Medicine 2026-03-30 94 2 Review 21 10.3390/arm94020021 https://www.mdpi.com/2543-6031/94/2/21 ARM, Vol. 94, Pages 20: Glucagon-like Peptide-1 Receptor Agonist Therapy and Risk of Pulmonary and Systemic Infections in Diabetic Gastroparesis: A Propensity-Matched Cohort Study https://www.mdpi.com/2543-6031/94/2/20 Introduction: Diabetic gastroparesis increases the risk of aspiration, pneumonia, and sepsis, yet the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on these outcomes is uncertain because of their gastric-emptying effects. Methods: We performed a retrospective cohort study using the TriNetX Global Research Network. Adults (≥18 years) with diabetes mellitus and gastroparesis were identified and divided into two cohorts based on GLP-1 RA exposure. Propensity score matching (1:1) balanced demographics, comorbidities, and antidiabetic medications, yielding 23,371 patients per cohort. Outcomes, assessed from 180 days after index, included pneumonia, pneumonitis, mechanical ventilation, ventilator-associated pneumonia, sepsis, bacteremia, empyema, lung abscess, acute respiratory distress syndrome (ARDS), and need for enteral feeding. Risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Results: Compared with GLP-1 users, non-GLP-1 patients had higher incidences of pneumonitis (3.6% vs. 2.5%; HR 1.76, 95% CI 1.58–1.95), pneumonia (13.2% vs. 12.2%; HR 1.34, 95% CI 1.27–1.41), mechanical ventilation (4.4% vs. 3.3%; HR 1.63, 95% CI 1.49–1.79), sepsis (12.8% vs. 11.1%; HR 1.44, 95% CI 1.37–1.52), and bacteremia (5.2% vs. 4.4%; HR 1.46, 95% CI 1.35–1.59) (all p < 0.001). Empyema and ARDS were also numerically lower among GLP-1 users, while ventilator-associated pneumonia and lung abscess were rare and similar between groups. No patients required percutaneous endoscopic gastrostomy or nasal enteral feeding. Conclusions: In patients with diabetes and gastroparesis, GLP-1 RA therapy was associated with significantly fewer pulmonary and systemic infectious complications. These data suggest that the systemic benefits of GLP-1 RAs may outweigh concerns regarding delayed gastric emptying in this high-risk population. 2026-03-24 ARM, Vol. 94, Pages 20: Glucagon-like Peptide-1 Receptor Agonist Therapy and Risk of Pulmonary and Systemic Infections in Diabetic Gastroparesis: A Propensity-Matched Cohort Study

Advances in Respiratory Medicine doi: 10.3390/arm94020020

Authors: Muhammad Ali Ibrahim Kazi Hasan Kamal Syed Musa Mufarrih Imran Qureshi Sanmeet Singh Adrien Mazer

Introduction: Diabetic gastroparesis increases the risk of aspiration, pneumonia, and sepsis, yet the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on these outcomes is uncertain because of their gastric-emptying effects. Methods: We performed a retrospective cohort study using the TriNetX Global Research Network. Adults (≥18 years) with diabetes mellitus and gastroparesis were identified and divided into two cohorts based on GLP-1 RA exposure. Propensity score matching (1:1) balanced demographics, comorbidities, and antidiabetic medications, yielding 23,371 patients per cohort. Outcomes, assessed from 180 days after index, included pneumonia, pneumonitis, mechanical ventilation, ventilator-associated pneumonia, sepsis, bacteremia, empyema, lung abscess, acute respiratory distress syndrome (ARDS), and need for enteral feeding. Risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated. Results: Compared with GLP-1 users, non-GLP-1 patients had higher incidences of pneumonitis (3.6% vs. 2.5%; HR 1.76, 95% CI 1.58–1.95), pneumonia (13.2% vs. 12.2%; HR 1.34, 95% CI 1.27–1.41), mechanical ventilation (4.4% vs. 3.3%; HR 1.63, 95% CI 1.49–1.79), sepsis (12.8% vs. 11.1%; HR 1.44, 95% CI 1.37–1.52), and bacteremia (5.2% vs. 4.4%; HR 1.46, 95% CI 1.35–1.59) (all p < 0.001). Empyema and ARDS were also numerically lower among GLP-1 users, while ventilator-associated pneumonia and lung abscess were rare and similar between groups. No patients required percutaneous endoscopic gastrostomy or nasal enteral feeding. Conclusions: In patients with diabetes and gastroparesis, GLP-1 RA therapy was associated with significantly fewer pulmonary and systemic infectious complications. These data suggest that the systemic benefits of GLP-1 RAs may outweigh concerns regarding delayed gastric emptying in this high-risk population.

]]> Glucagon-like Peptide-1 Receptor Agonist Therapy and Risk of Pulmonary and Systemic Infections in Diabetic Gastroparesis: A Propensity-Matched Cohort Study Muhammad Ali Ibrahim Kazi Hasan Kamal Syed Musa Mufarrih Imran Qureshi Sanmeet Singh Adrien Mazer doi: 10.3390/arm94020020 Advances in Respiratory Medicine 2026-03-24 Advances in Respiratory Medicine 2026-03-24 94 2 Article 20 10.3390/arm94020020 https://www.mdpi.com/2543-6031/94/2/20 ARM, Vol. 94, Pages 19: Diagnostic Factors Associated with Sarcoidosis in Patients Referred for EBUS-TBNA Due to Mediastinal Lymphadenopathy https://www.mdpi.com/2543-6031/94/2/19 Sarcoidosis is a multisystem granulomatous disease of unknown aetiology that frequently presents with mediastinal lymphadenopathy and often requires invasive diagnostic procedures. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used in this setting; however, a definitive diagnosis cannot always be established at first attempt. This study aimed to identify clinical, laboratory, and radiological factors associated with a definitive diagnosis of sarcoidosis in patients referred for EBUS-TBNA. A retrospective analysis was performed including patients undergoing first-time ever EBUS-TBNA for mediastinal lymphadenopathy over a 12-month period. Demographic data, clinical features suggestive of sarcoidosis, chest computed tomography findings, and white blood cell count, were analysed, and definitive diagnoses were established based on cytological results and available follow-up data. Younger age (≤55 years), female sex, the absence of a pulmonary mass >10 mm on imaging, normal white blood cell count, and the presence of clinical features typical of sarcoidosis were significantly associated with a definitive diagnosis of sarcoidosis. Based on these variables, two point-based diagnostic scoring models were developed, demonstrating clinically relevant discriminatory performance. Readily available pre-procedural clinical and radiological factors may assist in estimating the probability of sarcoidosis in patients undergoing EBUS-TBNA for mediastinal lymphadenopathy and may support risk stratification and clinical decision-making. 2026-03-16 ARM, Vol. 94, Pages 19: Diagnostic Factors Associated with Sarcoidosis in Patients Referred for EBUS-TBNA Due to Mediastinal Lymphadenopathy

Advances in Respiratory Medicine doi: 10.3390/arm94020019

Authors: Paweł Zając Monika Zając Wojciech Kądziołka Andrzej Sokołowski Ewa Kaznowska

Sarcoidosis is a multisystem granulomatous disease of unknown aetiology that frequently presents with mediastinal lymphadenopathy and often requires invasive diagnostic procedures. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used in this setting; however, a definitive diagnosis cannot always be established at first attempt. This study aimed to identify clinical, laboratory, and radiological factors associated with a definitive diagnosis of sarcoidosis in patients referred for EBUS-TBNA. A retrospective analysis was performed including patients undergoing first-time ever EBUS-TBNA for mediastinal lymphadenopathy over a 12-month period. Demographic data, clinical features suggestive of sarcoidosis, chest computed tomography findings, and white blood cell count, were analysed, and definitive diagnoses were established based on cytological results and available follow-up data. Younger age (≤55 years), female sex, the absence of a pulmonary mass >10 mm on imaging, normal white blood cell count, and the presence of clinical features typical of sarcoidosis were significantly associated with a definitive diagnosis of sarcoidosis. Based on these variables, two point-based diagnostic scoring models were developed, demonstrating clinically relevant discriminatory performance. Readily available pre-procedural clinical and radiological factors may assist in estimating the probability of sarcoidosis in patients undergoing EBUS-TBNA for mediastinal lymphadenopathy and may support risk stratification and clinical decision-making.

]]> Diagnostic Factors Associated with Sarcoidosis in Patients Referred for EBUS-TBNA Due to Mediastinal Lymphadenopathy Paweł Zając Monika Zając Wojciech Kądziołka Andrzej Sokołowski Ewa Kaznowska doi: 10.3390/arm94020019 Advances in Respiratory Medicine 2026-03-16 Advances in Respiratory Medicine 2026-03-16 94 2 Article 19 10.3390/arm94020019 https://www.mdpi.com/2543-6031/94/2/19 ARM, Vol. 94, Pages 18: Clues to Long COVID Linked to Virulence and Infectivity Found in Shell Proteins https://www.mdpi.com/2543-6031/94/2/18 Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2—but not in SARS-CoV-1—as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein–protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus. 2026-03-11 ARM, Vol. 94, Pages 18: Clues to Long COVID Linked to Virulence and Infectivity Found in Shell Proteins

Advances in Respiratory Medicine doi: 10.3390/arm94020018

Authors: Gerard Kian-Meng Goh James A. Foster Vladimir N. Uversky

Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2—but not in SARS-CoV-1—as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein–protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus.

]]> Clues to Long COVID Linked to Virulence and Infectivity Found in Shell Proteins Gerard Kian-Meng Goh James A. Foster Vladimir N. Uversky doi: 10.3390/arm94020018 Advances in Respiratory Medicine 2026-03-11 Advances in Respiratory Medicine 2026-03-11 94 2 Review 18 10.3390/arm94020018 https://www.mdpi.com/2543-6031/94/2/18 ARM, Vol. 94, Pages 17: Safety of Performing Spirometry During Pregnancy: A Systematic Review https://www.mdpi.com/2543-6031/94/2/17 Introduction: It is estimated that up to 75% of pregnant women complain of dyspnea at some point during pregnancy. Asthma is the most common chronic pulmonary disease complicating pregnancy. Well controlled asthma does not affect pregnancy negatively. However, asthma exacerbations are linked with several adverse perinatal outcomes. As diligent treatment of asthma significantly reduces the number of asthma exacerbations, it is important to properly detect asthmatic patients among pregnant women in order to provide them with better care. The most efficient way to diagnose asthma is to perform spirometry with a reversibility test. There are no studies that have examined the safety of performing spirometry and, more specifically, a reversibility test, during pregnancy. Objectives: In this systematic review we aimed to review current available data regarding the safety of performing spirometry and a reversibility test during pregnancy. Patients and methods: For this systematic review, we searched PubMed, Scopus and Cochrane databases. We used the following search terms: (pregnancy); (spirometry); (lung function test); (pulmonary function test); (reversibility test); (post-bronchodilator challenge); (safety). Results: We collected reports of spirometry performed on pregnant women and analyzed them for complications that occurred during the procedure. Out of 13,594 records identified for the aforementioned search words, we included 78 documents that met the inclusion criteria. In total, the studies consisted of over 33,405 spirometry attempts performed by 10,617 pregnant women. Additionally, the reversibility test was conducted in nine studies. In all of the selected articles, there were no reports of adverse events occurring while performing spirometry. Conclusions: In this systematic review we aimed to summarize the current available data about the safety of performing spirometry during pregnancy. Several studies have investigated pulmonary function tests during pregnancy. No studies reported any adverse events that occurred while performing the procedure. In order to better characterize the safety profile of spirometry, including during pregnancy, further prospective studies systematically reporting on adverse symptoms during spirometry are required. 2026-03-06 ARM, Vol. 94, Pages 17: Safety of Performing Spirometry During Pregnancy: A Systematic Review

Advances in Respiratory Medicine doi: 10.3390/arm94020017

Authors: Zofia Potocka Katarzyna Górska Radosław Ciesielski Dorota Bomba-Opoń Mirosław Wielgoś Piotr Korczyński

Introduction: It is estimated that up to 75% of pregnant women complain of dyspnea at some point during pregnancy. Asthma is the most common chronic pulmonary disease complicating pregnancy. Well controlled asthma does not affect pregnancy negatively. However, asthma exacerbations are linked with several adverse perinatal outcomes. As diligent treatment of asthma significantly reduces the number of asthma exacerbations, it is important to properly detect asthmatic patients among pregnant women in order to provide them with better care. The most efficient way to diagnose asthma is to perform spirometry with a reversibility test. There are no studies that have examined the safety of performing spirometry and, more specifically, a reversibility test, during pregnancy. Objectives: In this systematic review we aimed to review current available data regarding the safety of performing spirometry and a reversibility test during pregnancy. Patients and methods: For this systematic review, we searched PubMed, Scopus and Cochrane databases. We used the following search terms: (pregnancy); (spirometry); (lung function test); (pulmonary function test); (reversibility test); (post-bronchodilator challenge); (safety). Results: We collected reports of spirometry performed on pregnant women and analyzed them for complications that occurred during the procedure. Out of 13,594 records identified for the aforementioned search words, we included 78 documents that met the inclusion criteria. In total, the studies consisted of over 33,405 spirometry attempts performed by 10,617 pregnant women. Additionally, the reversibility test was conducted in nine studies. In all of the selected articles, there were no reports of adverse events occurring while performing spirometry. Conclusions: In this systematic review we aimed to summarize the current available data about the safety of performing spirometry during pregnancy. Several studies have investigated pulmonary function tests during pregnancy. No studies reported any adverse events that occurred while performing the procedure. In order to better characterize the safety profile of spirometry, including during pregnancy, further prospective studies systematically reporting on adverse symptoms during spirometry are required.

]]> Safety of Performing Spirometry During Pregnancy: A Systematic Review Zofia Potocka Katarzyna Górska Radosław Ciesielski Dorota Bomba-Opoń Mirosław Wielgoś Piotr Korczyński doi: 10.3390/arm94020017 Advances in Respiratory Medicine 2026-03-06 Advances in Respiratory Medicine 2026-03-06 94 2 Systematic Review 17 10.3390/arm94020017 https://www.mdpi.com/2543-6031/94/2/17 ARM, Vol. 94, Pages 16: Reply to Dolu, K.O. Comment on “Topaloglu et al. Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis. Adv. Respir. Med. 2025, 93, 32” https://www.mdpi.com/2543-6031/94/2/16 Thank you for forwarding the external comment regarding our published article (Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis) [...] 2026-02-28 ARM, Vol. 94, Pages 16: Reply to Dolu, K.O. Comment on “Topaloglu et al. Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis. Adv. Respir. Med. 2025, 93, 32”

Advances in Respiratory Medicine doi: 10.3390/arm94020016

Authors: Ihsan Topaloglu Gulfem Ozduygu Cagri Atasoy Guntug Batıhan Damla Serce Gulsah Inanc Mutlu Onur Güçsav Arif Metehan Yıldız Turker Tuncer Sengul Dogan Prabal Datta Barua

Thank you for forwarding the external comment regarding our published article (Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis) [...]

]]> Reply to Dolu, K.O. Comment on “Topaloglu et al. Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis. Adv. Respir. Med. 2025, 93, 32” Ihsan Topaloglu Gulfem Ozduygu Cagri Atasoy Guntug Batıhan Damla Serce Gulsah Inanc Mutlu Onur Güçsav Arif Metehan Yıldız Turker Tuncer Sengul Dogan Prabal Datta Barua doi: 10.3390/arm94020016 Advances in Respiratory Medicine 2026-02-28 Advances in Respiratory Medicine 2026-02-28 94 2 Reply 16 10.3390/arm94020016 https://www.mdpi.com/2543-6031/94/2/16 ARM, Vol. 94, Pages 15: Comment on Topaloglu et al. Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis. Adv. Respir. Med. 2025, 93, 32 https://www.mdpi.com/2543-6031/94/2/15 I am writing regarding the article titled “Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis” published by Topaloglu et al [...] 2026-02-28 ARM, Vol. 94, Pages 15: Comment on Topaloglu et al. Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis. Adv. Respir. Med. 2025, 93, 32

Advances in Respiratory Medicine doi: 10.3390/arm94020015

Authors: Kazim Okan Dolu

I am writing regarding the article titled “Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis” published by Topaloglu et al [...]

]]> Comment on Topaloglu et al. Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis. Adv. Respir. Med. 2025, 93, 32 Kazim Okan Dolu doi: 10.3390/arm94020015 Advances in Respiratory Medicine 2026-02-28 Advances in Respiratory Medicine 2026-02-28 94 2 Comment 15 10.3390/arm94020015 https://www.mdpi.com/2543-6031/94/2/15 ARM, Vol. 94, Pages 14: Impact of Dupilumab on Small Airway Disease in Severe Asthma: A 12-Month Retrospective Real-World Study https://www.mdpi.com/2543-6031/94/2/14 Small-airway disease (SAD) is a key feature of severe asthma and is associated with poor symptom control and frequent exacerbations. Dupilumab has demonstrated efficacy in improving lung function and reducing exacerbations, but real-world evidence on its effects in SAD remains limited. The aim of this study is to evaluate the impact of 12 months of dupilumab treatment on SAD, clinical outcomes, and type 2 inflammation. We included 21 patients. Small-airway function was assessed by impulse oscillometry (R5–R20) and spirometry FEF25–75% predicted at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment. Additional assessments included FEV1, the Asthma Control Test (ACT), exacerbation frequency, oral corticosteroid (OCS) use, the blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO). At baseline, 62% of patients exhibited SAD (R5–R20 > 0.07 kPa/L/s). Dupilumab treatment led to a significant and sustained improvement in small-airway function: mean R5–R20 decreased from 0.18 ± 0.17 kPa/L/s to 0.09 ± 0.07 at T12 (p = 0.04), while predicted FEF25–75% increased from 29.5 ± 20.8% to 47.0 ± 21.1% (p < 0.001). ACT scores improved from 13.1 ± 4.9 to 19.6 ± 3.8 (p < 0.001). FeNO levels declined from 64.1 ± 50.7 ppb to 24.8 ± 20.9 ppb (p = 0.01). Improvements in R5–R20 correlated with better ACT and FeNO reductions. In this real-world cohort, dupilumab significantly improved SAD, lung function, and asthma control, while reducing exacerbations, OCS dependence, and type 2 inflammation over 12 months. 2026-02-26 ARM, Vol. 94, Pages 14: Impact of Dupilumab on Small Airway Disease in Severe Asthma: A 12-Month Retrospective Real-World Study

Advances in Respiratory Medicine doi: 10.3390/arm94020014

Authors: Lorenzo Carriera Angelo Coppola Roberto Lipsi Stefano Baglioni Pier-Valerio Mari Roberto Barone Simone Ielo Raffaele Scala Andrea Smargiassi Riccardo Inchingolo Luca Richeldi Valeria Gambacorta Alfredo Di Giovanni Eugenio De Corso

Small-airway disease (SAD) is a key feature of severe asthma and is associated with poor symptom control and frequent exacerbations. Dupilumab has demonstrated efficacy in improving lung function and reducing exacerbations, but real-world evidence on its effects in SAD remains limited. The aim of this study is to evaluate the impact of 12 months of dupilumab treatment on SAD, clinical outcomes, and type 2 inflammation. We included 21 patients. Small-airway function was assessed by impulse oscillometry (R5–R20) and spirometry FEF25–75% predicted at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment. Additional assessments included FEV1, the Asthma Control Test (ACT), exacerbation frequency, oral corticosteroid (OCS) use, the blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO). At baseline, 62% of patients exhibited SAD (R5–R20 > 0.07 kPa/L/s). Dupilumab treatment led to a significant and sustained improvement in small-airway function: mean R5–R20 decreased from 0.18 ± 0.17 kPa/L/s to 0.09 ± 0.07 at T12 (p = 0.04), while predicted FEF25–75% increased from 29.5 ± 20.8% to 47.0 ± 21.1% (p < 0.001). ACT scores improved from 13.1 ± 4.9 to 19.6 ± 3.8 (p < 0.001). FeNO levels declined from 64.1 ± 50.7 ppb to 24.8 ± 20.9 ppb (p = 0.01). Improvements in R5–R20 correlated with better ACT and FeNO reductions. In this real-world cohort, dupilumab significantly improved SAD, lung function, and asthma control, while reducing exacerbations, OCS dependence, and type 2 inflammation over 12 months.

]]> Impact of Dupilumab on Small Airway Disease in Severe Asthma: A 12-Month Retrospective Real-World Study Lorenzo Carriera Angelo Coppola Roberto Lipsi Stefano Baglioni Pier-Valerio Mari Roberto Barone Simone Ielo Raffaele Scala Andrea Smargiassi Riccardo Inchingolo Luca Richeldi Valeria Gambacorta Alfredo Di Giovanni Eugenio De Corso doi: 10.3390/arm94020014 Advances in Respiratory Medicine 2026-02-26 Advances in Respiratory Medicine 2026-02-26 94 2 Article 14 10.3390/arm94020014 https://www.mdpi.com/2543-6031/94/2/14 ARM, Vol. 94, Pages 13: Evaluating the Impact of Inspiratory Muscle Training on Respiratory Function and Exercise Capacity in Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials https://www.mdpi.com/2543-6031/94/1/13 (1) Background: Pulmonary hypertension (PH) is characterized by respiratory muscle weakness, limited exercise tolerance, and reduced quality of life, but inspiratory muscle training (IMT) has emerged as a potential non-pharmacological strategy to improve functional outcomes in this population. This systematic review and meta-analysis evaluated the effects of isolated IMT on respiratory function, exercise capacity, symptom burden, and safety in adults with PH. (2) Methods: A systematic search was conducted in accordance with PRISMA guidelines. Randomized controlled trials involving adults with PH who underwent isolated IMT were included, and respiratory muscle strength, spirometric parameters, exercise capacity, dyspnea, fatigue, quality of life, and adverse events were the outcomes that were assessed. Data were pooled using meta-analytic techniques where appropriate. (3) Results: A total of 130 participants, assigned to five randomized controlled trials, met the inclusion criteria. IMT significantly improved maximal inspiratory pressure (MD = +24.01 cmH2O), maximal expiratory pressure (MD = +23.64 cmH2O), and six-minute walk distance (MD = +60.61 m), but no significant changes were observed in spirometric indices (FEV1%, FVC%, and FEV1/FVC). While several individual studies demonstrated clinically relevant improvements in six-minute walk distance, the pooled analysis did not demonstrate a statistically significant effect. IMT consistently reduced dyspnea and fatigue and improved quality-of-life domains. No serious adverse events were reported, and adherence was high. (4) Conclusions: IMT is a safe and feasible adjunct intervention in PH, providing meaningful improvements in respiratory muscle strength and symptom burden. Further large-scale trials are warranted to confirm its long-term clinical benefits. 2026-02-15 ARM, Vol. 94, Pages 13: Evaluating the Impact of Inspiratory Muscle Training on Respiratory Function and Exercise Capacity in Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Advances in Respiratory Medicine doi: 10.3390/arm94010013

Authors: Saja Alrashedi Lama Alharbi Meshal Alotaibi Inad Alzahrani Albara Jad Qamar Aldoboke Suroor Algethami Raghda Alrabah Rana Alharbi Ali Al Nuwaiser Mohammed Al-Hariri

(1) Background: Pulmonary hypertension (PH) is characterized by respiratory muscle weakness, limited exercise tolerance, and reduced quality of life, but inspiratory muscle training (IMT) has emerged as a potential non-pharmacological strategy to improve functional outcomes in this population. This systematic review and meta-analysis evaluated the effects of isolated IMT on respiratory function, exercise capacity, symptom burden, and safety in adults with PH. (2) Methods: A systematic search was conducted in accordance with PRISMA guidelines. Randomized controlled trials involving adults with PH who underwent isolated IMT were included, and respiratory muscle strength, spirometric parameters, exercise capacity, dyspnea, fatigue, quality of life, and adverse events were the outcomes that were assessed. Data were pooled using meta-analytic techniques where appropriate. (3) Results: A total of 130 participants, assigned to five randomized controlled trials, met the inclusion criteria. IMT significantly improved maximal inspiratory pressure (MD = +24.01 cmH2O), maximal expiratory pressure (MD = +23.64 cmH2O), and six-minute walk distance (MD = +60.61 m), but no significant changes were observed in spirometric indices (FEV1%, FVC%, and FEV1/FVC). While several individual studies demonstrated clinically relevant improvements in six-minute walk distance, the pooled analysis did not demonstrate a statistically significant effect. IMT consistently reduced dyspnea and fatigue and improved quality-of-life domains. No serious adverse events were reported, and adherence was high. (4) Conclusions: IMT is a safe and feasible adjunct intervention in PH, providing meaningful improvements in respiratory muscle strength and symptom burden. Further large-scale trials are warranted to confirm its long-term clinical benefits.

]]> Evaluating the Impact of Inspiratory Muscle Training on Respiratory Function and Exercise Capacity in Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Saja Alrashedi Lama Alharbi Meshal Alotaibi Inad Alzahrani Albara Jad Qamar Aldoboke Suroor Algethami Raghda Alrabah Rana Alharbi Ali Al Nuwaiser Mohammed Al-Hariri doi: 10.3390/arm94010013 Advances in Respiratory Medicine 2026-02-15 Advances in Respiratory Medicine 2026-02-15 94 1 Systematic Review 13 10.3390/arm94010013 https://www.mdpi.com/2543-6031/94/1/13 ARM, Vol. 94, Pages 12: Trend Analysis of Respiratory Disease Mortality in the Population Aged 65 and over in Poland: Results from a Registry Study (2000–2022) https://www.mdpi.com/2543-6031/94/1/12 Background: Respiratory diseases remain a major contributor to mortality in Europe, yet national long-term analyses rarely explore sex- and age-specific temporal patterns in detail. Large international datasets provide aggregated estimates but may obscure country-specific trend changes relevant for public health planning. The aim of the study was to assess long-term trends in mortality from chronic lower respiratory diseases (ICD-10: J40–J47) as well as pneumonia and influenza. (ICD-10: J10–J18) in Poland, with particular emphasis on sex- and age-specific trajectories and joinpoint-defined changes over time. Methods: All deaths among Polish residents aged ≥65 years were analysed using nationwide mortality registry data. Age-standardised death rates (SDRs) were calculated, and temporal trends were assessed using joinpoint regression models to estimate annual percentage changes (APC) and average annual percentage change (AAPC). Results: The proportion of deaths attributable to respiratory diseases increased in both men and women across early (65–74 years) and late (≥75 years) old age. Mortality from chronic lower respiratory diseases declined throughout the study period among men, with the most pronounced reductions observed in the early 2000s, particularly among those aged ≥75 years, while trends among women remained largely stable or showed only gradual declines. In contrast, mortality from pneumonia and influenza rose markedly across all sex and age subgroups, with distinct trend reversals observed after 2008–2009. Conclusions: Long-term respiratory mortality trends in Poland exhibit marked sex- and age-specific differences that are not fully captured by aggregated international analyses. These findings highlight the importance of country-level, stratified assessments when interpreting respiratory mortality patterns and underscore the need for caution when relying on single time-point indicators for risk assessment and policy planning. 2026-02-14 ARM, Vol. 94, Pages 12: Trend Analysis of Respiratory Disease Mortality in the Population Aged 65 and over in Poland: Results from a Registry Study (2000–2022)

Advances in Respiratory Medicine doi: 10.3390/arm94010012

Authors: Monika Burzyńska Małgorzata Pikala

Background: Respiratory diseases remain a major contributor to mortality in Europe, yet national long-term analyses rarely explore sex- and age-specific temporal patterns in detail. Large international datasets provide aggregated estimates but may obscure country-specific trend changes relevant for public health planning. The aim of the study was to assess long-term trends in mortality from chronic lower respiratory diseases (ICD-10: J40–J47) as well as pneumonia and influenza. (ICD-10: J10–J18) in Poland, with particular emphasis on sex- and age-specific trajectories and joinpoint-defined changes over time. Methods: All deaths among Polish residents aged ≥65 years were analysed using nationwide mortality registry data. Age-standardised death rates (SDRs) were calculated, and temporal trends were assessed using joinpoint regression models to estimate annual percentage changes (APC) and average annual percentage change (AAPC). Results: The proportion of deaths attributable to respiratory diseases increased in both men and women across early (65–74 years) and late (≥75 years) old age. Mortality from chronic lower respiratory diseases declined throughout the study period among men, with the most pronounced reductions observed in the early 2000s, particularly among those aged ≥75 years, while trends among women remained largely stable or showed only gradual declines. In contrast, mortality from pneumonia and influenza rose markedly across all sex and age subgroups, with distinct trend reversals observed after 2008–2009. Conclusions: Long-term respiratory mortality trends in Poland exhibit marked sex- and age-specific differences that are not fully captured by aggregated international analyses. These findings highlight the importance of country-level, stratified assessments when interpreting respiratory mortality patterns and underscore the need for caution when relying on single time-point indicators for risk assessment and policy planning.

]]> Trend Analysis of Respiratory Disease Mortality in the Population Aged 65 and over in Poland: Results from a Registry Study (2000–2022) Monika Burzyńska Małgorzata Pikala doi: 10.3390/arm94010012 Advances in Respiratory Medicine 2026-02-14 Advances in Respiratory Medicine 2026-02-14 94 1 Article 12 10.3390/arm94010012 https://www.mdpi.com/2543-6031/94/1/12 ARM, Vol. 94, Pages 11: The Role of L-Arginine and Liposomal Vitamin C Supplementation as an Adjunct in Seasonal Respiratory Viral Infection Recovery https://www.mdpi.com/2543-6031/94/1/11 Respiratory seasonal viral infections remain one of the most important issues in community medicine. The heterogeneity of etiological agents and the characteristics of the hosts airway antiviral defenses account for the complex management of these infections. The clinical consequence of this picture is that, despite the widespread use of vaccination as the primary prevention strategy, the rates of acute respiratory complications remain still high. In addition, they determine post-infectious fatigue and organ dysfunction. Inflammation and oxidative stress are the principal pathogenic mechanisms responsible for clinical complications during respiratory seasonal viral infections. Nowadays, a growing body of evidence indicates that adjunctive nutritional support can contribute to relieve the symptoms during the acute and subacute phases of respiratory viral infections. We assess the data in the literature regarding the combination of L-Arginine and Liposomal Vitamin C as adjuvant treatment for respiratory seasonal viral infections. The database of the National Library of Medicine (PubMed) was searched using the keywords “L-Arginine, Vitamin C, dietary supplements, seasonal respiratory viral infections”. The treatment of symptoms during acute and post-acute respiratory viral infections requires an integrated approach that includes vitamins and nutritional supplementation. The combination of L-Arginine and Liposomal Vitamin C seems to represent a nutritional support able to mitigate symptoms occurring during the acute or post-acute phase of infection. 2026-02-09 ARM, Vol. 94, Pages 11: The Role of L-Arginine and Liposomal Vitamin C Supplementation as an Adjunct in Seasonal Respiratory Viral Infection Recovery

Advances in Respiratory Medicine doi: 10.3390/arm94010011

Authors: Valentina Trimarco Paola Gallo Seyedali Ghazihosseini Alessia Izzo Paola Ida Rozza Alessandra Spinelli Stefano Cristiano Carlo De Rosa Felicia Rozza Carmine Morisco

Respiratory seasonal viral infections remain one of the most important issues in community medicine. The heterogeneity of etiological agents and the characteristics of the hosts airway antiviral defenses account for the complex management of these infections. The clinical consequence of this picture is that, despite the widespread use of vaccination as the primary prevention strategy, the rates of acute respiratory complications remain still high. In addition, they determine post-infectious fatigue and organ dysfunction. Inflammation and oxidative stress are the principal pathogenic mechanisms responsible for clinical complications during respiratory seasonal viral infections. Nowadays, a growing body of evidence indicates that adjunctive nutritional support can contribute to relieve the symptoms during the acute and subacute phases of respiratory viral infections. We assess the data in the literature regarding the combination of L-Arginine and Liposomal Vitamin C as adjuvant treatment for respiratory seasonal viral infections. The database of the National Library of Medicine (PubMed) was searched using the keywords “L-Arginine, Vitamin C, dietary supplements, seasonal respiratory viral infections”. The treatment of symptoms during acute and post-acute respiratory viral infections requires an integrated approach that includes vitamins and nutritional supplementation. The combination of L-Arginine and Liposomal Vitamin C seems to represent a nutritional support able to mitigate symptoms occurring during the acute or post-acute phase of infection.

]]> The Role of L-Arginine and Liposomal Vitamin C Supplementation as an Adjunct in Seasonal Respiratory Viral Infection Recovery Valentina Trimarco Paola Gallo Seyedali Ghazihosseini Alessia Izzo Paola Ida Rozza Alessandra Spinelli Stefano Cristiano Carlo De Rosa Felicia Rozza Carmine Morisco doi: 10.3390/arm94010011 Advances in Respiratory Medicine 2026-02-09 Advances in Respiratory Medicine 2026-02-09 94 1 Communication 11 10.3390/arm94010011 https://www.mdpi.com/2543-6031/94/1/11 ARM, Vol. 94, Pages 10: Differences in Causes, Severity, and Treatment Outcomes Between Women and Men with Chronic Cough https://www.mdpi.com/2543-6031/94/1/10 A chronic cough, defined as a cough persisting for more than eight weeks in adults, is a common clinical problem with a significant impact on patients’ quality of life. This study compares the etiological spectrum and treatment effectiveness of chronic cough in male and female patients. A retrospective analysis was conducted on a cohort of patients diagnosed in the cough clinic between 2017 and 2021. The response to treatment was assessed based on the reduction in cough severity measured using a 100 mm visual analogue scale (VAS). This study included 231 patients: 164 women (70.9%) and 67 men (29.1%). The median duration of cough was 48 months (IQR 24–120). There were no gender differences in age, BMI, smoking history, cough duration, or severity at the initial visit. Upper airway cough syndrome (UACS) and obstructive sleep apnea (OSA) were diagnosed more frequently in men than in women (UACS: 75% vs. 53%, p = 0.002; OSA: 21% vs. 6%, p = 0.001). Cough severity significantly decreased in both groups; the median VAS score dropped from 55 to 40 mm in women (p < 0.0001) and from 69 to 39 mm in men (p = 0.009). The effectiveness of chronic cough treatment, measured by the median reduction in VAS score, was greater in men than in women (32 mm vs. 17.5 mm, p = 0.006). These gender-specific differences in cough etiology and treatment response suggest that a “one-size-fits-all” approach may be inadequate. 2026-02-09 ARM, Vol. 94, Pages 10: Differences in Causes, Severity, and Treatment Outcomes Between Women and Men with Chronic Cough

Advances in Respiratory Medicine doi: 10.3390/arm94010010

Authors: Aleksandra Marchwińska Katarzyna Mazurek Katarzyna Białek-Gosk Elżbieta M. Grabczak Olga Truba Karolina Klimowicz Marta Dąbrowska

A chronic cough, defined as a cough persisting for more than eight weeks in adults, is a common clinical problem with a significant impact on patients’ quality of life. This study compares the etiological spectrum and treatment effectiveness of chronic cough in male and female patients. A retrospective analysis was conducted on a cohort of patients diagnosed in the cough clinic between 2017 and 2021. The response to treatment was assessed based on the reduction in cough severity measured using a 100 mm visual analogue scale (VAS). This study included 231 patients: 164 women (70.9%) and 67 men (29.1%). The median duration of cough was 48 months (IQR 24–120). There were no gender differences in age, BMI, smoking history, cough duration, or severity at the initial visit. Upper airway cough syndrome (UACS) and obstructive sleep apnea (OSA) were diagnosed more frequently in men than in women (UACS: 75% vs. 53%, p = 0.002; OSA: 21% vs. 6%, p = 0.001). Cough severity significantly decreased in both groups; the median VAS score dropped from 55 to 40 mm in women (p < 0.0001) and from 69 to 39 mm in men (p = 0.009). The effectiveness of chronic cough treatment, measured by the median reduction in VAS score, was greater in men than in women (32 mm vs. 17.5 mm, p = 0.006). These gender-specific differences in cough etiology and treatment response suggest that a “one-size-fits-all” approach may be inadequate.

]]> Differences in Causes, Severity, and Treatment Outcomes Between Women and Men with Chronic Cough Aleksandra Marchwińska Katarzyna Mazurek Katarzyna Białek-Gosk Elżbieta M. Grabczak Olga Truba Karolina Klimowicz Marta Dąbrowska doi: 10.3390/arm94010010 Advances in Respiratory Medicine 2026-02-09 Advances in Respiratory Medicine 2026-02-09 94 1 Article 10 10.3390/arm94010010 https://www.mdpi.com/2543-6031/94/1/10 ARM, Vol. 94, Pages 9: Neutralization of Microbiota-Derived Corisin Shows Early Amelioration of Advanced Pulmonary Fibrosis https://www.mdpi.com/2543-6031/94/1/9 Background: Corisin, a microbiota-derived proapoptotic peptide, has emerged as a key mediator of epithelial injury, inflammation, and acute exacerbation in fibrotic lung disease. Although acute corisin inhibition prevents exacerbations in experimental models, its therapeutic impact on established pulmonary fibrosis remains unclear. This study evaluated the short-term efficacy of corisin neutralization in advanced transforming growth factor-β1 (TGF-β1)-driven lung fibrosis. Methods: Male TGF-β1 transgenic mice with established fibrosis were allocated to computed tomography-matched groups and treated intraperitoneally with an anti-corisin monoclonal antibody (clone 21A) or control IgG every two days for one week. Bronchoalveolar lavage fluid (BALF) analysis, histopathology, assessment of apoptosis, Ashcroft scoring, and lung hydroxyproline quantification were performed on day 8. Results: Anti-corisin treatment significantly reduced BALF inflammatory cell counts, including macrophages and lymphocytes. Histological analyses demonstrated decreased alveolar epithelial apoptosis, reduced collagen deposition, and significantly lower Ashcroft fibrosis scores. Lung hydroxyproline content was also markedly decreased, indicating attenuation of extracellular matrix accumulation. Conclusions: Short-term neutralization of microbiota-derived corisin rapidly alleviates inflammation, epithelial injury, and fibrotic remodeling in advanced TGF-β1-induced pulmonary fibrosis. These findings identify corisin as an upstream driver of ongoing fibrogenesis and support its potential as a therapeutic target in progressive fibrotic lung disease. 2026-02-06 ARM, Vol. 94, Pages 9: Neutralization of Microbiota-Derived Corisin Shows Early Amelioration of Advanced Pulmonary Fibrosis

Advances in Respiratory Medicine doi: 10.3390/arm94010009

Authors: Kazuki Furuhashi Hajime Fujimoto Masaaki Toda Corina N. D’Alessandro-Gabazza Atsuro Takeshita Kota Nishihama Tomohito Okano Haruko Saiki Atsushi Tomaru Valeria Fridman D’Alessandro Isaac Cann Esteban C. Gabazza Taro Yasuma Osamu Hataji Tetsu Kobayashi

Background: Corisin, a microbiota-derived proapoptotic peptide, has emerged as a key mediator of epithelial injury, inflammation, and acute exacerbation in fibrotic lung disease. Although acute corisin inhibition prevents exacerbations in experimental models, its therapeutic impact on established pulmonary fibrosis remains unclear. This study evaluated the short-term efficacy of corisin neutralization in advanced transforming growth factor-β1 (TGF-β1)-driven lung fibrosis. Methods: Male TGF-β1 transgenic mice with established fibrosis were allocated to computed tomography-matched groups and treated intraperitoneally with an anti-corisin monoclonal antibody (clone 21A) or control IgG every two days for one week. Bronchoalveolar lavage fluid (BALF) analysis, histopathology, assessment of apoptosis, Ashcroft scoring, and lung hydroxyproline quantification were performed on day 8. Results: Anti-corisin treatment significantly reduced BALF inflammatory cell counts, including macrophages and lymphocytes. Histological analyses demonstrated decreased alveolar epithelial apoptosis, reduced collagen deposition, and significantly lower Ashcroft fibrosis scores. Lung hydroxyproline content was also markedly decreased, indicating attenuation of extracellular matrix accumulation. Conclusions: Short-term neutralization of microbiota-derived corisin rapidly alleviates inflammation, epithelial injury, and fibrotic remodeling in advanced TGF-β1-induced pulmonary fibrosis. These findings identify corisin as an upstream driver of ongoing fibrogenesis and support its potential as a therapeutic target in progressive fibrotic lung disease.

]]> Neutralization of Microbiota-Derived Corisin Shows Early Amelioration of Advanced Pulmonary Fibrosis Kazuki Furuhashi Hajime Fujimoto Masaaki Toda Corina N. D’Alessandro-Gabazza Atsuro Takeshita Kota Nishihama Tomohito Okano Haruko Saiki Atsushi Tomaru Valeria Fridman D’Alessandro Isaac Cann Esteban C. Gabazza Taro Yasuma Osamu Hataji Tetsu Kobayashi doi: 10.3390/arm94010009 Advances in Respiratory Medicine 2026-02-06 Advances in Respiratory Medicine 2026-02-06 94 1 Brief Report 9 10.3390/arm94010009 https://www.mdpi.com/2543-6031/94/1/9 ARM, Vol. 94, Pages 8: Continuous Positive Airway Pressure Versus Nocturnal Oxygen in Obstructive Sleep Apnea: A Propensity Score Matching Study https://www.mdpi.com/2543-6031/94/1/8 Background: Obstructive sleep apnea (OSA) affects quality of life and increases cardiovascular risk. Nocturnal oxygen therapy (NOT) offers a potential alternative for patients intolerant to CPAP. The objective of this study was to compare NOT and continuous positive airway pressure (CPAP) by evaluating five-year survival in patients with obstructive sleep apnea. Methods: A retrospective cohort study was conducted using propensity score matching (PSM) methodology. A PSM analysis was conducted to reduce selection bias due to differences in baseline characteristics between patients using CPAP and those receiving oxygen therapy. Balance between treated and untreated groups was assessed using standardized mean differences. A PSM was estimated using a logistic regression model, matching patients adherent to CPAP therapy to those treated with NOT. Results: A total of 497 patients with a confirmed diagnosis of OSA were included in the analysis. The mean age was 62.1 years (SD13.6), and 54.3% (270/497) were male. Overall, 42.1% (209/497) of the patients were over 65 years old. Of the total, 303 patients received CPAP therapy and 194 received NOT. After PSM, a matched cohort of 370 patients (185 per group) was obtained. The CPAP-treated group showed a significantly lower residual Apnea–Hypopnea Index compared to the oxygen therapy group (3.9, IQR: 1.8–6.5 vs. 15, IQR:7.5–29.1; p < 0.001), indicating better physiological control of respiratory events. Treatment with CPAP was associated with a significantly lower risk of mortality compared with NOT across analytical approaches, including weighted logistic regression (OR = 0.11; 95% CI 0.02–0.48; p = 0.004) and PSM with bootstrap estimation (ATT = −0.12; 95% CI −0.22 to −0.01; p = 0.030). Conclusions: In this cohort, higher five-year survival was observed among patients with OSA treated with CPAP compared with those receiving supplemental oxygen. These findings indicate a favorable association between CPAP use and long-term outcomes, supporting its role as the preferred first-line therapy in patients with OSA. 2026-01-26 ARM, Vol. 94, Pages 8: Continuous Positive Airway Pressure Versus Nocturnal Oxygen in Obstructive Sleep Apnea: A Propensity Score Matching Study

Advances in Respiratory Medicine doi: 10.3390/arm94010008

Authors: Carlos Granados-Burgos Eduardo Tuta-Quintero Paula Romero Laura Gómez-Castro Alirio Bastidas Johan Rincón Sergio Torres Diego Rodríguez Kamil Faizal Juan Moreno Santiago Monsalve Estefania Couto Sofia Yanes David Torres Juan Sandoval Juan Hernández

Background: Obstructive sleep apnea (OSA) affects quality of life and increases cardiovascular risk. Nocturnal oxygen therapy (NOT) offers a potential alternative for patients intolerant to CPAP. The objective of this study was to compare NOT and continuous positive airway pressure (CPAP) by evaluating five-year survival in patients with obstructive sleep apnea. Methods: A retrospective cohort study was conducted using propensity score matching (PSM) methodology. A PSM analysis was conducted to reduce selection bias due to differences in baseline characteristics between patients using CPAP and those receiving oxygen therapy. Balance between treated and untreated groups was assessed using standardized mean differences. A PSM was estimated using a logistic regression model, matching patients adherent to CPAP therapy to those treated with NOT. Results: A total of 497 patients with a confirmed diagnosis of OSA were included in the analysis. The mean age was 62.1 years (SD13.6), and 54.3% (270/497) were male. Overall, 42.1% (209/497) of the patients were over 65 years old. Of the total, 303 patients received CPAP therapy and 194 received NOT. After PSM, a matched cohort of 370 patients (185 per group) was obtained. The CPAP-treated group showed a significantly lower residual Apnea–Hypopnea Index compared to the oxygen therapy group (3.9, IQR: 1.8–6.5 vs. 15, IQR:7.5–29.1; p < 0.001), indicating better physiological control of respiratory events. Treatment with CPAP was associated with a significantly lower risk of mortality compared with NOT across analytical approaches, including weighted logistic regression (OR = 0.11; 95% CI 0.02–0.48; p = 0.004) and PSM with bootstrap estimation (ATT = −0.12; 95% CI −0.22 to −0.01; p = 0.030). Conclusions: In this cohort, higher five-year survival was observed among patients with OSA treated with CPAP compared with those receiving supplemental oxygen. These findings indicate a favorable association between CPAP use and long-term outcomes, supporting its role as the preferred first-line therapy in patients with OSA.

]]> Continuous Positive Airway Pressure Versus Nocturnal Oxygen in Obstructive Sleep Apnea: A Propensity Score Matching Study Carlos Granados-Burgos Eduardo Tuta-Quintero Paula Romero Laura Gómez-Castro Alirio Bastidas Johan Rincón Sergio Torres Diego Rodríguez Kamil Faizal Juan Moreno Santiago Monsalve Estefania Couto Sofia Yanes David Torres Juan Sandoval Juan Hernández doi: 10.3390/arm94010008 Advances in Respiratory Medicine 2026-01-26 Advances in Respiratory Medicine 2026-01-26 94 1 Article 8 10.3390/arm94010008 https://www.mdpi.com/2543-6031/94/1/8 ARM, Vol. 94, Pages 7: Rapid Inpatient Uptitration of Inhaled Treprostinil in PH-ILD Patients with Severe Phenotype https://www.mdpi.com/2543-6031/94/1/7 Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is a progressive condition with limited treatment options and associated with high mortality rates. Inhaled treprostinil (iTre) is the only approved therapy for PH-ILD and has been shown to improve exercise capacity and delay disease progression. However, the conventional outpatient titration schedule requires 8–16 weeks to achieve therapeutic dosing, which may delay clinical benefit in those with advanced disease. We conducted a retrospective study of six patients with severe PH-ILD admitted to a tertiary academic center for initiation of iTre using a rapid inpatient uptitration protocol. iTre was started at 3 breaths four times daily (QID) and increased by 2 additional breaths every 12–24 h as tolerated, aiming for ≥9–12 breaths QID within one week under close monitoring. All six patients achieved target dosing without dose reduction or interruption. At three-month follow-up, mean pulmonary artery pressure decreased from 42 ± 5.5 to 35.2 ± 4.5 mmHg, pulmonary vascular resistance from 8.0 ± 1.2 to 6.0 ± 0.9 WU, and cardiac index increased from 2.05 ± 0.13 to 2.15 ± 0.12 L/min/m2. No readmissions occurred within 90 days. This study demonstrates that rapid inpatient uptitration of iTre in severe PH-ILD is feasible and well-tolerated, with preliminary evidence of short-term hemodynamic improvement. 2026-01-09 ARM, Vol. 94, Pages 7: Rapid Inpatient Uptitration of Inhaled Treprostinil in PH-ILD Patients with Severe Phenotype

Advances in Respiratory Medicine doi: 10.3390/arm94010007

Authors: Chebly Dagher Allysse Thomas Suzie Al Absi Brett Carollo Garrett Fiscus Raj Parikh

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is a progressive condition with limited treatment options and associated with high mortality rates. Inhaled treprostinil (iTre) is the only approved therapy for PH-ILD and has been shown to improve exercise capacity and delay disease progression. However, the conventional outpatient titration schedule requires 8–16 weeks to achieve therapeutic dosing, which may delay clinical benefit in those with advanced disease. We conducted a retrospective study of six patients with severe PH-ILD admitted to a tertiary academic center for initiation of iTre using a rapid inpatient uptitration protocol. iTre was started at 3 breaths four times daily (QID) and increased by 2 additional breaths every 12–24 h as tolerated, aiming for ≥9–12 breaths QID within one week under close monitoring. All six patients achieved target dosing without dose reduction or interruption. At three-month follow-up, mean pulmonary artery pressure decreased from 42 ± 5.5 to 35.2 ± 4.5 mmHg, pulmonary vascular resistance from 8.0 ± 1.2 to 6.0 ± 0.9 WU, and cardiac index increased from 2.05 ± 0.13 to 2.15 ± 0.12 L/min/m2. No readmissions occurred within 90 days. This study demonstrates that rapid inpatient uptitration of iTre in severe PH-ILD is feasible and well-tolerated, with preliminary evidence of short-term hemodynamic improvement.

]]> Rapid Inpatient Uptitration of Inhaled Treprostinil in PH-ILD Patients with Severe Phenotype Chebly Dagher Allysse Thomas Suzie Al Absi Brett Carollo Garrett Fiscus Raj Parikh doi: 10.3390/arm94010007 Advances in Respiratory Medicine 2026-01-09 Advances in Respiratory Medicine 2026-01-09 94 1 Article 7 10.3390/arm94010007 https://www.mdpi.com/2543-6031/94/1/7 ARM, Vol. 94, Pages 6: Treatment Adherence and Persistence of Anti-Fibrotic Drugs in Real Life in Greece https://www.mdpi.com/2543-6031/94/1/6 Background: Nintedanib and pirfenidone are two anti-fibrotic agents for diseases within the interstitial lung diseases (ILDs) spectrum. Here, we provide a comprehensive analysis regarding treatment persistence and adherence rates for the Greek territory. Methods: This was a retrospective cohort study of patients initiating anti-fibrotic treatment during the period 2019–2023, utilizing data extracted from the National Electronic Prescription Database. Treatment persistence was defined as the duration from the date of the first prescription to the end of follow-up, death, or switching to another agent. Adherence was estimated based on the Medication Possession Ratio (MPR) metric. Results: Overall, 2112 patients were analyzed. The majority were naive, male patients with a diagnosis of idiopathic pulmonary fibrosis (IPF). The overall median treatment persistence was 40.2 months (95% CI: 35.5–44.6). Women and treatment-naive patients demonstrated longer median treatment persistence compared to their counterparts, while older patients demonstrated the lowest median persistence rates. Adherence levels remained high across the follow-up period (90%). Diagnosis of IPF and gastrointestinal comorbidities were associated with a higher risk of discontinuation. Conclusions: We have generated novel data concerning the factors that affect patients’ outcomes under anti-fibrotic therapy. These findings may provide helpful insights for the therapeutic management of ILDs. 2026-01-08 ARM, Vol. 94, Pages 6: Treatment Adherence and Persistence of Anti-Fibrotic Drugs in Real Life in Greece

Advances in Respiratory Medicine doi: 10.3390/arm94010006

Authors: Georgia Kourlaba Stylianos Ravanidis Garyfallia Stefanou Konstantinos Mathioudakis Anastasios Tsolakidis Dimitrios Zografopoulos

Background: Nintedanib and pirfenidone are two anti-fibrotic agents for diseases within the interstitial lung diseases (ILDs) spectrum. Here, we provide a comprehensive analysis regarding treatment persistence and adherence rates for the Greek territory. Methods: This was a retrospective cohort study of patients initiating anti-fibrotic treatment during the period 2019–2023, utilizing data extracted from the National Electronic Prescription Database. Treatment persistence was defined as the duration from the date of the first prescription to the end of follow-up, death, or switching to another agent. Adherence was estimated based on the Medication Possession Ratio (MPR) metric. Results: Overall, 2112 patients were analyzed. The majority were naive, male patients with a diagnosis of idiopathic pulmonary fibrosis (IPF). The overall median treatment persistence was 40.2 months (95% CI: 35.5–44.6). Women and treatment-naive patients demonstrated longer median treatment persistence compared to their counterparts, while older patients demonstrated the lowest median persistence rates. Adherence levels remained high across the follow-up period (90%). Diagnosis of IPF and gastrointestinal comorbidities were associated with a higher risk of discontinuation. Conclusions: We have generated novel data concerning the factors that affect patients’ outcomes under anti-fibrotic therapy. These findings may provide helpful insights for the therapeutic management of ILDs.

]]> Treatment Adherence and Persistence of Anti-Fibrotic Drugs in Real Life in Greece Georgia Kourlaba Stylianos Ravanidis Garyfallia Stefanou Konstantinos Mathioudakis Anastasios Tsolakidis Dimitrios Zografopoulos doi: 10.3390/arm94010006 Advances in Respiratory Medicine 2026-01-08 Advances in Respiratory Medicine 2026-01-08 94 1 Article 6 10.3390/arm94010006 https://www.mdpi.com/2543-6031/94/1/6 ARM, Vol. 94, Pages 5: Prediction of Chronic Obstructive Pulmonary Disease Using Machine Learning, Clinical Summary Notes, and Vital Signs: A Single-Center Retrospective Cohort Study in the United States https://www.mdpi.com/2543-6031/94/1/5 Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Early identification and timely intervention for COPD exacerbations can reduce hospitalizations and complications, as well as improve patient outcomes. Methods: To develop and evaluate predictive models for COPD exacerbations using machine learning (ML), we performed a retrospective study using intensive care unit patient records. Records including 31,667 clinical notes and 10,489 vital signs were used to train and validate two machine learning models to predict COPD exacerbations in patients with known or suspected COPD. Predictive performance was evaluated for support vector machine, quadratic discriminant analysis, and adaptive boosting algorithms using area under the receiver operating characteristic curve (AUC). Results: The clinical note-based support vector machine model achieved an AUC of 0.81 and accuracy of 84.0% in predicting COPD exacerbations. Data from patient monitors and hospital information systems provided sufficient information for accurate prediction, demonstrating the utility of combining physiological signals with clinical text data. Discussion: Clinically available patient data and vital signs can effectively predict COPD exacerbations, potentially enabling earlier interventions, improved outcomes, and reduced healthcare burden. These findings suggest that integrating unstructured clinical notes with structured vital signs using ML frameworks may improve early detection of exacerbation risk, thus enabling appropriate patient counseling, triage, and treatment based on COPD severity. 2026-01-07 ARM, Vol. 94, Pages 5: Prediction of Chronic Obstructive Pulmonary Disease Using Machine Learning, Clinical Summary Notes, and Vital Signs: A Single-Center Retrospective Cohort Study in the United States

Advances in Respiratory Medicine doi: 10.3390/arm94010005

Authors: Sabrina Meng Hersh Sagreiya Negar Orangi-Fard

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Early identification and timely intervention for COPD exacerbations can reduce hospitalizations and complications, as well as improve patient outcomes. Methods: To develop and evaluate predictive models for COPD exacerbations using machine learning (ML), we performed a retrospective study using intensive care unit patient records. Records including 31,667 clinical notes and 10,489 vital signs were used to train and validate two machine learning models to predict COPD exacerbations in patients with known or suspected COPD. Predictive performance was evaluated for support vector machine, quadratic discriminant analysis, and adaptive boosting algorithms using area under the receiver operating characteristic curve (AUC). Results: The clinical note-based support vector machine model achieved an AUC of 0.81 and accuracy of 84.0% in predicting COPD exacerbations. Data from patient monitors and hospital information systems provided sufficient information for accurate prediction, demonstrating the utility of combining physiological signals with clinical text data. Discussion: Clinically available patient data and vital signs can effectively predict COPD exacerbations, potentially enabling earlier interventions, improved outcomes, and reduced healthcare burden. These findings suggest that integrating unstructured clinical notes with structured vital signs using ML frameworks may improve early detection of exacerbation risk, thus enabling appropriate patient counseling, triage, and treatment based on COPD severity.

]]> Prediction of Chronic Obstructive Pulmonary Disease Using Machine Learning, Clinical Summary Notes, and Vital Signs: A Single-Center Retrospective Cohort Study in the United States Sabrina Meng Hersh Sagreiya Negar Orangi-Fard doi: 10.3390/arm94010005 Advances in Respiratory Medicine 2026-01-07 Advances in Respiratory Medicine 2026-01-07 94 1 Article 5 10.3390/arm94010005 https://www.mdpi.com/2543-6031/94/1/5 ARM, Vol. 94, Pages 4: Recommendations Following Hospitalization for Acute Exacerbation of COPD—A Consensus Statement of the Polish Respiratory Society https://www.mdpi.com/2543-6031/94/1/4 Introduction: This document presents recommendations of the Polish Respiratory Society on discharge instructions following hospitalization for an exacerbation of chronic obstructive pulmonary disease (COPD). Methods: The Delphi method was applied to achieve consensus among independent experts. Results: Fourteen recommendations were formulated. Experts emphasized that discharge summaries require clear graphical and editorial design to ensure readability for both patients and healthcare professionals. The involvement of a multidisciplinary team was recommended to provide coherent and comprehensive documentation. Discharge instructions should be discussed with the patient during hospitalization and supplemented with standardized educational materials provided separately. These materials should cover inhaler technique, smoking cessation, physical activity, pulmonary rehabilitation, and vaccination. For patients with respiratory failure, home oxygen therapy or non-invasive ventilation must be addressed. Discharge recommendations should highlight modifications in baseline COPD treatment and management of comorbidities. A personalized action plan for future exacerbations is essential, and dietary consultation is advised. Finally, discharge summaries should specify follow-up appointments and include prescriptions for inhaled medications. Conclusions: The Polish Respiratory Society recommends that discharge instructions be provided to all patients hospitalized for a COPD exacerbation. 2026-01-04 ARM, Vol. 94, Pages 4: Recommendations Following Hospitalization for Acute Exacerbation of COPD—A Consensus Statement of the Polish Respiratory Society

Advances in Respiratory Medicine doi: 10.3390/arm94010004

Authors: Adam Jerzy Białas Adam Barczyk Iwona Damps-Konstańska Aleksander Kania Krzysztof Kuziemski Justyna Ledwoch Krystyna Rasławska Małgorzata Czajkowska-Malinowska

Introduction: This document presents recommendations of the Polish Respiratory Society on discharge instructions following hospitalization for an exacerbation of chronic obstructive pulmonary disease (COPD). Methods: The Delphi method was applied to achieve consensus among independent experts. Results: Fourteen recommendations were formulated. Experts emphasized that discharge summaries require clear graphical and editorial design to ensure readability for both patients and healthcare professionals. The involvement of a multidisciplinary team was recommended to provide coherent and comprehensive documentation. Discharge instructions should be discussed with the patient during hospitalization and supplemented with standardized educational materials provided separately. These materials should cover inhaler technique, smoking cessation, physical activity, pulmonary rehabilitation, and vaccination. For patients with respiratory failure, home oxygen therapy or non-invasive ventilation must be addressed. Discharge recommendations should highlight modifications in baseline COPD treatment and management of comorbidities. A personalized action plan for future exacerbations is essential, and dietary consultation is advised. Finally, discharge summaries should specify follow-up appointments and include prescriptions for inhaled medications. Conclusions: The Polish Respiratory Society recommends that discharge instructions be provided to all patients hospitalized for a COPD exacerbation.

]]> Recommendations Following Hospitalization for Acute Exacerbation of COPD—A Consensus Statement of the Polish Respiratory Society Adam Jerzy Białas Adam Barczyk Iwona Damps-Konstańska Aleksander Kania Krzysztof Kuziemski Justyna Ledwoch Krystyna Rasławska Małgorzata Czajkowska-Malinowska doi: 10.3390/arm94010004 Advances in Respiratory Medicine 2026-01-04 Advances in Respiratory Medicine 2026-01-04 94 1 Guidelines 4 10.3390/arm94010004 https://www.mdpi.com/2543-6031/94/1/4 ARM, Vol. 94, Pages 3: Exploring the Risk: Investigating the Association Between Elderly-Onset Sarcoidosis (EOS) and Malignancy https://www.mdpi.com/2543-6031/94/1/3 Background: Elderly-onset sarcoidosis > 65 (EOS) is rare and occurs in patients over 65. Studies on its incidence, clinical features, and treatment are limited, and its link to malignancy remains complex. Objectives: In this study, we aimed to analyze the possible association between malignancy and the occurrence of sarcoidosis in elderly patients over 65 years old. Design: Monocentric, nested retrospective case–control study. Material and Methods: A retrospective study analyzed newly diagnosed sarcoidosis patients in the Loewenstein Lung Center, Baden-Württemberg, Germany, categorizing them into younger-onset (<65 years) and elderly-onset (≥65 years). Demographic data, smoking status, medical history, symptoms, diagnostic methods, and any prior malignancy history were collected. Results: A total of 447 patients were included (365 patients within the group of younger-onset sarcoidosis and 82 patients with EOS). The median age of the younger-onset group was 47 (47 [23–63] years), compared to 69 (69 [65–84] years), p ≤ 0.001. Female patients were more prevalent in the group of elderly-onsets (54.9%) compared to the younger-onset group (35.9%), corresponding to an odds ratio of 2.2 (95% CI: 1.3–3.5, p: 0.002). Regarding the past history of malignancy, patients who had a positive history of malignancy were more prevalent among the elderly-onset group (29.6%) compared to the younger-onset group (5%) [OR (95% CI): 8.1 (4.1–15.8), p ≤ 0.001]. In multivariable logistic regression analysis with malignancy as the outcome, increasing age at sarcoidosis diagnosis was independently associated with a higher likelihood of prior malignancy (adjusted OR 1.08 per year, 95% CI 1.04–1.12), whereas sex, smoking status, and cardiometabolic comorbidity (diabetes and/or hypertension) were not independently associated. Conclusions: Elderly-onset sarcoidosis (EOS) is a less frequent variant of sarcoidosis with limited data regarding the possible risk factors. The increased prevalence of malignancy observed among patients with elderly-onset sarcoidosis appeared to be largely driven by age rather than a distinct EOS-specific effect. Age-adjusted analyses are essential when interpreting malignancy risk in sarcoidosis, and future age-matched prospective studies are needed to clarify potential biological links and guide evidence-based screening strategies. 2026-01-02 ARM, Vol. 94, Pages 3: Exploring the Risk: Investigating the Association Between Elderly-Onset Sarcoidosis (EOS) and Malignancy

Advances in Respiratory Medicine doi: 10.3390/arm94010003

Authors: Ahmed Ehab Axel T. Kempa Ahmad Shalabi Noha Elkateb Nesrine Saad Farrag Heba Wagih Abdelwahab

Background: Elderly-onset sarcoidosis > 65 (EOS) is rare and occurs in patients over 65. Studies on its incidence, clinical features, and treatment are limited, and its link to malignancy remains complex. Objectives: In this study, we aimed to analyze the possible association between malignancy and the occurrence of sarcoidosis in elderly patients over 65 years old. Design: Monocentric, nested retrospective case–control study. Material and Methods: A retrospective study analyzed newly diagnosed sarcoidosis patients in the Loewenstein Lung Center, Baden-Württemberg, Germany, categorizing them into younger-onset (<65 years) and elderly-onset (≥65 years). Demographic data, smoking status, medical history, symptoms, diagnostic methods, and any prior malignancy history were collected. Results: A total of 447 patients were included (365 patients within the group of younger-onset sarcoidosis and 82 patients with EOS). The median age of the younger-onset group was 47 (47 [23–63] years), compared to 69 (69 [65–84] years), p ≤ 0.001. Female patients were more prevalent in the group of elderly-onsets (54.9%) compared to the younger-onset group (35.9%), corresponding to an odds ratio of 2.2 (95% CI: 1.3–3.5, p: 0.002). Regarding the past history of malignancy, patients who had a positive history of malignancy were more prevalent among the elderly-onset group (29.6%) compared to the younger-onset group (5%) [OR (95% CI): 8.1 (4.1–15.8), p ≤ 0.001]. In multivariable logistic regression analysis with malignancy as the outcome, increasing age at sarcoidosis diagnosis was independently associated with a higher likelihood of prior malignancy (adjusted OR 1.08 per year, 95% CI 1.04–1.12), whereas sex, smoking status, and cardiometabolic comorbidity (diabetes and/or hypertension) were not independently associated. Conclusions: Elderly-onset sarcoidosis (EOS) is a less frequent variant of sarcoidosis with limited data regarding the possible risk factors. The increased prevalence of malignancy observed among patients with elderly-onset sarcoidosis appeared to be largely driven by age rather than a distinct EOS-specific effect. Age-adjusted analyses are essential when interpreting malignancy risk in sarcoidosis, and future age-matched prospective studies are needed to clarify potential biological links and guide evidence-based screening strategies.

]]> Exploring the Risk: Investigating the Association Between Elderly-Onset Sarcoidosis (EOS) and Malignancy Ahmed Ehab Axel T. Kempa Ahmad Shalabi Noha Elkateb Nesrine Saad Farrag Heba Wagih Abdelwahab doi: 10.3390/arm94010003 Advances in Respiratory Medicine 2026-01-02 Advances in Respiratory Medicine 2026-01-02 94 1 Article 3 10.3390/arm94010003 https://www.mdpi.com/2543-6031/94/1/3 ARM, Vol. 94, Pages 2: Efficacy of Carbocisteine in Reducing Exacerbations in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials https://www.mdpi.com/2543-6031/94/1/2 This systematic review and meta-analysis aimed to evaluate the efficacy and safety of carbocisteine in reducing chronic obstructive pulmonary disease (COPD) exacerbations based on evidence from randomized controlled trials (RCTs). A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. RCTs comparing carbocisteine (1500 mg/day) with placebo in COPD patients, with a minimum follow-up of six months, were included. Data on exacerbation rates and adverse events were extracted and analyzed using a random-effects model. Four RCTs involving 1746 patients met inclusion criteria. Pooled analysis showed that carbocisteine significantly reduced the annual rate of acute exacerbations compared to placebo (WMD = −0.40; 95% CI: −0.69 to −0.11), with no significant increase in adverse events (OR = 1.02; 95% CI: 0.76 to 1.37). Mechanistically, carbocisteine improves mucociliary clearance, suppresses airway inflammation, reduces oxidative stress, and may hinder bacterial colonization. Carbocisteine is associated with a significant reduction in COPD exacerbations and demonstrates a favorable safety profile. It may serve as an effective adjunctive therapy in patients with frequent exacerbations and mucus hypersecretion. 2025-12-31 ARM, Vol. 94, Pages 2: Efficacy of Carbocisteine in Reducing Exacerbations in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Advances in Respiratory Medicine doi: 10.3390/arm94010002

Authors: Chia Kow Syed Hasan Kaeshaelya Thiruchelvam

This systematic review and meta-analysis aimed to evaluate the efficacy and safety of carbocisteine in reducing chronic obstructive pulmonary disease (COPD) exacerbations based on evidence from randomized controlled trials (RCTs). A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. RCTs comparing carbocisteine (1500 mg/day) with placebo in COPD patients, with a minimum follow-up of six months, were included. Data on exacerbation rates and adverse events were extracted and analyzed using a random-effects model. Four RCTs involving 1746 patients met inclusion criteria. Pooled analysis showed that carbocisteine significantly reduced the annual rate of acute exacerbations compared to placebo (WMD = −0.40; 95% CI: −0.69 to −0.11), with no significant increase in adverse events (OR = 1.02; 95% CI: 0.76 to 1.37). Mechanistically, carbocisteine improves mucociliary clearance, suppresses airway inflammation, reduces oxidative stress, and may hinder bacterial colonization. Carbocisteine is associated with a significant reduction in COPD exacerbations and demonstrates a favorable safety profile. It may serve as an effective adjunctive therapy in patients with frequent exacerbations and mucus hypersecretion.

]]> Efficacy of Carbocisteine in Reducing Exacerbations in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Chia Kow Syed Hasan Kaeshaelya Thiruchelvam doi: 10.3390/arm94010002 Advances in Respiratory Medicine 2025-12-31 Advances in Respiratory Medicine 2025-12-31 94 1 Communication 2 10.3390/arm94010002 https://www.mdpi.com/2543-6031/94/1/2 ARM, Vol. 94, Pages 1: Physical and Physiological Mechanisms of Emergent Hydrodynamic Pressure in High-Flow Nasal Cannula Therapy https://www.mdpi.com/2543-6031/94/1/1 High-flow nasal cannula (HFNC) therapy is frequently described as a positive pressure modality, yet this classification lacks mechanistic support. This critical narrative review integrates experimental, computational, and clinical evidence to examine the established physiological mechanisms underlying HFNC, with emphasis on precise terminology. The study clarifies that labeling HFNC as “positive pressure” is conceptually inaccurate, as the system delivers transient, flow-dependent pressures characteristic of open-circuit administration. Evidence is synthesized to quantify the relative contributions of nasopharyngeal dead-space clearance versus emergent pressure generation. Unlike CPAP, HFNC produces pressures ranging from 0.2 to 13.5 cmH2O, determined by airway geometry, leak magnitude, and mouth position. Fluid dynamic modeling using Bernoulli and Darcy–Weisbach equations demonstrates oscillatory rather than sustained pressures, with magnitudes linked to nasopharyngeal Reynolds numbers (2400–6000) and turbulent energy dissipation (30–60%). Clinical efficacy persists despite variable pressures, reflecting synergistic mechanisms: inspiratory flow matching (40–50% reduction in work of breathing), dead-space clearance (CO2 reduction, r = −0.77, p < 0.05), emergent pressure effects (10–20%), and thermal humidification (10–20%). Electrical impedance tomography reveals heterogeneous alveolar recruitment, with high-potential (54%) and low-potential (46%) phenotypes. Based on these mechanistic insights, this review proposes the term “emergent hydrodynamic pressure” to accurately describe HFNC’s transient, flow-dependent pressures. This terminology differentiates HFNC from conventional positive pressure systems and aligns language with the principles of fluid dynamics and respiratory physiology. 2025-12-26 ARM, Vol. 94, Pages 1: Physical and Physiological Mechanisms of Emergent Hydrodynamic Pressure in High-Flow Nasal Cannula Therapy

Advances in Respiratory Medicine doi: 10.3390/arm94010001

Authors: Jose Luis Estela-Zape

High-flow nasal cannula (HFNC) therapy is frequently described as a positive pressure modality, yet this classification lacks mechanistic support. This critical narrative review integrates experimental, computational, and clinical evidence to examine the established physiological mechanisms underlying HFNC, with emphasis on precise terminology. The study clarifies that labeling HFNC as “positive pressure” is conceptually inaccurate, as the system delivers transient, flow-dependent pressures characteristic of open-circuit administration. Evidence is synthesized to quantify the relative contributions of nasopharyngeal dead-space clearance versus emergent pressure generation. Unlike CPAP, HFNC produces pressures ranging from 0.2 to 13.5 cmH2O, determined by airway geometry, leak magnitude, and mouth position. Fluid dynamic modeling using Bernoulli and Darcy–Weisbach equations demonstrates oscillatory rather than sustained pressures, with magnitudes linked to nasopharyngeal Reynolds numbers (2400–6000) and turbulent energy dissipation (30–60%). Clinical efficacy persists despite variable pressures, reflecting synergistic mechanisms: inspiratory flow matching (40–50% reduction in work of breathing), dead-space clearance (CO2 reduction, r = −0.77, p < 0.05), emergent pressure effects (10–20%), and thermal humidification (10–20%). Electrical impedance tomography reveals heterogeneous alveolar recruitment, with high-potential (54%) and low-potential (46%) phenotypes. Based on these mechanistic insights, this review proposes the term “emergent hydrodynamic pressure” to accurately describe HFNC’s transient, flow-dependent pressures. This terminology differentiates HFNC from conventional positive pressure systems and aligns language with the principles of fluid dynamics and respiratory physiology.

]]> Physical and Physiological Mechanisms of Emergent Hydrodynamic Pressure in High-Flow Nasal Cannula Therapy Jose Luis Estela-Zape doi: 10.3390/arm94010001 Advances in Respiratory Medicine 2025-12-26 Advances in Respiratory Medicine 2025-12-26 94 1 Review 1 10.3390/arm94010001 https://www.mdpi.com/2543-6031/94/1/1 ARM, Vol. 93, Pages 58: Comparison of Typical and Atypical Community Acquired Pneumonia Cases in Hospitalized Patients in Two Tertiary Centers in Riyadh, Saudi Arabia https://www.mdpi.com/2543-6031/93/6/58 Background/Objectives: Community-acquired pneumonia (CAP) is classified into typical and atypical forms, with Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila being the most common atypical pathogens and Streptococcus pneumoniae and Haemophilus influenzae the most common typical organisms. This study aimed to compare the prevalence, demographics, and clinical outcomes of hospitalized typical and atypical CAP patients. Methods: A cross-sectional study was conducted from January 2016 to June 2022 at two tertiary hospitals in Riyadh, Saudi Arabia. All inpatients diagnosed with CAP by imaging and clinical findings were included, excluding viral cases. Outcomes measured included pathogen testing and identification, hospitalization duration, ICU stay, and in-hospital mortality. Results: Among 1238 CAP hospitalizations, 65% underwent molecular testing, with atypical pathogens detected in 17 cases (2.09%). Mycoplasma pneumoniae was the most common organism. The cases had an almost equal male-to-female ratio. Mean hospitalization was 12 days overall versus 4 days for atypical pneumonia. Of 265 ICU admissions, none tested positive for atypical CAP. Overall mortality was 6.94%, with no deaths in atypical pneumonia positive patients. Conclusions: PCR molecular testing was performed in 65% of patients hospitalized with CAP, and atypical pneumonia organisms were uncommon in these patients, with Mycoplasma pneumoniae being the most common. Clinical outcomes were more favorable for these patients. Expanding molecular testing may improve pathogen detection and guide target management. 2025-12-13 ARM, Vol. 93, Pages 58: Comparison of Typical and Atypical Community Acquired Pneumonia Cases in Hospitalized Patients in Two Tertiary Centers in Riyadh, Saudi Arabia

Advances in Respiratory Medicine doi: 10.3390/arm93060058

Authors: Abdullah Almufleh Abdulrahman Altuwayjiri Abdulmalik Alshehri Abdulaziz Alzouman Abdulhadi Alotaibi Abdulrahman Alsaedy

Background/Objectives: Community-acquired pneumonia (CAP) is classified into typical and atypical forms, with Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila being the most common atypical pathogens and Streptococcus pneumoniae and Haemophilus influenzae the most common typical organisms. This study aimed to compare the prevalence, demographics, and clinical outcomes of hospitalized typical and atypical CAP patients. Methods: A cross-sectional study was conducted from January 2016 to June 2022 at two tertiary hospitals in Riyadh, Saudi Arabia. All inpatients diagnosed with CAP by imaging and clinical findings were included, excluding viral cases. Outcomes measured included pathogen testing and identification, hospitalization duration, ICU stay, and in-hospital mortality. Results: Among 1238 CAP hospitalizations, 65% underwent molecular testing, with atypical pathogens detected in 17 cases (2.09%). Mycoplasma pneumoniae was the most common organism. The cases had an almost equal male-to-female ratio. Mean hospitalization was 12 days overall versus 4 days for atypical pneumonia. Of 265 ICU admissions, none tested positive for atypical CAP. Overall mortality was 6.94%, with no deaths in atypical pneumonia positive patients. Conclusions: PCR molecular testing was performed in 65% of patients hospitalized with CAP, and atypical pneumonia organisms were uncommon in these patients, with Mycoplasma pneumoniae being the most common. Clinical outcomes were more favorable for these patients. Expanding molecular testing may improve pathogen detection and guide target management.

]]> Comparison of Typical and Atypical Community Acquired Pneumonia Cases in Hospitalized Patients in Two Tertiary Centers in Riyadh, Saudi Arabia Abdullah Almufleh Abdulrahman Altuwayjiri Abdulmalik Alshehri Abdulaziz Alzouman Abdulhadi Alotaibi Abdulrahman Alsaedy doi: 10.3390/arm93060058 Advances in Respiratory Medicine 2025-12-13 Advances in Respiratory Medicine 2025-12-13 93 6 Article 58 10.3390/arm93060058 https://www.mdpi.com/2543-6031/93/6/58 ARM, Vol. 93, Pages 57: The Role of Preprocedural Computed Tomography Angiography in Enhancing Arterial Embolisation for Life-Threatening Haemoptysis: A Case Series https://www.mdpi.com/2543-6031/93/6/57 Haemoptysis arises from diverse respiratory diseases and may involve a broad spectrum of thoracic vessels. Arterial embolisation (AE) is an effective, repeatable, minimally invasive treatment option for life-threatening haemoptysis. This case series included 10 patients (mean age 34 years; six males; five with cystic fibrosis) who underwent 17 AE procedures for life-threatening haemoptysis between January 2018 and September 2025. The study assessed the role of wide-field computed tomography angiography (CTA), extending from the thoracic inlet to L2, in preprocedural planning, bleeding localisation and detection of systemic collaterals. CTA accurately predicted the culprit region in 16 out of 17 procedures. Non-bronchial systemic arteries were identified in 6 out of 10 patients, consistent with previous reports. CTA showed strong concordance with angiography and enabled the detection of uncommon collaterals, including subclavian and phrenic branches. Recurrence of hemoptysis occurred in one patient during follow-up; however, three patients were lost to follow-up. Wide-field CTA enhances the identification of systemic feeders and supports procedural planning, potentially reducing recurrence associated with missed culprit vessels. AE remains a valuable option for haemoptysis control in cystic fibrosis, with outcomes further improved following initiation of CFTR modulators. The small sample size and incomplete follow-up limit generalisability, but findings highlight the importance of CTA in guiding AE and improving clinical outcomes. 2025-12-11 ARM, Vol. 93, Pages 57: The Role of Preprocedural Computed Tomography Angiography in Enhancing Arterial Embolisation for Life-Threatening Haemoptysis: A Case Series

Advances in Respiratory Medicine doi: 10.3390/arm93060057

Authors: Anna Ziętarska Adam Dobek Piotr Białek Wojciech Szubert Sebastian Majewski Ludomir Stefańczyk

Haemoptysis arises from diverse respiratory diseases and may involve a broad spectrum of thoracic vessels. Arterial embolisation (AE) is an effective, repeatable, minimally invasive treatment option for life-threatening haemoptysis. This case series included 10 patients (mean age 34 years; six males; five with cystic fibrosis) who underwent 17 AE procedures for life-threatening haemoptysis between January 2018 and September 2025. The study assessed the role of wide-field computed tomography angiography (CTA), extending from the thoracic inlet to L2, in preprocedural planning, bleeding localisation and detection of systemic collaterals. CTA accurately predicted the culprit region in 16 out of 17 procedures. Non-bronchial systemic arteries were identified in 6 out of 10 patients, consistent with previous reports. CTA showed strong concordance with angiography and enabled the detection of uncommon collaterals, including subclavian and phrenic branches. Recurrence of hemoptysis occurred in one patient during follow-up; however, three patients were lost to follow-up. Wide-field CTA enhances the identification of systemic feeders and supports procedural planning, potentially reducing recurrence associated with missed culprit vessels. AE remains a valuable option for haemoptysis control in cystic fibrosis, with outcomes further improved following initiation of CFTR modulators. The small sample size and incomplete follow-up limit generalisability, but findings highlight the importance of CTA in guiding AE and improving clinical outcomes.

]]> The Role of Preprocedural Computed Tomography Angiography in Enhancing Arterial Embolisation for Life-Threatening Haemoptysis: A Case Series Anna Ziętarska Adam Dobek Piotr Białek Wojciech Szubert Sebastian Majewski Ludomir Stefańczyk doi: 10.3390/arm93060057 Advances in Respiratory Medicine 2025-12-11 Advances in Respiratory Medicine 2025-12-11 93 6 Article 57 10.3390/arm93060057 https://www.mdpi.com/2543-6031/93/6/57 ARM, Vol. 93, Pages 56: Breathing Interventions Improve Autonomic Function, Respiratory Efficiency and Stress in Dysfunctional Breathing: A Randomised Controlled Trial https://www.mdpi.com/2543-6031/93/6/56 Background: Dysfunctional breathing patterns may impair autonomic regulation and increase perceived stress. Breathing-based interventions, particularly those involving guided exercises and supportive tools, have the potential to provide non-pharmacological benefits. Methods: In this parallel two-arm randomized controlled trial, 14 women aged 35–45 years with signs of dysfunctional breathing and no comorbidities were recruited from a fitness club. Participants were randomly assigned (1:1) using a computer-generated sequence to an intervention group (n = 7) or a control group (n = 7). Blinding was not applied. Both groups completed a 6-week program of guided breathing exercises using the iBreathe app, while the intervention group additionally used mouth tape during sleep. The primary outcomes were heart rate variability (HRV) indices—root mean square of successive differences (RMSSD) and the high-frequency (HF) component. Secondary outcomes included respiratory rate, Hencho test performance, and perceived stress measured using the Perceived Stress Scale-10 (PSS-10) and a Visual Analogue Scale (VAS). All participants were included in the final analysis (no loss to follow-up). Results: The intervention group showed a significant increase in the HF component of HRV (p = 0.018) and improved Hencho test performance (p = 0.018). Both groups demonstrated significant reductions in respiratory rate (p < 0.05) and PSS scores (p < 0.05). Between-group differences were not significant for RMSSD or perceived stress. No adverse events were reported. Conclusions: A 6-week breathing intervention improved respiratory efficiency and reduced perceived stress among women with dysfunctional breathing. The additional of night-time mouth taping provided further benefits for HRV and respiratory control. Larger and longer trials are needed to confirm these findings. 2025-12-10 ARM, Vol. 93, Pages 56: Breathing Interventions Improve Autonomic Function, Respiratory Efficiency and Stress in Dysfunctional Breathing: A Randomised Controlled Trial

Advances in Respiratory Medicine doi: 10.3390/arm93060056

Authors: Laura Zaliene Alvina Mockute Lina Levickiene

Background: Dysfunctional breathing patterns may impair autonomic regulation and increase perceived stress. Breathing-based interventions, particularly those involving guided exercises and supportive tools, have the potential to provide non-pharmacological benefits. Methods: In this parallel two-arm randomized controlled trial, 14 women aged 35–45 years with signs of dysfunctional breathing and no comorbidities were recruited from a fitness club. Participants were randomly assigned (1:1) using a computer-generated sequence to an intervention group (n = 7) or a control group (n = 7). Blinding was not applied. Both groups completed a 6-week program of guided breathing exercises using the iBreathe app, while the intervention group additionally used mouth tape during sleep. The primary outcomes were heart rate variability (HRV) indices—root mean square of successive differences (RMSSD) and the high-frequency (HF) component. Secondary outcomes included respiratory rate, Hencho test performance, and perceived stress measured using the Perceived Stress Scale-10 (PSS-10) and a Visual Analogue Scale (VAS). All participants were included in the final analysis (no loss to follow-up). Results: The intervention group showed a significant increase in the HF component of HRV (p = 0.018) and improved Hencho test performance (p = 0.018). Both groups demonstrated significant reductions in respiratory rate (p < 0.05) and PSS scores (p < 0.05). Between-group differences were not significant for RMSSD or perceived stress. No adverse events were reported. Conclusions: A 6-week breathing intervention improved respiratory efficiency and reduced perceived stress among women with dysfunctional breathing. The additional of night-time mouth taping provided further benefits for HRV and respiratory control. Larger and longer trials are needed to confirm these findings.

]]> Breathing Interventions Improve Autonomic Function, Respiratory Efficiency and Stress in Dysfunctional Breathing: A Randomised Controlled Trial Laura Zaliene Alvina Mockute Lina Levickiene doi: 10.3390/arm93060056 Advances in Respiratory Medicine 2025-12-10 Advances in Respiratory Medicine 2025-12-10 93 6 Article 56 10.3390/arm93060056 https://www.mdpi.com/2543-6031/93/6/56 ARM, Vol. 93, Pages 55: Cryptic Circulation and Co-Infections of Endemic Human Coronaviruses During the First Years of the COVID-19 Pandemic in Brazil https://www.mdpi.com/2543-6031/93/6/55 During the COVID-19 pandemic, the global focus on SARS-CoV-2 overshadowed the epidemiology of other respiratory pathogens. This study aimed to characterize the circulation of endemic human coronaviruses (HCoVs) in Brazil. We retrospectively analyzed results from 22,472 PCR tests for HCoVs (from 5183 patients) and 601,278 tests for SARS-CoV-2 (from 475,856 patients) between November 2019 and June 2021. HCoVs were detected in 160 patients (3.09%), with HCoV-NL63 as the most frequent species. HCoV circulation was intermittent, with positivity peaks up to 4% but also periods of up to six months with an absence of detections in 2020, contrasting with the sustained high positivity of SARS-CoV-2 (22.37%). Co-infections were frequent: 26.25% of HCoV-positive patients were co-infected with at least one other respiratory pathogen, most commonly Rhinovirus/Enterovirus, and cases involving up to five pathogens were observed, seven patients had co-infections between HCoVs and SARS-CoV-2. These findings reveal the persistent, often cryptic, circulation of HCoVs during the pandemic and highlight their role as key components in complex multi-pathogen infections. This underscores the critical importance of implementing comprehensive molecular diagnostic panels in routine respiratory surveillance to ensure accurate etiology, guide appropriate clinical management, and fully assess the public health burden of non-SARS-CoV-2 coronaviruses. 2025-12-05 ARM, Vol. 93, Pages 55: Cryptic Circulation and Co-Infections of Endemic Human Coronaviruses During the First Years of the COVID-19 Pandemic in Brazil

Advances in Respiratory Medicine doi: 10.3390/arm93060055

Authors: Ana Karolina Mendes Moreno Rajiv Gandhi Gopalsamy Lucas Alves da Mota Santana Marina dos Santos Barreto Pedro Henrique Macedo Moura Deise Maria Rego Rodrigues Silva Túlio César Rodrigues Leite Camila de Paula Dias Breno de Melo Silva Lysandro Pinto Borges Ricardo Lemes Gonçalves

During the COVID-19 pandemic, the global focus on SARS-CoV-2 overshadowed the epidemiology of other respiratory pathogens. This study aimed to characterize the circulation of endemic human coronaviruses (HCoVs) in Brazil. We retrospectively analyzed results from 22,472 PCR tests for HCoVs (from 5183 patients) and 601,278 tests for SARS-CoV-2 (from 475,856 patients) between November 2019 and June 2021. HCoVs were detected in 160 patients (3.09%), with HCoV-NL63 as the most frequent species. HCoV circulation was intermittent, with positivity peaks up to 4% but also periods of up to six months with an absence of detections in 2020, contrasting with the sustained high positivity of SARS-CoV-2 (22.37%). Co-infections were frequent: 26.25% of HCoV-positive patients were co-infected with at least one other respiratory pathogen, most commonly Rhinovirus/Enterovirus, and cases involving up to five pathogens were observed, seven patients had co-infections between HCoVs and SARS-CoV-2. These findings reveal the persistent, often cryptic, circulation of HCoVs during the pandemic and highlight their role as key components in complex multi-pathogen infections. This underscores the critical importance of implementing comprehensive molecular diagnostic panels in routine respiratory surveillance to ensure accurate etiology, guide appropriate clinical management, and fully assess the public health burden of non-SARS-CoV-2 coronaviruses.

]]> Cryptic Circulation and Co-Infections of Endemic Human Coronaviruses During the First Years of the COVID-19 Pandemic in Brazil Ana Karolina Mendes Moreno Rajiv Gandhi Gopalsamy Lucas Alves da Mota Santana Marina dos Santos Barreto Pedro Henrique Macedo Moura Deise Maria Rego Rodrigues Silva Túlio César Rodrigues Leite Camila de Paula Dias Breno de Melo Silva Lysandro Pinto Borges Ricardo Lemes Gonçalves doi: 10.3390/arm93060055 Advances in Respiratory Medicine 2025-12-05 Advances in Respiratory Medicine 2025-12-05 93 6 Article 55 10.3390/arm93060055 https://www.mdpi.com/2543-6031/93/6/55 ARM, Vol. 93, Pages 54: Prevalence of Urinary Tract Cancer in Patients with Obstructive Sleep Apnea: Data from the Vercelli Registry https://www.mdpi.com/2543-6031/93/6/54 Background: Obstructive sleep apnea (OSA) is recognized as a systemic disorder associated with several comorbidities, including renal dysfunction, which may improve with continuous positive airway pressure (C-PAP) therapy. Sleep fragmentation and nocturnal hypoxia characteristic of OSA have been implicated in carcinogenesis, particularly affecting hypoxia-sensitive urinary tract tissues. This study aimed to assess the prevalence of different cancer types among patients with concurrent OSA and malignancy and to characterize the clinical profiles of those with urinary tract cancer. Methods: We retrospectively analyzed 50 patients with both OSA and cancer from the Vercelli Hospital Registry. Cancer diagnoses were collected at the time of OSA diagnosis, prior to C-PAP initiation. Results: Among the cohort (70% males) of OSA-cancer patients, urinary tract cancers were the most frequent (34%), followed by breast (14%), colorectal (12%), lung (10%), laryngeal and skin (8%), intracranial (6%), hematologic and parotid (4%), and other cancers (2%); 10% had multiple cancer sites. Patients with urinary tract cancer were mainly male (88%, p = 0.0043) and displayed better respiratory indices, frequent hypertension, and higher C-PAP adherence. Conclusions: These findings suggest a possible link between OSA-related hypoxia and carcinogenesis in urinary tract tissues and support increased clinical surveillance and further research to determine potential protective effects of C-PAP therapy. 2025-11-27 ARM, Vol. 93, Pages 54: Prevalence of Urinary Tract Cancer in Patients with Obstructive Sleep Apnea: Data from the Vercelli Registry

Advances in Respiratory Medicine doi: 10.3390/arm93060054

Authors: Beatrice Ragnoli Patrizia Pochetti Fausto Chiazza Carlotta Bertelegni Danila Azzolina Mario Malerba

Background: Obstructive sleep apnea (OSA) is recognized as a systemic disorder associated with several comorbidities, including renal dysfunction, which may improve with continuous positive airway pressure (C-PAP) therapy. Sleep fragmentation and nocturnal hypoxia characteristic of OSA have been implicated in carcinogenesis, particularly affecting hypoxia-sensitive urinary tract tissues. This study aimed to assess the prevalence of different cancer types among patients with concurrent OSA and malignancy and to characterize the clinical profiles of those with urinary tract cancer. Methods: We retrospectively analyzed 50 patients with both OSA and cancer from the Vercelli Hospital Registry. Cancer diagnoses were collected at the time of OSA diagnosis, prior to C-PAP initiation. Results: Among the cohort (70% males) of OSA-cancer patients, urinary tract cancers were the most frequent (34%), followed by breast (14%), colorectal (12%), lung (10%), laryngeal and skin (8%), intracranial (6%), hematologic and parotid (4%), and other cancers (2%); 10% had multiple cancer sites. Patients with urinary tract cancer were mainly male (88%, p = 0.0043) and displayed better respiratory indices, frequent hypertension, and higher C-PAP adherence. Conclusions: These findings suggest a possible link between OSA-related hypoxia and carcinogenesis in urinary tract tissues and support increased clinical surveillance and further research to determine potential protective effects of C-PAP therapy.

]]> Prevalence of Urinary Tract Cancer in Patients with Obstructive Sleep Apnea: Data from the Vercelli Registry Beatrice Ragnoli Patrizia Pochetti Fausto Chiazza Carlotta Bertelegni Danila Azzolina Mario Malerba doi: 10.3390/arm93060054 Advances in Respiratory Medicine 2025-11-27 Advances in Respiratory Medicine 2025-11-27 93 6 Article 54 10.3390/arm93060054 https://www.mdpi.com/2543-6031/93/6/54 ARM, Vol. 93, Pages 53: Effectiveness and Safety of Glycopyrronium–Formoterol–Budesonide Triple Therapy in Chronic Obstructive Pulmonary Disease (AIR-FORCE): An Open-Label Multi-Centric Phase 4 Study https://www.mdpi.com/2543-6031/93/6/53 Chronic obstructive pulmonary disease (COPD) is a major health burden in India with limited real-world data on triple inhaler therapy. This prospective, open-label, multi-center, single-arm, phase 4 study (October 2023–August 2024) assessed the effectiveness and safety of glycopyrronium/formoterol fumarate/budesonide (GFB) triple therapy, administered as metered-dose inhaler (MDI) or dry-powder inhaler (DPI), in Indian COPD patients. Symptomatic patients aged ≥40 years with minimum one exacerbation in the past year and receiving dual or monotherapy were included. GFB was delivered as MDI or DPI based on physician and patient preference. Primary outcomes were changes from baseline in trough forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and modified medical research council (mMRC) score over 24 weeks, with assessment of exacerbations, hospitalizations, rescue medication use, and safety. In 184 patients (70.65% male, mean age 53.7 years), GFB significantly improved FEV1, FVC, and mMRC scores. Eleven mild exacerbations were reported without hospitalization; 17.39% used rescue salbutamol largely in the first 4 weeks. GFB was well tolerated, with mild-to-moderate adverse events in 14.67%, and outcomes were comparable between MDI and DPI. Our findings support GFB as safe and effective treatment in real-world COPD management. 2025-11-25 ARM, Vol. 93, Pages 53: Effectiveness and Safety of Glycopyrronium–Formoterol–Budesonide Triple Therapy in Chronic Obstructive Pulmonary Disease (AIR-FORCE): An Open-Label Multi-Centric Phase 4 Study

Advances in Respiratory Medicine doi: 10.3390/arm93060053

Authors: Anjali R. Nath Adesh Kumar Amit Suresh Bhate Bharat Mehrotra Deependra Kumar Rai Vijay Kumar Barge Divya Bhojwani Sagar Bhagat Sumit Bhushan Saiprasad Patil Hanmant Barkate

Chronic obstructive pulmonary disease (COPD) is a major health burden in India with limited real-world data on triple inhaler therapy. This prospective, open-label, multi-center, single-arm, phase 4 study (October 2023–August 2024) assessed the effectiveness and safety of glycopyrronium/formoterol fumarate/budesonide (GFB) triple therapy, administered as metered-dose inhaler (MDI) or dry-powder inhaler (DPI), in Indian COPD patients. Symptomatic patients aged ≥40 years with minimum one exacerbation in the past year and receiving dual or monotherapy were included. GFB was delivered as MDI or DPI based on physician and patient preference. Primary outcomes were changes from baseline in trough forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and modified medical research council (mMRC) score over 24 weeks, with assessment of exacerbations, hospitalizations, rescue medication use, and safety. In 184 patients (70.65% male, mean age 53.7 years), GFB significantly improved FEV1, FVC, and mMRC scores. Eleven mild exacerbations were reported without hospitalization; 17.39% used rescue salbutamol largely in the first 4 weeks. GFB was well tolerated, with mild-to-moderate adverse events in 14.67%, and outcomes were comparable between MDI and DPI. Our findings support GFB as safe and effective treatment in real-world COPD management.

]]> Effectiveness and Safety of Glycopyrronium–Formoterol–Budesonide Triple Therapy in Chronic Obstructive Pulmonary Disease (AIR-FORCE): An Open-Label Multi-Centric Phase 4 Study Anjali R. Nath Adesh Kumar Amit Suresh Bhate Bharat Mehrotra Deependra Kumar Rai Vijay Kumar Barge Divya Bhojwani Sagar Bhagat Sumit Bhushan Saiprasad Patil Hanmant Barkate doi: 10.3390/arm93060053 Advances in Respiratory Medicine 2025-11-25 Advances in Respiratory Medicine 2025-11-25 93 6 Article 53 10.3390/arm93060053 https://www.mdpi.com/2543-6031/93/6/53 ARM, Vol. 93, Pages 52: Preoperative Six-Minute Walking Distance as a Predictor of Postoperative Complications in Patients Undergoing Lobectomy for Non-Small-Cell Lung Cancer https://www.mdpi.com/2543-6031/93/6/52 Introduction: Minimally invasive video-assisted thoracic surgery (VATS) for lung cancer has become a widely used approach. However, postoperative pulmonary complications (PCs) such as pneumonia, atelectasis, and lung fistula remain significant challenges, particularly in older adult patients with multiple comorbidities. The 6-minute walk test (6MWT) has been suggested as a predictor of postoperative outcomes in various surgical settings, but its relationship with postoperative complications following VATS lobectomy for lung cancer has not been thoroughly explored. The aim of this study was to determine if preoperative 6MWD predicted the occurrence of 30-day PCs among patients undergoing VATS lobectomy for non-small-cell lung cancer. Methods: This retrospective study examined 66 patients who underwent VATS lobectomy for lung cancer. Participants were categorized into two groups: those with postoperative pulmonary complications (n = 11) and those without (n = 55). The research period was from January to September 2022. The preoperative 6MWT distance, along with other clinical and demographic factors, was assessed to determine its predictive value for postoperative complications. Multivariate logistic regression analysis was performed to identify significant predictors. Results: The study found that preoperative 6MWT ≤ 450 m was a significant predictor of postoperative pulmonary complications (odds ratio: 5.674, 95% CI: 1.206–26.684, p = 0.028). Conclusions: The preoperative 6MWT distance is a useful predictor of postoperative pulmonary complications in patients undergoing VATS lobectomy for lung cancer. Patients with a 6MWT ≤ 450 m may be at higher risk for complications such as pneumonia, atelectasis, and lung fistula. Incorporating preoperative 6MWT as a risk stratification tool could help guide clinical decisions and rehabilitation efforts to improve postoperative outcomes in this patient population. 2025-11-24 ARM, Vol. 93, Pages 52: Preoperative Six-Minute Walking Distance as a Predictor of Postoperative Complications in Patients Undergoing Lobectomy for Non-Small-Cell Lung Cancer

Advances in Respiratory Medicine doi: 10.3390/arm93060052

Authors: Naoki Maki Takahiro Yanagihara Ashoka Indranatha Wijesinghe Kazuto Sugai Tomoyuki Kawamura Yusuke Saeki Shinsuke Kitazawa Naohiro Kobayashi Shinji Kikuchi Yukinobu Goto Harumi Sakamoto Keisuke Taniguchi Hideo Ichimura Yukio Sato

Introduction: Minimally invasive video-assisted thoracic surgery (VATS) for lung cancer has become a widely used approach. However, postoperative pulmonary complications (PCs) such as pneumonia, atelectasis, and lung fistula remain significant challenges, particularly in older adult patients with multiple comorbidities. The 6-minute walk test (6MWT) has been suggested as a predictor of postoperative outcomes in various surgical settings, but its relationship with postoperative complications following VATS lobectomy for lung cancer has not been thoroughly explored. The aim of this study was to determine if preoperative 6MWD predicted the occurrence of 30-day PCs among patients undergoing VATS lobectomy for non-small-cell lung cancer. Methods: This retrospective study examined 66 patients who underwent VATS lobectomy for lung cancer. Participants were categorized into two groups: those with postoperative pulmonary complications (n = 11) and those without (n = 55). The research period was from January to September 2022. The preoperative 6MWT distance, along with other clinical and demographic factors, was assessed to determine its predictive value for postoperative complications. Multivariate logistic regression analysis was performed to identify significant predictors. Results: The study found that preoperative 6MWT ≤ 450 m was a significant predictor of postoperative pulmonary complications (odds ratio: 5.674, 95% CI: 1.206–26.684, p = 0.028). Conclusions: The preoperative 6MWT distance is a useful predictor of postoperative pulmonary complications in patients undergoing VATS lobectomy for lung cancer. Patients with a 6MWT ≤ 450 m may be at higher risk for complications such as pneumonia, atelectasis, and lung fistula. Incorporating preoperative 6MWT as a risk stratification tool could help guide clinical decisions and rehabilitation efforts to improve postoperative outcomes in this patient population.

]]> Preoperative Six-Minute Walking Distance as a Predictor of Postoperative Complications in Patients Undergoing Lobectomy for Non-Small-Cell Lung Cancer Naoki Maki Takahiro Yanagihara Ashoka Indranatha Wijesinghe Kazuto Sugai Tomoyuki Kawamura Yusuke Saeki Shinsuke Kitazawa Naohiro Kobayashi Shinji Kikuchi Yukinobu Goto Harumi Sakamoto Keisuke Taniguchi Hideo Ichimura Yukio Sato doi: 10.3390/arm93060052 Advances in Respiratory Medicine 2025-11-24 Advances in Respiratory Medicine 2025-11-24 93 6 Article 52 10.3390/arm93060052 https://www.mdpi.com/2543-6031/93/6/52 ARM, Vol. 93, Pages 51: A Unified Map of Airway Interactions: Secretome and Mechanotransduction Loops from Development to Disease https://www.mdpi.com/2543-6031/93/6/51 Human airways maintain homeostasis through intricate cellular interactomes combining secretome-mediated signalling and mechanotransduction feedback loops. This review presents the first unified map of bidirectional mechanobiology–secretome interactions between airway epithelial cells (AECs), smooth muscle cells (ASMCs), and chondrocytes. We unify a novel three-component regulatory architecture: epithelium functioning as environmental activators, smooth muscle as mechanical actuators, and cartilage as calcium-dependent regulators. Critical mechanotransduction pathways, particularly YAP/TAZ signalling and TRPV4 channels, directly couple matrix stiffness to cytokine release, creating a closed-loop feedback system. During development, ASM-driven FGF-10 signalling and peristaltic contractions orchestrate cartilage formation and epithelial differentiation through mechanically guided morphogenesis. In disease states, these homeostatic circuits become pathologically dysregulated; asthma and COPD exhibit feed-forward stiffness traps where increased matrix rigidity triggers YAP/TAZ-mediated hypercontractility, perpetuating further remodelling. Aberrant mechanotransduction drives smooth muscle hyperplasia, cartilage degradation, and epithelial dysfunction through sustained inflammatory cascades. This system-level understanding of airway cellular networks provides mechanistic frameworks for targeted therapeutic interventions and tissue engineering strategies that incorporate essential mechanobiological signalling requirements. 2025-11-12 ARM, Vol. 93, Pages 51: A Unified Map of Airway Interactions: Secretome and Mechanotransduction Loops from Development to Disease

Advances in Respiratory Medicine doi: 10.3390/arm93060051

Authors: Crizaldy Tugade Jopeth Ramis

Human airways maintain homeostasis through intricate cellular interactomes combining secretome-mediated signalling and mechanotransduction feedback loops. This review presents the first unified map of bidirectional mechanobiology–secretome interactions between airway epithelial cells (AECs), smooth muscle cells (ASMCs), and chondrocytes. We unify a novel three-component regulatory architecture: epithelium functioning as environmental activators, smooth muscle as mechanical actuators, and cartilage as calcium-dependent regulators. Critical mechanotransduction pathways, particularly YAP/TAZ signalling and TRPV4 channels, directly couple matrix stiffness to cytokine release, creating a closed-loop feedback system. During development, ASM-driven FGF-10 signalling and peristaltic contractions orchestrate cartilage formation and epithelial differentiation through mechanically guided morphogenesis. In disease states, these homeostatic circuits become pathologically dysregulated; asthma and COPD exhibit feed-forward stiffness traps where increased matrix rigidity triggers YAP/TAZ-mediated hypercontractility, perpetuating further remodelling. Aberrant mechanotransduction drives smooth muscle hyperplasia, cartilage degradation, and epithelial dysfunction through sustained inflammatory cascades. This system-level understanding of airway cellular networks provides mechanistic frameworks for targeted therapeutic interventions and tissue engineering strategies that incorporate essential mechanobiological signalling requirements.

]]> A Unified Map of Airway Interactions: Secretome and Mechanotransduction Loops from Development to Disease Crizaldy Tugade Jopeth Ramis doi: 10.3390/arm93060051 Advances in Respiratory Medicine 2025-11-12 Advances in Respiratory Medicine 2025-11-12 93 6 Review 51 10.3390/arm93060051 https://www.mdpi.com/2543-6031/93/6/51 ARM, Vol. 93, Pages 50: Unraveling the Complexities of Hypersensitivity Pneumonitis with Autoimmune Features: A Retrospective Analysis https://www.mdpi.com/2543-6031/93/6/50 Background: Some hypersensitivity pneumonitis (HP) patients exhibit autoimmune features (HPAF). This study compared outcomes of HPAF and HP without autoimmune features, focusing on progressive pulmonary fibrosis (PPF) and response to immunosuppression. Methods: A retrospective cohort study included HP patients from a single center. HPAF was defined as HP overlapping with autoimmune disease or presenting autoimmune markers/symptoms not fulfilling connective tissue disease criteria. A control HP group without autoimmune features was randomly selected. Demographics, autoimmune profiles, and outcomes over two years were analyzed. Results: 103 patients were included (52 HPAF; 51 HP). In HPAF, the most common autoimmune diseases were rheumatoid arthritis (9.6%), while 57.7% had isolated autoimmune serology. Groups showed no baseline differences in demographics, exposures, smoking, or lung function. Fibrotic disease on high-resolution CT at diagnosis was less frequent in HPAF (71.2% vs. 88.2%; p = 0.031). At two-year follow-up, survival, transplantation, and PPF prevalence were similar. HPAF patients received immunosuppression less often (69.2% vs. 86.3%; p = 0.038). Among patients under immunosuppression, PPF was significantly lower in HPAF group (8.6% vs. 29.5%; p = 0.021). Conclusions: Within two years post-diagnosis, HPAF and HP had comparable overall outcomes. However, under immunosuppression, HPAF patients had significantly lower odds of developing PPF (adjusted OR 0.08; 95% CI 0.008–0.816; p = 0.033) compared to HP patients, suggesting a more favorable treatment response. 2025-11-07 ARM, Vol. 93, Pages 50: Unraveling the Complexities of Hypersensitivity Pneumonitis with Autoimmune Features: A Retrospective Analysis

Advances in Respiratory Medicine doi: 10.3390/arm93060050

Authors: Joana Lourenço Sofia Castro David Barros Coelho André Terras Alexandre Natália Melo Patrícia Caetano Mota Hélder Novais Bastos André Carvalho António Morais

Background: Some hypersensitivity pneumonitis (HP) patients exhibit autoimmune features (HPAF). This study compared outcomes of HPAF and HP without autoimmune features, focusing on progressive pulmonary fibrosis (PPF) and response to immunosuppression. Methods: A retrospective cohort study included HP patients from a single center. HPAF was defined as HP overlapping with autoimmune disease or presenting autoimmune markers/symptoms not fulfilling connective tissue disease criteria. A control HP group without autoimmune features was randomly selected. Demographics, autoimmune profiles, and outcomes over two years were analyzed. Results: 103 patients were included (52 HPAF; 51 HP). In HPAF, the most common autoimmune diseases were rheumatoid arthritis (9.6%), while 57.7% had isolated autoimmune serology. Groups showed no baseline differences in demographics, exposures, smoking, or lung function. Fibrotic disease on high-resolution CT at diagnosis was less frequent in HPAF (71.2% vs. 88.2%; p = 0.031). At two-year follow-up, survival, transplantation, and PPF prevalence were similar. HPAF patients received immunosuppression less often (69.2% vs. 86.3%; p = 0.038). Among patients under immunosuppression, PPF was significantly lower in HPAF group (8.6% vs. 29.5%; p = 0.021). Conclusions: Within two years post-diagnosis, HPAF and HP had comparable overall outcomes. However, under immunosuppression, HPAF patients had significantly lower odds of developing PPF (adjusted OR 0.08; 95% CI 0.008–0.816; p = 0.033) compared to HP patients, suggesting a more favorable treatment response.

]]> Unraveling the Complexities of Hypersensitivity Pneumonitis with Autoimmune Features: A Retrospective Analysis Joana Lourenço Sofia Castro David Barros Coelho André Terras Alexandre Natália Melo Patrícia Caetano Mota Hélder Novais Bastos André Carvalho António Morais doi: 10.3390/arm93060050 Advances in Respiratory Medicine 2025-11-07 Advances in Respiratory Medicine 2025-11-07 93 6 Article 50 10.3390/arm93060050 https://www.mdpi.com/2543-6031/93/6/50 ARM, Vol. 93, Pages 49: A Plant-Based Diet Alleviates Molecular Pulmonary Abnormalities in Hypertension https://www.mdpi.com/2543-6031/93/6/49 Background: Essential hypertension is associated with an increased risk of pulmonary hypertension (PH). PH is diagnosed more frequently in females. Little is known about the effects of a plant-based diet (PBD) in improving lung abnormalities in PH. Methods: We compared 28- and 40-week-old female normotensive Wistar Kyoto and spontaneously hypertensive rats (SHR), maintained from the age of 4 weeks on a control refined diet or a PBD, comprising 28% fruits, vegetables, nuts and legumes. A subset of control SHRs were switched to the PBD at 28 weeks of age. Lungs were taken for protein and histological analysis. Results: Relative to WKYs, SHRs consuming the control diet exhibited decreased lung endothelial nitric oxide synthase (eNOS). PBD consumption by SHRs prevented and reversed this phenotype. Expression of E-cadherin was also reduced in SHRs. This reduction was attenuated by PBD consumption treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the lung was increased in SHRs and attenuated by PBD. The expression of activated transforming growth factor (TGF)-β1 was also attenuated by a PBD. Conclusions: The PBD favorably mediated hypertension-induced pulmonary molecular abnormalities in lung endothelium, epithelial junction and pro-fibrotic signaling. Future studies should assess the effects of a PBD in improving PH and lung function. 2025-11-04 ARM, Vol. 93, Pages 49: A Plant-Based Diet Alleviates Molecular Pulmonary Abnormalities in Hypertension

Advances in Respiratory Medicine doi: 10.3390/arm93060049

Authors: Rami Salim Najjar Jaishree Jagirdar Andrew T. Gewirtz

Background: Essential hypertension is associated with an increased risk of pulmonary hypertension (PH). PH is diagnosed more frequently in females. Little is known about the effects of a plant-based diet (PBD) in improving lung abnormalities in PH. Methods: We compared 28- and 40-week-old female normotensive Wistar Kyoto and spontaneously hypertensive rats (SHR), maintained from the age of 4 weeks on a control refined diet or a PBD, comprising 28% fruits, vegetables, nuts and legumes. A subset of control SHRs were switched to the PBD at 28 weeks of age. Lungs were taken for protein and histological analysis. Results: Relative to WKYs, SHRs consuming the control diet exhibited decreased lung endothelial nitric oxide synthase (eNOS). PBD consumption by SHRs prevented and reversed this phenotype. Expression of E-cadherin was also reduced in SHRs. This reduction was attenuated by PBD consumption treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the lung was increased in SHRs and attenuated by PBD. The expression of activated transforming growth factor (TGF)-β1 was also attenuated by a PBD. Conclusions: The PBD favorably mediated hypertension-induced pulmonary molecular abnormalities in lung endothelium, epithelial junction and pro-fibrotic signaling. Future studies should assess the effects of a PBD in improving PH and lung function.

]]> A Plant-Based Diet Alleviates Molecular Pulmonary Abnormalities in Hypertension Rami Salim Najjar Jaishree Jagirdar Andrew T. Gewirtz doi: 10.3390/arm93060049 Advances in Respiratory Medicine 2025-11-04 Advances in Respiratory Medicine 2025-11-04 93 6 Article 49 10.3390/arm93060049 https://www.mdpi.com/2543-6031/93/6/49 ARM, Vol. 93, Pages 48: Pulmonary Veno-Occlusive Disease: A Comprehensive Review of Diagnostic Challenges, Therapeutic Limitations, and Evolving Management https://www.mdpi.com/2543-6031/93/6/48 Pulmonary veno-occlusive disease (PVOD) is a rare and under-recognized cause of pulmonary hypertension. It is characterized by fibrotic obstruction of small pulmonary veins and venules. Its clinical presentation closely mimics pulmonary arterial hypertension (PAH), leading to frequent misdiagnosis, delayed recognition, and potentially harmful exposure to PAH-specific vasodilator therapy. This review aims to synthesize our evolving understanding of PVOD, discussing its etiologies, role of genetic underpinnings, histopathologic features, pathophysiology, clinical presentation, and characteristic imaging findings. It then discusses management strategies emphasizing early recognition, supportive care, avoidance of inappropriate PAH therapies due to poor response, and timely referral for lung transplantation. Despite advances in identification and management, PVOD remains a fatal condition with a median survival of less than two years, underscoring the importance of early recognition and multidisciplinary care. 2025-10-31 ARM, Vol. 93, Pages 48: Pulmonary Veno-Occlusive Disease: A Comprehensive Review of Diagnostic Challenges, Therapeutic Limitations, and Evolving Management

Advances in Respiratory Medicine doi: 10.3390/arm93060048

Authors: Brian Foster Sikandar Khan Ana Suarez Gonzalez Samantha Gillenwater

Pulmonary veno-occlusive disease (PVOD) is a rare and under-recognized cause of pulmonary hypertension. It is characterized by fibrotic obstruction of small pulmonary veins and venules. Its clinical presentation closely mimics pulmonary arterial hypertension (PAH), leading to frequent misdiagnosis, delayed recognition, and potentially harmful exposure to PAH-specific vasodilator therapy. This review aims to synthesize our evolving understanding of PVOD, discussing its etiologies, role of genetic underpinnings, histopathologic features, pathophysiology, clinical presentation, and characteristic imaging findings. It then discusses management strategies emphasizing early recognition, supportive care, avoidance of inappropriate PAH therapies due to poor response, and timely referral for lung transplantation. Despite advances in identification and management, PVOD remains a fatal condition with a median survival of less than two years, underscoring the importance of early recognition and multidisciplinary care.

]]> Pulmonary Veno-Occlusive Disease: A Comprehensive Review of Diagnostic Challenges, Therapeutic Limitations, and Evolving Management Brian Foster Sikandar Khan Ana Suarez Gonzalez Samantha Gillenwater doi: 10.3390/arm93060048 Advances in Respiratory Medicine 2025-10-31 Advances in Respiratory Medicine 2025-10-31 93 6 Review 48 10.3390/arm93060048 https://www.mdpi.com/2543-6031/93/6/48 ARM, Vol. 93, Pages 47: Leveraging Artificial Intelligence for the Diagnosis of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: Opportunities, Challenges, and Future Perspectives https://www.mdpi.com/2543-6031/93/5/47 Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a life-threatening vascular complication of SSc, marked by high morbidity and mortality. Early diagnosis remains a major challenge due to nonspecific symptoms and the limitations of conventional tools such as echocardiography (ECHO), pulmonary function tests (PFTs), and serum biomarkers. This review evaluates the emerging role of artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), in improving the diagnostic landscape of SSc-PAH. A comprehensive literature search was conducted across PubMed, Scopus, IEEE Xplore, Embase and Google Scholar to identify studies involving AI applications in SSc, pulmonary arterial hypertension (PAH), and their intersection. Evidence indicates that AI models can assist interpretation across modalities, including heart sounds, ECGs, chest X-rays (CXRs), ECHOs, CT pulmonary angiography (CTPA), and omics-based biomarkers. While several models show encouraging diagnostic performance, their accuracy varies by dataset and modality, and most require external validation against right heart catheterization (RHC)-confirmed cohorts. Integrating multimodal data through AI frameworks may enhance early recognition and individualized risk stratification; however, these tools remain exploratory. Future work should emphasize harmonized hemodynamic definitions, transparent validation protocols, and SSc-specific datasets to ensure clinical applicability and reproducibility. 2025-10-17 ARM, Vol. 93, Pages 47: Leveraging Artificial Intelligence for the Diagnosis of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: Opportunities, Challenges, and Future Perspectives

Advances in Respiratory Medicine doi: 10.3390/arm93050047

Authors: Samiksha Jain Avneet Kaur Abdul Qadeer Victor Ghosh Shivani Thota Mallareddy Banala Jieun Lee Gayathri Yerrapragada Poonguzhali Elangovan Mohammed Naveed Shariff Thangeswaran Natarajan Jayarajasekaran Janarthanan Jayavinamika Jayapradhaban Kala Samuel Richard Saai Poornima Vommi Shiva Sankari Karuppiah Anjani Muthyala Vivek N. Iyer Scott A. Helgeson Dipankar Mitra Shivaram P. Arunachalam

Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a life-threatening vascular complication of SSc, marked by high morbidity and mortality. Early diagnosis remains a major challenge due to nonspecific symptoms and the limitations of conventional tools such as echocardiography (ECHO), pulmonary function tests (PFTs), and serum biomarkers. This review evaluates the emerging role of artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), in improving the diagnostic landscape of SSc-PAH. A comprehensive literature search was conducted across PubMed, Scopus, IEEE Xplore, Embase and Google Scholar to identify studies involving AI applications in SSc, pulmonary arterial hypertension (PAH), and their intersection. Evidence indicates that AI models can assist interpretation across modalities, including heart sounds, ECGs, chest X-rays (CXRs), ECHOs, CT pulmonary angiography (CTPA), and omics-based biomarkers. While several models show encouraging diagnostic performance, their accuracy varies by dataset and modality, and most require external validation against right heart catheterization (RHC)-confirmed cohorts. Integrating multimodal data through AI frameworks may enhance early recognition and individualized risk stratification; however, these tools remain exploratory. Future work should emphasize harmonized hemodynamic definitions, transparent validation protocols, and SSc-specific datasets to ensure clinical applicability and reproducibility.

]]> Leveraging Artificial Intelligence for the Diagnosis of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: Opportunities, Challenges, and Future Perspectives Samiksha Jain Avneet Kaur Abdul Qadeer Victor Ghosh Shivani Thota Mallareddy Banala Jieun Lee Gayathri Yerrapragada Poonguzhali Elangovan Mohammed Naveed Shariff Thangeswaran Natarajan Jayarajasekaran Janarthanan Jayavinamika Jayapradhaban Kala Samuel Richard Saai Poornima Vommi Shiva Sankari Karuppiah Anjani Muthyala Vivek N. Iyer Scott A. Helgeson Dipankar Mitra Shivaram P. Arunachalam doi: 10.3390/arm93050047 Advances in Respiratory Medicine 2025-10-17 Advances in Respiratory Medicine 2025-10-17 93 5 Review 47 10.3390/arm93050047 https://www.mdpi.com/2543-6031/93/5/47 ARM, Vol. 93, Pages 46: Beyond the Apnea–Hypopnea Index: Exploring Time-Dependent Hazard Ratios of Respiratory Events in Obstructive Sleep Apnea https://www.mdpi.com/2543-6031/93/5/46 Obstructive sleep apnea (OSA) is associated with increased risks of systemic comorbidities, leading to significant morbidity and mortality. This study investigates predictors of all-cause mortality, emphasizing the interplay of clinical symptoms, polysomnographic findings, and comorbidities. The aim of this study was to identify and compare respiratory predictors of all-cause mortality over 5, 10, and 15 years. A single-center study was conducted at a Sleep Medicine Department between 2005 and 2019, 4025 patients with suspected OSA who underwent polysomnography were admitted, 853 died during the study. We performed Cox regression analyses with dynamic hazard ratios to evaluated predictors of mortality. Prevalence of OSA was high—75.6% in the cohort: 929 patients with mild OSA (23.1%), 770 with moderate OSA (19.1%), and 1343 with severe OSA (33.4%). Survival rates were 89.7%, 81.9%, and 78.8% at 5, 10, and 15 years, respectively. Cardiovascular causes dominated mortality (33.3%), followed by cancer (26.5%). AHIREM was associated with higher mortality risk in 0–5, 0–10, 0–15 years of observation in contrast to AHINREM and AHITST. The hazard ratio analysis showed that mortality risk changed over time depending on sleep stage and event type: risk increased for AHIREM and AHITST, while it stayed the same or decreased for AHINREM and most central apneas. 2025-10-16 ARM, Vol. 93, Pages 46: Beyond the Apnea–Hypopnea Index: Exploring Time-Dependent Hazard Ratios of Respiratory Events in Obstructive Sleep Apnea

Advances in Respiratory Medicine doi: 10.3390/arm93050046

Authors: Wojciech Kuczyński Aleksandra Kudrycka Karol Pierzchała Izabela Grabska-Kobyłecka Michael Pencina Sebastian Sakowski Piotr Białasiewicz

Obstructive sleep apnea (OSA) is associated with increased risks of systemic comorbidities, leading to significant morbidity and mortality. This study investigates predictors of all-cause mortality, emphasizing the interplay of clinical symptoms, polysomnographic findings, and comorbidities. The aim of this study was to identify and compare respiratory predictors of all-cause mortality over 5, 10, and 15 years. A single-center study was conducted at a Sleep Medicine Department between 2005 and 2019, 4025 patients with suspected OSA who underwent polysomnography were admitted, 853 died during the study. We performed Cox regression analyses with dynamic hazard ratios to evaluated predictors of mortality. Prevalence of OSA was high—75.6% in the cohort: 929 patients with mild OSA (23.1%), 770 with moderate OSA (19.1%), and 1343 with severe OSA (33.4%). Survival rates were 89.7%, 81.9%, and 78.8% at 5, 10, and 15 years, respectively. Cardiovascular causes dominated mortality (33.3%), followed by cancer (26.5%). AHIREM was associated with higher mortality risk in 0–5, 0–10, 0–15 years of observation in contrast to AHINREM and AHITST. The hazard ratio analysis showed that mortality risk changed over time depending on sleep stage and event type: risk increased for AHIREM and AHITST, while it stayed the same or decreased for AHINREM and most central apneas.

]]> Beyond the Apnea–Hypopnea Index: Exploring Time-Dependent Hazard Ratios of Respiratory Events in Obstructive Sleep Apnea Wojciech Kuczyński Aleksandra Kudrycka Karol Pierzchała Izabela Grabska-Kobyłecka Michael Pencina Sebastian Sakowski Piotr Białasiewicz doi: 10.3390/arm93050046 Advances in Respiratory Medicine 2025-10-16 Advances in Respiratory Medicine 2025-10-16 93 5 Article 46 10.3390/arm93050046 https://www.mdpi.com/2543-6031/93/5/46 ARM, Vol. 93, Pages 45: Correction: Román-Ríos et al. RSPH4A-PCDx: An Index to Predict Lung Function Decline in Primary Ciliary Dyskinesia. Adv. Respir. Med. 2025, 93, 27 https://www.mdpi.com/2543-6031/93/5/45 Figure Legend [...] 2025-10-15 ARM, Vol. 93, Pages 45: Correction: Román-Ríos et al. RSPH4A-PCDx: An Index to Predict Lung Function Decline in Primary Ciliary Dyskinesia. Adv. Respir. Med. 2025, 93, 27

Advances in Respiratory Medicine doi: 10.3390/arm93050045

Authors: Gabriel Román-Ríos Gabriel Rosario-Ortiz Marcos J. Ramos-Benitez Ricardo A. Mosquera Wilfredo De Jesús-Rojas

Figure Legend [...]

]]> Correction: Román-Ríos et al. RSPH4A-PCDx: An Index to Predict Lung Function Decline in Primary Ciliary Dyskinesia. Adv. Respir. Med. 2025, 93, 27 Gabriel Román-Ríos Gabriel Rosario-Ortiz Marcos J. Ramos-Benitez Ricardo A. Mosquera Wilfredo De Jesús-Rojas doi: 10.3390/arm93050045 Advances in Respiratory Medicine 2025-10-15 Advances in Respiratory Medicine 2025-10-15 93 5 Correction 45 10.3390/arm93050045 https://www.mdpi.com/2543-6031/93/5/45 ARM, Vol. 93, Pages 44: Pressurized Metered-Dose Inhaler Versus Dry Powder Inhaler Adherence Among Individuals with Asthma and COPD https://www.mdpi.com/2543-6031/93/5/44 Background: The core management of most individuals with asthma and COPD is daily treatment with inhalers such as inhaled corticosteroids (ICS) and long-acting bronchodilators. The two main types of inhalers used are pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Different studies have shown low adherence to inhaler treatments among subjects with asthma and COPD. In this study, we explored the differences in adherence between pMDIs and DPIs of combined ICS and long-acting β2-agonist inhalers (ICS + LABA) in a large cohort, free from commercial biases. Methods: In this historical prospective study, we included all adult subjects with asthma and/or COPD who acquired at least one ICS + LABA inhaler between 2016 and 2019. We carried out propensity score matching and then compared the maximal number of pMDIs and DPIs purchased in any continuous 12 months during the study period. We also compared once-a-day DPIs with twice-a-day DPIs. Results: Of the 36,998 matched subjects, 5897 (15.9%) purchased pMDIs. The overall median [IQR] inhalers purchased for pMDIs and DPIs were 1 [1, 4] and 3 [1, 8], respectively; for subjects with asthma, 1 [1, 3] and 2 [1, 6]; for subjects with COPD, 1 [1, 3] and 3 [1, 10]; and for subjects with asthma–COPD overlap, 2 [1, 7] and 6 [2, 12]. For all the comparisons, p < 0.001. The once-a-day DPI group had a slight but significantly better adherence than the twice-a-day DPI group. Conclusions: For ICS + LABA therapy, the number of DPIs purchased was significantly greater than the number of pMDIs purchased, as well as the once-a-day DPI relative to the other DPIs. Overall, subjects with asthma and/or COPD had low adherence to all inhalers, with the highest adherence observed among subjects with asthma–COPD overlap. 2025-10-11 ARM, Vol. 93, Pages 44: Pressurized Metered-Dose Inhaler Versus Dry Powder Inhaler Adherence Among Individuals with Asthma and COPD

Advances in Respiratory Medicine doi: 10.3390/arm93050044

Authors: Dekel Shlomi Bernice Oberman Yehonatan Halevy Shiri Kushnir Hadas Meir Yael Reichenberg

Background: The core management of most individuals with asthma and COPD is daily treatment with inhalers such as inhaled corticosteroids (ICS) and long-acting bronchodilators. The two main types of inhalers used are pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Different studies have shown low adherence to inhaler treatments among subjects with asthma and COPD. In this study, we explored the differences in adherence between pMDIs and DPIs of combined ICS and long-acting β2-agonist inhalers (ICS + LABA) in a large cohort, free from commercial biases. Methods: In this historical prospective study, we included all adult subjects with asthma and/or COPD who acquired at least one ICS + LABA inhaler between 2016 and 2019. We carried out propensity score matching and then compared the maximal number of pMDIs and DPIs purchased in any continuous 12 months during the study period. We also compared once-a-day DPIs with twice-a-day DPIs. Results: Of the 36,998 matched subjects, 5897 (15.9%) purchased pMDIs. The overall median [IQR] inhalers purchased for pMDIs and DPIs were 1 [1, 4] and 3 [1, 8], respectively; for subjects with asthma, 1 [1, 3] and 2 [1, 6]; for subjects with COPD, 1 [1, 3] and 3 [1, 10]; and for subjects with asthma–COPD overlap, 2 [1, 7] and 6 [2, 12]. For all the comparisons, p < 0.001. The once-a-day DPI group had a slight but significantly better adherence than the twice-a-day DPI group. Conclusions: For ICS + LABA therapy, the number of DPIs purchased was significantly greater than the number of pMDIs purchased, as well as the once-a-day DPI relative to the other DPIs. Overall, subjects with asthma and/or COPD had low adherence to all inhalers, with the highest adherence observed among subjects with asthma–COPD overlap.

]]> Pressurized Metered-Dose Inhaler Versus Dry Powder Inhaler Adherence Among Individuals with Asthma and COPD Dekel Shlomi Bernice Oberman Yehonatan Halevy Shiri Kushnir Hadas Meir Yael Reichenberg doi: 10.3390/arm93050044 Advances in Respiratory Medicine 2025-10-11 Advances in Respiratory Medicine 2025-10-11 93 5 Article 44 10.3390/arm93050044 https://www.mdpi.com/2543-6031/93/5/44 ARM, Vol. 93, Pages 43: The Effort, Dyspnea, and Cooperation Scores in Mild and Moderate Post-COVID-19 Patients: Results of a Retrospective Study https://www.mdpi.com/2543-6031/93/5/43 COVID-19 signs and symptoms varied among patients, with the most common being fever, fatigue, sore throat, cough, anorexia, and shortness of breath. (1) Background: This study aimed to assess effort, dyspnea, and cooperation scores in patients with mild and moderate post-COVID-19 forms, both at baseline and after completing a structured physical recovery program. (2) Methods: Our study included 160 post-COVID-19 patients who had experienced mild or moderate disease. (3) Results: Effort and dyspnea scores were significantly lower (p < 0.01), while cooperation scores were significantly higher after the rehabilitation program. Both men and women demonstrated significant increases in cooperation scores after recovery. Additionally, both groups showed statistically significant reductions in effort and dyspnea scores (p < 0.001). Among patients aged under and over 60 years, effort and dyspnea scores decreased after rehabilitation, and cooperation scores increased significantly (p < 0.001). No statistically significant differences were observed between genders in any of the three scores. Similarly, no significant differences by age were found in cooperation or dyspnea scores. A significant negative correlation was observed between cooperation and effort scores: patients with higher cooperation scores tended to report lower effort scores, and vice versa (p < 0.001, R = −0.571). (4) Conclusions: The improved cooperation demonstrated by patients during the physical recovery program was significantly associated with reductions in perceived effort and dyspnea, indicating a positive impact on post-COVID-19 rehabilitation outcomes. 2025-10-07 ARM, Vol. 93, Pages 43: The Effort, Dyspnea, and Cooperation Scores in Mild and Moderate Post-COVID-19 Patients: Results of a Retrospective Study

Advances in Respiratory Medicine doi: 10.3390/arm93050043

Authors: Ovidiu Cristian Chiriac Corina Sporea Daniela Miricescu Ana Raluca Mitrea Ileana Adela Vacaroiu Raluca Grigore Adriana Sarah Nica

COVID-19 signs and symptoms varied among patients, with the most common being fever, fatigue, sore throat, cough, anorexia, and shortness of breath. (1) Background: This study aimed to assess effort, dyspnea, and cooperation scores in patients with mild and moderate post-COVID-19 forms, both at baseline and after completing a structured physical recovery program. (2) Methods: Our study included 160 post-COVID-19 patients who had experienced mild or moderate disease. (3) Results: Effort and dyspnea scores were significantly lower (p < 0.01), while cooperation scores were significantly higher after the rehabilitation program. Both men and women demonstrated significant increases in cooperation scores after recovery. Additionally, both groups showed statistically significant reductions in effort and dyspnea scores (p < 0.001). Among patients aged under and over 60 years, effort and dyspnea scores decreased after rehabilitation, and cooperation scores increased significantly (p < 0.001). No statistically significant differences were observed between genders in any of the three scores. Similarly, no significant differences by age were found in cooperation or dyspnea scores. A significant negative correlation was observed between cooperation and effort scores: patients with higher cooperation scores tended to report lower effort scores, and vice versa (p < 0.001, R = −0.571). (4) Conclusions: The improved cooperation demonstrated by patients during the physical recovery program was significantly associated with reductions in perceived effort and dyspnea, indicating a positive impact on post-COVID-19 rehabilitation outcomes.

]]> The Effort, Dyspnea, and Cooperation Scores in Mild and Moderate Post-COVID-19 Patients: Results of a Retrospective Study Ovidiu Cristian Chiriac Corina Sporea Daniela Miricescu Ana Raluca Mitrea Ileana Adela Vacaroiu Raluca Grigore Adriana Sarah Nica doi: 10.3390/arm93050043 Advances in Respiratory Medicine 2025-10-07 Advances in Respiratory Medicine 2025-10-07 93 5 Article 43 10.3390/arm93050043 https://www.mdpi.com/2543-6031/93/5/43 ARM, Vol. 93, Pages 42: Usefulness of Blood Biomarkers in Screening Patients with Obstructive Sleep Apnea: Could Albumin Indices and Uric Acid-to-HDL Ratio Be New OSAS Severity Indices? https://www.mdpi.com/2543-6031/93/5/42 Background and Objectives: Hematological parameters are increasingly being investigated as readily accessible biomarkers for the diagnosis of obstructive sleep apnea syndrome (OSAS). In our study, we aimed to investigate the relationship between OSAS and albumin indices and the uric acid-to-HDL ratio (UHR). Methods: The demographic and laboratory data and AHI (apnea–hypopnea index) values of 613 patients who underwent polysomnography were obtained retrospectively from their files. Blood parameters such as white blood cells (WBCs), red blood cell distribution width (RDW), red blood cells (RBCs), hemoglobin (Hb), hematocrit (Hct), platelets (PLTs), C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and high-density lipoproteins (HDLs) were obtained from the files. Laboratory indices such as the BUN-to-albumin ratio (BAR), neutrophil-to-albumin ratio (NAR), RDW-to-albumin ratio (RAR), CRP-to-albumin ratio (CAR), and UHR were calculated. OSAS was categorized as simple snoring (SS) (control) (AHI < 5), mild (5 ≤ AHI < 15), moderate (15 ≤ AHI < 30), and severe (AHI ≥ 30). The patients were also grouped as severe (AHI ≥ 30) and non-severe (5 > AHI < 30) OSAS and compared in terms of laboratory parameters and indices. Results: Of the 613 participants, 366 (59.7%) were men, and the average age of participants was 55.22 ± 11.13 years. The biomarkers such as RBCs, Hb, Htc, CRP, BUN, creatinine, uric acid, HDLs, CAR, RAR, BAR, and UHR showed significant differences between OSAS patients and controls. WBCs, basophils, RBCs, RDW, Htc, PLTs, HDLs, uric acid, RAR, NAR, and UHR indices were significantly different between the severe OSAS and non-severe OSAS groups (p < 0.05). BAR (OR = 1.151; CI = 1.056 − 1.256; p = 0.001) and UHR (OR = 2.257; 95% CI = 1.507 − 3.382; p < 0.001) were the most important indices predicting OSAS, while RAR (OR = 1.844; CI = 1.224 − 2.778; p = 0.003) and UHR (OR = 2.203; 95% CI = 1.496 − 3.243; p < 0.001) were the strongest indices associated with severe OSAS. Conclusion: In our study, RAR, BAR, and UHR indices were closely associated with the presence and severity of OSAS. These indices can be considered low-cost, readily available methods for predicting OSAS patients. 2025-10-07 ARM, Vol. 93, Pages 42: Usefulness of Blood Biomarkers in Screening Patients with Obstructive Sleep Apnea: Could Albumin Indices and Uric Acid-to-HDL Ratio Be New OSAS Severity Indices?

Advances in Respiratory Medicine doi: 10.3390/arm93050042

Authors: Mihrican Yeşildağ Taha Tahir Bekçi

Background and Objectives: Hematological parameters are increasingly being investigated as readily accessible biomarkers for the diagnosis of obstructive sleep apnea syndrome (OSAS). In our study, we aimed to investigate the relationship between OSAS and albumin indices and the uric acid-to-HDL ratio (UHR). Methods: The demographic and laboratory data and AHI (apnea–hypopnea index) values of 613 patients who underwent polysomnography were obtained retrospectively from their files. Blood parameters such as white blood cells (WBCs), red blood cell distribution width (RDW), red blood cells (RBCs), hemoglobin (Hb), hematocrit (Hct), platelets (PLTs), C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and high-density lipoproteins (HDLs) were obtained from the files. Laboratory indices such as the BUN-to-albumin ratio (BAR), neutrophil-to-albumin ratio (NAR), RDW-to-albumin ratio (RAR), CRP-to-albumin ratio (CAR), and UHR were calculated. OSAS was categorized as simple snoring (SS) (control) (AHI < 5), mild (5 ≤ AHI < 15), moderate (15 ≤ AHI < 30), and severe (AHI ≥ 30). The patients were also grouped as severe (AHI ≥ 30) and non-severe (5 > AHI < 30) OSAS and compared in terms of laboratory parameters and indices. Results: Of the 613 participants, 366 (59.7%) were men, and the average age of participants was 55.22 ± 11.13 years. The biomarkers such as RBCs, Hb, Htc, CRP, BUN, creatinine, uric acid, HDLs, CAR, RAR, BAR, and UHR showed significant differences between OSAS patients and controls. WBCs, basophils, RBCs, RDW, Htc, PLTs, HDLs, uric acid, RAR, NAR, and UHR indices were significantly different between the severe OSAS and non-severe OSAS groups (p < 0.05). BAR (OR = 1.151; CI = 1.056 − 1.256; p = 0.001) and UHR (OR = 2.257; 95% CI = 1.507 − 3.382; p < 0.001) were the most important indices predicting OSAS, while RAR (OR = 1.844; CI = 1.224 − 2.778; p = 0.003) and UHR (OR = 2.203; 95% CI = 1.496 − 3.243; p < 0.001) were the strongest indices associated with severe OSAS. Conclusion: In our study, RAR, BAR, and UHR indices were closely associated with the presence and severity of OSAS. These indices can be considered low-cost, readily available methods for predicting OSAS patients.

]]> Usefulness of Blood Biomarkers in Screening Patients with Obstructive Sleep Apnea: Could Albumin Indices and Uric Acid-to-HDL Ratio Be New OSAS Severity Indices? Mihrican Yeşildağ Taha Tahir Bekçi doi: 10.3390/arm93050042 Advances in Respiratory Medicine 2025-10-07 Advances in Respiratory Medicine 2025-10-07 93 5 Article 42 10.3390/arm93050042 https://www.mdpi.com/2543-6031/93/5/42 ARM, Vol. 93, Pages 41: Development of a Tool to Assess the Severity of Pulmonary Hypertension in Patients with Interstitial Lung Disease: A Guide to Assist Therapeutic Choices https://www.mdpi.com/2543-6031/93/5/41 Background: Pulmonary hypertension (PH) is a frequent complication in patients with interstitial lung disease (ILD); its occurrence results in significant morbidity and mortality. Currently approved treatment options for PH-ILD include inhaled prostacyclin therapy, although this approach may be insufficient in patients who have developed simultaneous right ventricular failure. Moreover, there is no available treatment algorithm regarding the optimal therapy and timing of lung transplant referral for PH-ILD patients based on disease severity. Design/Methods: In this study, we created such a tool to guide PH-specific therapy in PH-ILD patients, especially as further treatment strategies are developed. We developed a 4-point PH-ILD Severity score that integrated both subjective and objective information (WHO FC, CI, TAPSE, PVR) from retrospective analysis of 57 PH-ILD patients. Results: A score of 3 or greater in the PH-ILD Severity score yielded an AUC of 0.831 (p < 0.001) for the composite endpoint of clinical worsening (hospitalization due to a cardiopulmonary indication; decrease in 6 min walk distance by >15% at 2 consecutive visits; all-cause mortality; lung transplantation). Conclusions: Further confirmation and evolution of this PH-ILD Severity score will assist in the development of optimal treatment plans in ILD patients diagnosed with concomitant PH. 2025-10-06 ARM, Vol. 93, Pages 41: Development of a Tool to Assess the Severity of Pulmonary Hypertension in Patients with Interstitial Lung Disease: A Guide to Assist Therapeutic Choices

Advances in Respiratory Medicine doi: 10.3390/arm93050041

Authors: Garrett Fiscus Chebly Dagher David O’Sullivan Brett Carollo Kristen Swanson Harrison W. Farber Raj Parikh

Background: Pulmonary hypertension (PH) is a frequent complication in patients with interstitial lung disease (ILD); its occurrence results in significant morbidity and mortality. Currently approved treatment options for PH-ILD include inhaled prostacyclin therapy, although this approach may be insufficient in patients who have developed simultaneous right ventricular failure. Moreover, there is no available treatment algorithm regarding the optimal therapy and timing of lung transplant referral for PH-ILD patients based on disease severity. Design/Methods: In this study, we created such a tool to guide PH-specific therapy in PH-ILD patients, especially as further treatment strategies are developed. We developed a 4-point PH-ILD Severity score that integrated both subjective and objective information (WHO FC, CI, TAPSE, PVR) from retrospective analysis of 57 PH-ILD patients. Results: A score of 3 or greater in the PH-ILD Severity score yielded an AUC of 0.831 (p < 0.001) for the composite endpoint of clinical worsening (hospitalization due to a cardiopulmonary indication; decrease in 6 min walk distance by >15% at 2 consecutive visits; all-cause mortality; lung transplantation). Conclusions: Further confirmation and evolution of this PH-ILD Severity score will assist in the development of optimal treatment plans in ILD patients diagnosed with concomitant PH.

]]> Development of a Tool to Assess the Severity of Pulmonary Hypertension in Patients with Interstitial Lung Disease: A Guide to Assist Therapeutic Choices Garrett Fiscus Chebly Dagher David O’Sullivan Brett Carollo Kristen Swanson Harrison W. Farber Raj Parikh doi: 10.3390/arm93050041 Advances in Respiratory Medicine 2025-10-06 Advances in Respiratory Medicine 2025-10-06 93 5 Article 41 10.3390/arm93050041 https://www.mdpi.com/2543-6031/93/5/41 ARM, Vol. 93, Pages 40: Real-World Efficacy of Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium on Diaphragmatic Workload Assessed by Ultrasound and Lung Function in Patients with Uncontrolled Asthma https://www.mdpi.com/2543-6031/93/5/40 Background: Uncontrolled asthma remains a significant clinical challenge, often linked to impaired lung function and increased diaphragmatic workload. Recent studies have shown promising results using a triple inhaled therapy comprising beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G). This study assessed the real-world efficacy of BDP/FF/G on lung function and diaphragmatic workload in patients with uncontrolled asthma. Methods: A prospective observational study enrolled 21 adult patients diagnosed with uncontrolled asthma despite high-dose ICS/LABA therapy. Patients underwent lung function tests and right diaphragmatic ultrasound assessments at baseline and after three months of treatment with BDP/FF/G (172/5/9 mcg, administered as two inhalations every 12 h). Results: After three months, significant improvements were observed in FEV1 (from 57.75 ± 12.30% to 75.10 ± 18.94%, p < 0.001) and FEF25–75 (from 47.80 ± 19.23% to 75.10 ± 36.06%, p < 0.001). Additionally, during the same period, we recorded significant reductions in residual volume (from 130.10 ± 28.20% to 92.55 ± 21.18%, p < 0.001) and total airway resistance (Rtot) (from 164.60 ± 83.21% to 140.70 ± 83.25%, p < 0.05). The mean asthma control test (ACT) score increased by 5.6 points (p < 0.001), surpassing the established minimal clinically important difference (MCID) of 3 points and raising the cohort mean above the well-controlled threshold. The right diaphragmatic workload was significantly decreased, as shown by a reduction in thickening fraction (TF) (from 63.86 ± 17.67% to 40.29 ± 16.65%, p < 0.01). Correlation analysis indicated significant associations between diaphragmatic function and some lung function parameters (FEV1, FEF25–75, and Rtot). Conclusions: In this real-world pilot, triple BDP/FF/G was linked to improvements in airflow, hyperinflation, symptoms, and a reduction in diaphragmatic thickening fraction, indicating potential physiological benefit. Due to the small sample size, single-centre design, and 3-month follow-up, these results should be viewed as hypothesis-generating and need to be confirmed in larger, controlled, multicentre studies with longer follow-up. 2025-10-01 ARM, Vol. 93, Pages 40: Real-World Efficacy of Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium on Diaphragmatic Workload Assessed by Ultrasound and Lung Function in Patients with Uncontrolled Asthma

Advances in Respiratory Medicine doi: 10.3390/arm93050040

Authors: Antonio Maiorano Anna Ferrante Bannera Chiara Lupia Daniela Pastore Emanuela Chiarella Giovanna Lucia Piazzetta Angelantonio Maglio Alessandro Vatrella Girolamo Pelaia Corrado Pelaia

Background: Uncontrolled asthma remains a significant clinical challenge, often linked to impaired lung function and increased diaphragmatic workload. Recent studies have shown promising results using a triple inhaled therapy comprising beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G). This study assessed the real-world efficacy of BDP/FF/G on lung function and diaphragmatic workload in patients with uncontrolled asthma. Methods: A prospective observational study enrolled 21 adult patients diagnosed with uncontrolled asthma despite high-dose ICS/LABA therapy. Patients underwent lung function tests and right diaphragmatic ultrasound assessments at baseline and after three months of treatment with BDP/FF/G (172/5/9 mcg, administered as two inhalations every 12 h). Results: After three months, significant improvements were observed in FEV1 (from 57.75 ± 12.30% to 75.10 ± 18.94%, p < 0.001) and FEF25–75 (from 47.80 ± 19.23% to 75.10 ± 36.06%, p < 0.001). Additionally, during the same period, we recorded significant reductions in residual volume (from 130.10 ± 28.20% to 92.55 ± 21.18%, p < 0.001) and total airway resistance (Rtot) (from 164.60 ± 83.21% to 140.70 ± 83.25%, p < 0.05). The mean asthma control test (ACT) score increased by 5.6 points (p < 0.001), surpassing the established minimal clinically important difference (MCID) of 3 points and raising the cohort mean above the well-controlled threshold. The right diaphragmatic workload was significantly decreased, as shown by a reduction in thickening fraction (TF) (from 63.86 ± 17.67% to 40.29 ± 16.65%, p < 0.01). Correlation analysis indicated significant associations between diaphragmatic function and some lung function parameters (FEV1, FEF25–75, and Rtot). Conclusions: In this real-world pilot, triple BDP/FF/G was linked to improvements in airflow, hyperinflation, symptoms, and a reduction in diaphragmatic thickening fraction, indicating potential physiological benefit. Due to the small sample size, single-centre design, and 3-month follow-up, these results should be viewed as hypothesis-generating and need to be confirmed in larger, controlled, multicentre studies with longer follow-up.

]]> Real-World Efficacy of Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium on Diaphragmatic Workload Assessed by Ultrasound and Lung Function in Patients with Uncontrolled Asthma Antonio Maiorano Anna Ferrante Bannera Chiara Lupia Daniela Pastore Emanuela Chiarella Giovanna Lucia Piazzetta Angelantonio Maglio Alessandro Vatrella Girolamo Pelaia Corrado Pelaia doi: 10.3390/arm93050040 Advances in Respiratory Medicine 2025-10-01 Advances in Respiratory Medicine 2025-10-01 93 5 Article 40 10.3390/arm93050040 https://www.mdpi.com/2543-6031/93/5/40 ARM, Vol. 93, Pages 39: NSCLC EGFR Mutation Prediction via Random Forest Model: A Clinical–CT–Radiomics Integration Approach https://www.mdpi.com/2543-6031/93/5/39 Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Accurate determination of epidermal growth factor receptor (EGFR) mutation status is essential for selecting patients eligible for tyrosine kinase inhibitors (TKIs). However, invasive genotyping is often limited by tissue accessibility and sample quality. This study presents a non-invasive machine learning model combining clinical data, CT morphological features, and radiomic descriptors to predict EGFR mutation status. A retrospective cohort of 138 patients with confirmed EGFR status and pre-treatment CT scans was analyzed. Radiomic features were extracted with PyRadiomics, and feature selection applied mutual information, Spearman correlation, and wrapper-based methods. Five Random Forest models were trained with different feature sets. The best-performing model, based on 11 selected variables, achieved an AUC of 0.91 (95% CI: 0.81–1.00) under stratified five-fold cross-validation, with an accuracy of 0.88 ± 0.03. Subgroup analysis showed that EGFR-WT had a performance of precision 0.93 ± 0.04, recall 0.92 ± 0.03, F1-score 0.91 ± 0.02, and EGFR-Mutant had a performance of precision 0.76 ± 0.05, recall 0.71 ± 0.05, F1-score 0.68 ± 0.04. SHapley Additive exPlanations (SHAP) analysis identified tobacco use, enhancement pattern, and gray-level-zone entropy as key predictors. Decision curve analysis confirmed clinical utility, supporting its role as a non-invasive tool for EGFR-screening. 2025-09-26 ARM, Vol. 93, Pages 39: NSCLC EGFR Mutation Prediction via Random Forest Model: A Clinical–CT–Radiomics Integration Approach

Advances in Respiratory Medicine doi: 10.3390/arm93050039

Authors: Anass Benfares Badreddine Alami Sara Boukansa Mamoun Qjidaa Ikram Benomar Mounia Serraj Ahmed Lakhssassi Mohammed Ouazzani Jamil Mustapha Maaroufi Hassan Qjidaa

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Accurate determination of epidermal growth factor receptor (EGFR) mutation status is essential for selecting patients eligible for tyrosine kinase inhibitors (TKIs). However, invasive genotyping is often limited by tissue accessibility and sample quality. This study presents a non-invasive machine learning model combining clinical data, CT morphological features, and radiomic descriptors to predict EGFR mutation status. A retrospective cohort of 138 patients with confirmed EGFR status and pre-treatment CT scans was analyzed. Radiomic features were extracted with PyRadiomics, and feature selection applied mutual information, Spearman correlation, and wrapper-based methods. Five Random Forest models were trained with different feature sets. The best-performing model, based on 11 selected variables, achieved an AUC of 0.91 (95% CI: 0.81–1.00) under stratified five-fold cross-validation, with an accuracy of 0.88 ± 0.03. Subgroup analysis showed that EGFR-WT had a performance of precision 0.93 ± 0.04, recall 0.92 ± 0.03, F1-score 0.91 ± 0.02, and EGFR-Mutant had a performance of precision 0.76 ± 0.05, recall 0.71 ± 0.05, F1-score 0.68 ± 0.04. SHapley Additive exPlanations (SHAP) analysis identified tobacco use, enhancement pattern, and gray-level-zone entropy as key predictors. Decision curve analysis confirmed clinical utility, supporting its role as a non-invasive tool for EGFR-screening.

]]> NSCLC EGFR Mutation Prediction via Random Forest Model: A Clinical–CT–Radiomics Integration Approach Anass Benfares Badreddine Alami Sara Boukansa Mamoun Qjidaa Ikram Benomar Mounia Serraj Ahmed Lakhssassi Mohammed Ouazzani Jamil Mustapha Maaroufi Hassan Qjidaa doi: 10.3390/arm93050039 Advances in Respiratory Medicine 2025-09-26 Advances in Respiratory Medicine 2025-09-26 93 5 Article 39 10.3390/arm93050039 https://www.mdpi.com/2543-6031/93/5/39 ARM, Vol. 93, Pages 38: Safety and Tolerability of Inhaled Aztreonam in Children and Adolescents: A Systematic Review and Meta-Analysis https://www.mdpi.com/2543-6031/93/5/38 Respiratory infections and chronic lung disease are major contributors to morbidity in children. Aztreonam lysine for inhalation (AZLI) delivers high local antibiotic concentrations while limiting systemic exposure; however, its safety in younger patients remains uncertain. This systematic review and meta-analysis searched MEDLINE, CENTRAL, and Google Scholar for randomized and observational studies reporting adverse events in children and adolescents (≤18 years) receiving AZLI, with no date limit. Fourteen studies were included. Most studies were moderate-to-high quality. Comparative analysis showed no clinically relevant increase in common adverse events relative to placebo or other inhaled antibiotics. The pooled relative risk for severe respiratory disorders (grade 3/4) was 1.65 (95% CI 1.07–2.57), suggesting a higher incidence of serious respiratory events, while a protective effect against decline in pulmonary function was observed (RR 0.70, 95% CI 0.54–0.90). Adverse events were generally mild; serious adverse events and hospitalizations were infrequent and comparable between groups. Cumulative prevalence estimates indicated that respiratory irritation occurred in 10–25% of patients, whereas systemic effects were uncommon. Overall, AZLI appears to have an acceptable tolerability and safety profile in children and adolescents, though careful monitoring is warranted, especially for severe respiratory events. 2025-09-26 ARM, Vol. 93, Pages 38: Safety and Tolerability of Inhaled Aztreonam in Children and Adolescents: A Systematic Review and Meta-Analysis

Advances in Respiratory Medicine doi: 10.3390/arm93050038

Authors: Valmir N. Rastely-Junior Hosanea S. N. Rocha Mitermayer G. Reis

Respiratory infections and chronic lung disease are major contributors to morbidity in children. Aztreonam lysine for inhalation (AZLI) delivers high local antibiotic concentrations while limiting systemic exposure; however, its safety in younger patients remains uncertain. This systematic review and meta-analysis searched MEDLINE, CENTRAL, and Google Scholar for randomized and observational studies reporting adverse events in children and adolescents (≤18 years) receiving AZLI, with no date limit. Fourteen studies were included. Most studies were moderate-to-high quality. Comparative analysis showed no clinically relevant increase in common adverse events relative to placebo or other inhaled antibiotics. The pooled relative risk for severe respiratory disorders (grade 3/4) was 1.65 (95% CI 1.07–2.57), suggesting a higher incidence of serious respiratory events, while a protective effect against decline in pulmonary function was observed (RR 0.70, 95% CI 0.54–0.90). Adverse events were generally mild; serious adverse events and hospitalizations were infrequent and comparable between groups. Cumulative prevalence estimates indicated that respiratory irritation occurred in 10–25% of patients, whereas systemic effects were uncommon. Overall, AZLI appears to have an acceptable tolerability and safety profile in children and adolescents, though careful monitoring is warranted, especially for severe respiratory events.

]]> Safety and Tolerability of Inhaled Aztreonam in Children and Adolescents: A Systematic Review and Meta-Analysis Valmir N. Rastely-Junior Hosanea S. N. Rocha Mitermayer G. Reis doi: 10.3390/arm93050038 Advances in Respiratory Medicine 2025-09-26 Advances in Respiratory Medicine 2025-09-26 93 5 Review 38 10.3390/arm93050038 https://www.mdpi.com/2543-6031/93/5/38 ARM, Vol. 93, Pages 37: FeNO 350 mL/s: Unlocking the Small Airways to Achieve Clinical Remission in Severe Asthma—A Pilot Study https://www.mdpi.com/2543-6031/93/5/37 Background: Several studies focused on the importance of managing small airways disease in the treatment of severe asthma, whose improvement can improve respiratory symptoms, lung function, and airways inflammation, potentially reaching the objective of clinical remission. Methods: Twenty-five patients with severe asthma and without bronchiectasis were enrolled. They were started on biological therapies with Omalizumab, Dupilumab, Benralizumab or Mepolizumab. Follow-up evaluations were conducted at baseline (T0) and after one year of biological therapy (T1). Assessments included clinical evaluations, spirometry, questionnaires, and inflammatory markers. Results: Predictive analysis identified baseline FeNO 350 mL/s levels as a significant predictor of clinical remission in both univariable and multivariable analysis. Higher FeNO 350 mL/s levels at T0 were associated with an increased likelihood of achieving remission (p = 0.012). The optimal cutoff value for FeNO 350 mL/s was determined to be 18 ppb, based on the Younden Index. Conclusions: Following patients with severe asthma on biological therapy for one year, FeNO 350 mL/s could be used as a predictive factor of clinical remission, highlighting its importance as inflammatory marker not only in small airways disease, but also in predicting clinical remission in severe asthmatic patients. 2025-09-17 ARM, Vol. 93, Pages 37: FeNO 350 mL/s: Unlocking the Small Airways to Achieve Clinical Remission in Severe Asthma—A Pilot Study

Advances in Respiratory Medicine doi: 10.3390/arm93050037

Authors: Vitaliano Nicola Quaranta Andrea Portacci Leonardo Maselli Marta Tornesello Maria Granito Gennaro Rociola Silvano Dragonieri Giovanna Elisiana Carpagnano

Background: Several studies focused on the importance of managing small airways disease in the treatment of severe asthma, whose improvement can improve respiratory symptoms, lung function, and airways inflammation, potentially reaching the objective of clinical remission. Methods: Twenty-five patients with severe asthma and without bronchiectasis were enrolled. They were started on biological therapies with Omalizumab, Dupilumab, Benralizumab or Mepolizumab. Follow-up evaluations were conducted at baseline (T0) and after one year of biological therapy (T1). Assessments included clinical evaluations, spirometry, questionnaires, and inflammatory markers. Results: Predictive analysis identified baseline FeNO 350 mL/s levels as a significant predictor of clinical remission in both univariable and multivariable analysis. Higher FeNO 350 mL/s levels at T0 were associated with an increased likelihood of achieving remission (p = 0.012). The optimal cutoff value for FeNO 350 mL/s was determined to be 18 ppb, based on the Younden Index. Conclusions: Following patients with severe asthma on biological therapy for one year, FeNO 350 mL/s could be used as a predictive factor of clinical remission, highlighting its importance as inflammatory marker not only in small airways disease, but also in predicting clinical remission in severe asthmatic patients.

]]> FeNO 350 mL/s: Unlocking the Small Airways to Achieve Clinical Remission in Severe Asthma—A Pilot Study Vitaliano Nicola Quaranta Andrea Portacci Leonardo Maselli Marta Tornesello Maria Granito Gennaro Rociola Silvano Dragonieri Giovanna Elisiana Carpagnano doi: 10.3390/arm93050037 Advances in Respiratory Medicine 2025-09-17 Advances in Respiratory Medicine 2025-09-17 93 5 Article 37 10.3390/arm93050037 https://www.mdpi.com/2543-6031/93/5/37 ARM, Vol. 93, Pages 36: Detecting Airway Involvement in Non-Asthmatic Eosinophilic Disorders: Diagnostic Utility of Fractional Exhaled Nitric Oxide (FeNO) https://www.mdpi.com/2543-6031/93/5/36 Airway involvement in eosinophilic disorders other than asthma is not well-defined, and the symptoms may be overshadowed by other more prominent eosinophilic extra-respiratory manifestations. This study aimed to evaluate the utility of fractional exhaled nitric oxide (FeNO) in diagnosing eosinophilic airway involvement in patients with persistent eosinophilia (>0.5 × 109/L). We conducted a retrospective analysis of adult patients with confirmed peripheral blood eosinophilia (>0.5 × 109/L) on at least two occasions one month apart. Patients with blood eosinophilia associated with known eosinophilic airway inflammatory diseases were excluded from the study. Pulmonary function testing, spirometry, and FeNO measurement were conducted. A total of 14 patients with various eosinophil-related disorders were identified, with a mean age of 65.7 years. Increased FeNO levels were associated with airflow obstruction and clinical symptoms such as coughing and wheezing. Notably, eosinophil levels were not predictive of eosinophilic airway involvement. FeNO could be a useful diagnostic tool for detecting bronchial eosinophilic airway inflammation in non-asthmatic disorders, thereby enabling appropriate treatment. Further studies with larger cohorts are needed to validate these findings. 2025-09-16 ARM, Vol. 93, Pages 36: Detecting Airway Involvement in Non-Asthmatic Eosinophilic Disorders: Diagnostic Utility of Fractional Exhaled Nitric Oxide (FeNO)

Advances in Respiratory Medicine doi: 10.3390/arm93050036

Authors: Nicolas Raoul Lucie Laurent Ophélie Ritter Pauline Roux-Claudé Faraj Al Freijat Nadine Magy-Bertrand Virginie Westeel Cindy Barnig

Airway involvement in eosinophilic disorders other than asthma is not well-defined, and the symptoms may be overshadowed by other more prominent eosinophilic extra-respiratory manifestations. This study aimed to evaluate the utility of fractional exhaled nitric oxide (FeNO) in diagnosing eosinophilic airway involvement in patients with persistent eosinophilia (>0.5 × 109/L). We conducted a retrospective analysis of adult patients with confirmed peripheral blood eosinophilia (>0.5 × 109/L) on at least two occasions one month apart. Patients with blood eosinophilia associated with known eosinophilic airway inflammatory diseases were excluded from the study. Pulmonary function testing, spirometry, and FeNO measurement were conducted. A total of 14 patients with various eosinophil-related disorders were identified, with a mean age of 65.7 years. Increased FeNO levels were associated with airflow obstruction and clinical symptoms such as coughing and wheezing. Notably, eosinophil levels were not predictive of eosinophilic airway involvement. FeNO could be a useful diagnostic tool for detecting bronchial eosinophilic airway inflammation in non-asthmatic disorders, thereby enabling appropriate treatment. Further studies with larger cohorts are needed to validate these findings.

]]> Detecting Airway Involvement in Non-Asthmatic Eosinophilic Disorders: Diagnostic Utility of Fractional Exhaled Nitric Oxide (FeNO) Nicolas Raoul Lucie Laurent Ophélie Ritter Pauline Roux-Claudé Faraj Al Freijat Nadine Magy-Bertrand Virginie Westeel Cindy Barnig doi: 10.3390/arm93050036 Advances in Respiratory Medicine 2025-09-16 Advances in Respiratory Medicine 2025-09-16 93 5 Brief Report 36 10.3390/arm93050036 https://www.mdpi.com/2543-6031/93/5/36 ARM, Vol. 93, Pages 35: Bronchial Artery Embolisation in Haemoptysis Management: A Scoping Review with Emphasis on Embolic Materials and Indications https://www.mdpi.com/2543-6031/93/5/35 Haemoptysis is an alarming symptom of a wide spectrum of underlying diseases, ranging from indolent chronic conditions to life-threatening states. Among the strategies to manage pulmonary bleeding is bronchial artery embolisation (BAE), an interventional radiology procedure. The objective of this scoping review was to map the current evidence on embolic agents used in BAE for haemoptysis management, with a focus on their clinical applications, and decision-making factors. Studies published between 2019 and 2024 were included if they specified the embolic material used and reported outcomes of BAE in adult patients. Data were extracted from PubMed and charted according to embolic agent type, recurrence rate, and clinical context. Thirty-one studies met the eligibility criteria. Polyvinyl alcohol (PVA) remains the most widely studied agent, comparable in efficacy to more homogeneous microspheres. Gelatin sponges (GS), though biodegradable, are well-documented and affordable, making them a common choice. N-butyl-2-cyanoacrylate (NBCA) is highly effective for small vessels and may offer lower recurrence rates. Coils are valuable in proximal embolisation and severe cases. This review highlights the need for individualised embolisation strategies and updated guidelines for material selection, considering clinical context, vascular anatomy, and recurrence rates. The findings aim to support evidence-based decision-making in interventional radiology practice. 2025-09-12 ARM, Vol. 93, Pages 35: Bronchial Artery Embolisation in Haemoptysis Management: A Scoping Review with Emphasis on Embolic Materials and Indications

Advances in Respiratory Medicine doi: 10.3390/arm93050035

Authors: Anna Ziętarska Adam Dobek Anna Sawina Piotr Białek Sebastian Majewski Ludomir Stefańczyk

Haemoptysis is an alarming symptom of a wide spectrum of underlying diseases, ranging from indolent chronic conditions to life-threatening states. Among the strategies to manage pulmonary bleeding is bronchial artery embolisation (BAE), an interventional radiology procedure. The objective of this scoping review was to map the current evidence on embolic agents used in BAE for haemoptysis management, with a focus on their clinical applications, and decision-making factors. Studies published between 2019 and 2024 were included if they specified the embolic material used and reported outcomes of BAE in adult patients. Data were extracted from PubMed and charted according to embolic agent type, recurrence rate, and clinical context. Thirty-one studies met the eligibility criteria. Polyvinyl alcohol (PVA) remains the most widely studied agent, comparable in efficacy to more homogeneous microspheres. Gelatin sponges (GS), though biodegradable, are well-documented and affordable, making them a common choice. N-butyl-2-cyanoacrylate (NBCA) is highly effective for small vessels and may offer lower recurrence rates. Coils are valuable in proximal embolisation and severe cases. This review highlights the need for individualised embolisation strategies and updated guidelines for material selection, considering clinical context, vascular anatomy, and recurrence rates. The findings aim to support evidence-based decision-making in interventional radiology practice.

]]> Bronchial Artery Embolisation in Haemoptysis Management: A Scoping Review with Emphasis on Embolic Materials and Indications Anna Ziętarska Adam Dobek Anna Sawina Piotr Białek Sebastian Majewski Ludomir Stefańczyk doi: 10.3390/arm93050035 Advances in Respiratory Medicine 2025-09-12 Advances in Respiratory Medicine 2025-09-12 93 5 Review 35 10.3390/arm93050035 https://www.mdpi.com/2543-6031/93/5/35 ARM, Vol. 93, Pages 34: The Safety and Performance of a Novel Extracorporeal Membrane Oxygenation Device in a Long-Term Ovine Model https://www.mdpi.com/2543-6031/93/5/34 Since extracorporeal membrane oxygenation (ECMO) is primarily used for patients in a high-risk state and is an invasive procedure, its unique application scenarios make it difficult to recruit suitable cases for clinical trials. Therefore, large animal models have become one of the most important models for preclinical evaluation of the safety and effectiveness of ECMO. This study aims to assess the safety and performance of a novel portable ECMO device with Small-tail Han sheep. Fifteen sheep were divided into a test group (LIFEMOTION, Chinabridge, Shenzhen, China) and control group (NOVALUNG XLUNG kit 230, Xonis, Heilbronn, Germany) with veno-venous ECMO (VV-ECMO) and veno-arterial ECMO (VA-ECMO) modes. Tracheal intubation, arteriovenous access, and ECMO support were performed. Vital signs and blood laboratory tests of the subjects were monitored and recorded. The main organs were examined pathologically at the end of day fourteen. The serum protein expression profile was analyzed by protein quantification techniques. All sheep were successfully weaned from ECMO without transfusion or cannula complications. No significant differences were observed between the two groups in terms of vital signs, oxygenation, hemodynamic stability, and physiological function (p > 0.05). According to the serum protein expression profile, no significant biomarkers associated with ECMO clinical complications were identified. The LIFEMOTION ECMO device demonstrated good safety and efficacy. 2025-09-09 ARM, Vol. 93, Pages 34: The Safety and Performance of a Novel Extracorporeal Membrane Oxygenation Device in a Long-Term Ovine Model

Advances in Respiratory Medicine doi: 10.3390/arm93050034

Authors: Yongchao Li Lei Cai Jia Huang Hongbin Gao Zhongqiang Huang Yalun Guan Yunfeng Li Shuhua Liu Shi Liang Summer Xiatian Li Hongzhou Lu Ge Li Yijiang Li Yu Zhang

Since extracorporeal membrane oxygenation (ECMO) is primarily used for patients in a high-risk state and is an invasive procedure, its unique application scenarios make it difficult to recruit suitable cases for clinical trials. Therefore, large animal models have become one of the most important models for preclinical evaluation of the safety and effectiveness of ECMO. This study aims to assess the safety and performance of a novel portable ECMO device with Small-tail Han sheep. Fifteen sheep were divided into a test group (LIFEMOTION, Chinabridge, Shenzhen, China) and control group (NOVALUNG XLUNG kit 230, Xonis, Heilbronn, Germany) with veno-venous ECMO (VV-ECMO) and veno-arterial ECMO (VA-ECMO) modes. Tracheal intubation, arteriovenous access, and ECMO support were performed. Vital signs and blood laboratory tests of the subjects were monitored and recorded. The main organs were examined pathologically at the end of day fourteen. The serum protein expression profile was analyzed by protein quantification techniques. All sheep were successfully weaned from ECMO without transfusion or cannula complications. No significant differences were observed between the two groups in terms of vital signs, oxygenation, hemodynamic stability, and physiological function (p > 0.05). According to the serum protein expression profile, no significant biomarkers associated with ECMO clinical complications were identified. The LIFEMOTION ECMO device demonstrated good safety and efficacy.

]]> The Safety and Performance of a Novel Extracorporeal Membrane Oxygenation Device in a Long-Term Ovine Model Yongchao Li Lei Cai Jia Huang Hongbin Gao Zhongqiang Huang Yalun Guan Yunfeng Li Shuhua Liu Shi Liang Summer Xiatian Li Hongzhou Lu Ge Li Yijiang Li Yu Zhang doi: 10.3390/arm93050034 Advances in Respiratory Medicine 2025-09-09 Advances in Respiratory Medicine 2025-09-09 93 5 Article 34 10.3390/arm93050034 https://www.mdpi.com/2543-6031/93/5/34 ARM, Vol. 93, Pages 33: Test–Retest Reliability and Minimal Detectable Change of the 6-Minute Step Test and 1-Minute Sit-to-Stand Test in Post-COVID-19 Patients https://www.mdpi.com/2543-6031/93/5/33 Background: This study aims to determine test–retest reliability and to calculate minimal detectable change (MDC) scores for the functional capacity of the 6-minute step test (6MST) and 1 min sit-to-stand test (1-min-STST), and compare these outcomes with the 6-minute walk test (6MWT) in post-COVID-19 patients. Methods: A total of 42 post-COVID-19 patients aged 18 years or older were recruited for this study. The post-COVID-19 patients were investigated for cardiovascular response parameters induced by a 6MWT, 6MST, and 1-min-STST on two different days, with a five-day interval between the first and second days. Results: The test–retest reliability obtained between the initial measurement and the measurement recorded five days later in the post-COVID-19 patients was excellent for all three of the 6MWT, 6MST, and 1-min-STST. The ICC of the 6MWT was 0.97 with MDC95 at 5.57%. The ICC of the 6MST was 0.93 with MDC95 at 12.21%, while, the ICC of the 1-min-STST was 0.96 with MDC95 at 3.61%. Conclusions: The 6MST and 1-min-STST were valid and acceptable for the evaluation of functional capacity in post- COVID-19 patients and can be used to investigate whether each post-COVID-19 patient had made significant improvement in a clinical setting. 2025-09-08 ARM, Vol. 93, Pages 33: Test–Retest Reliability and Minimal Detectable Change of the 6-Minute Step Test and 1-Minute Sit-to-Stand Test in Post-COVID-19 Patients

Advances in Respiratory Medicine doi: 10.3390/arm93050033

Authors: Patchareeya Amput Weerasak Tapanya Sirima Wongphon Krittin Naravejsakul Thanakorn Sritiyot

Background: This study aims to determine test–retest reliability and to calculate minimal detectable change (MDC) scores for the functional capacity of the 6-minute step test (6MST) and 1 min sit-to-stand test (1-min-STST), and compare these outcomes with the 6-minute walk test (6MWT) in post-COVID-19 patients. Methods: A total of 42 post-COVID-19 patients aged 18 years or older were recruited for this study. The post-COVID-19 patients were investigated for cardiovascular response parameters induced by a 6MWT, 6MST, and 1-min-STST on two different days, with a five-day interval between the first and second days. Results: The test–retest reliability obtained between the initial measurement and the measurement recorded five days later in the post-COVID-19 patients was excellent for all three of the 6MWT, 6MST, and 1-min-STST. The ICC of the 6MWT was 0.97 with MDC95 at 5.57%. The ICC of the 6MST was 0.93 with MDC95 at 12.21%, while, the ICC of the 1-min-STST was 0.96 with MDC95 at 3.61%. Conclusions: The 6MST and 1-min-STST were valid and acceptable for the evaluation of functional capacity in post- COVID-19 patients and can be used to investigate whether each post-COVID-19 patient had made significant improvement in a clinical setting.

]]> Test–Retest Reliability and Minimal Detectable Change of the 6-Minute Step Test and 1-Minute Sit-to-Stand Test in Post-COVID-19 Patients Patchareeya Amput Weerasak Tapanya Sirima Wongphon Krittin Naravejsakul Thanakorn Sritiyot doi: 10.3390/arm93050033 Advances in Respiratory Medicine 2025-09-08 Advances in Respiratory Medicine 2025-09-08 93 5 Article 33 10.3390/arm93050033 https://www.mdpi.com/2543-6031/93/5/33 ARM, Vol. 93, Pages 32: Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis https://www.mdpi.com/2543-6031/93/5/32 Introduction: Asthma is a chronic airway inflammatory disease characterized by variable airflow limitation and intermittent symptoms. In well-controlled asthma, auscultation and spirometry often appear normal, making diagnosis challenging. Moreover, bronchial provocation tests carry a risk of inducing acute bronchoconstriction. This study aimed to develop a non-invasive, objective, and reproducible diagnostic method using machine learning-based lung sound analysis for the early detection of asthma, even during stable periods. Methods: We designed a machine learning algorithm to classify controlled asthma patients and healthy individuals using respiratory sounds recorded with a digital stethoscope. We enrolled 120 participants (60 asthmatic, 60 healthy). Controlled asthma was defined according to Global Initiative for Asthma (GINA) criteria and was supported by normal spirometry, no pathological auscultation findings, and no exacerbations in the past three months. A total of 3600 respiratory sound segments (each 3 s long) were obtained by dividing 90 s recordings from 120 participants (60 asthmatic, 60 healthy) into non-overlapping clips. The samples were analyzed using Mel-Frequency Cepstral Coefficients (MFCCs) and Tunable Q-Factor Wavelet Transform (TQWT). Significant features selected with ReliefF were used to train Quadratic Support Vector Machine (SVM) and Narrow Neural Network (NNN) models. Results: In 120 participants, pulmonary function test (PFT) results in the asthma group showed lower FEV1 (86.9 ± 5.7%) and FEV1/FVC ratios (86.1 ± 8.8%) compared to controls, but remained within normal ranges. Quadratic SVM achieved 99.86% accuracy, correctly classifying 99.44% of controls and 99.89% of asthma cases. Narrow Neural Network achieved 99.63% accuracy. Sensitivity, specificity, and F1-scores exceeded 99%. Conclusion: This machine learning-based algorithm provides accurate asthma diagnosis, even in patients with normal spirometry and clinical findings, offering a non-invasive and efficient diagnostic tool. 2025-09-04 ARM, Vol. 93, Pages 32: Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis

Advances in Respiratory Medicine doi: 10.3390/arm93050032

Authors: Ihsan Topaloglu Gulfem Ozduygu Cagri Atasoy Guntug Batıhan Damla Serce Gulsah Inanc Mutlu Onur Güçsav Arif Metehan Yıldız Turker Tuncer Sengul Dogan Prabal Datta Barua

Introduction: Asthma is a chronic airway inflammatory disease characterized by variable airflow limitation and intermittent symptoms. In well-controlled asthma, auscultation and spirometry often appear normal, making diagnosis challenging. Moreover, bronchial provocation tests carry a risk of inducing acute bronchoconstriction. This study aimed to develop a non-invasive, objective, and reproducible diagnostic method using machine learning-based lung sound analysis for the early detection of asthma, even during stable periods. Methods: We designed a machine learning algorithm to classify controlled asthma patients and healthy individuals using respiratory sounds recorded with a digital stethoscope. We enrolled 120 participants (60 asthmatic, 60 healthy). Controlled asthma was defined according to Global Initiative for Asthma (GINA) criteria and was supported by normal spirometry, no pathological auscultation findings, and no exacerbations in the past three months. A total of 3600 respiratory sound segments (each 3 s long) were obtained by dividing 90 s recordings from 120 participants (60 asthmatic, 60 healthy) into non-overlapping clips. The samples were analyzed using Mel-Frequency Cepstral Coefficients (MFCCs) and Tunable Q-Factor Wavelet Transform (TQWT). Significant features selected with ReliefF were used to train Quadratic Support Vector Machine (SVM) and Narrow Neural Network (NNN) models. Results: In 120 participants, pulmonary function test (PFT) results in the asthma group showed lower FEV1 (86.9 ± 5.7%) and FEV1/FVC ratios (86.1 ± 8.8%) compared to controls, but remained within normal ranges. Quadratic SVM achieved 99.86% accuracy, correctly classifying 99.44% of controls and 99.89% of asthma cases. Narrow Neural Network achieved 99.63% accuracy. Sensitivity, specificity, and F1-scores exceeded 99%. Conclusion: This machine learning-based algorithm provides accurate asthma diagnosis, even in patients with normal spirometry and clinical findings, offering a non-invasive and efficient diagnostic tool.

]]> Machine Learning-Driven Lung Sound Analysis: Novel Methodology for Asthma Diagnosis Ihsan Topaloglu Gulfem Ozduygu Cagri Atasoy Guntug Batıhan Damla Serce Gulsah Inanc Mutlu Onur Güçsav Arif Metehan Yıldız Turker Tuncer Sengul Dogan Prabal Datta Barua doi: 10.3390/arm93050032 Advances in Respiratory Medicine 2025-09-04 Advances in Respiratory Medicine 2025-09-04 93 5 Article 32 10.3390/arm93050032 https://www.mdpi.com/2543-6031/93/5/32 ARM, Vol. 93, Pages 31: Concomitant Idiopathic Pulmonary Fibrosis and Lung Cancer: An Updated Narrative Review https://www.mdpi.com/2543-6031/93/4/31 Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease (ILD) with poor prognosis and limited therapeutic options. The introduction of antifibrotic agents has improved survival outcomes in IPF patients, which has led to more frequent recognition of comorbidities, particularly lung cancer (LC). This review summarizes current evidence on the epidemiology and pathogenesis of LC in the context of IPF, with particular emphasis placed on shared molecular, cellular, genetic, and epigenetic alterations. Diagnostic approaches and available treatment modalities, including surgical, systemic, and radiation therapies, are outlined, and their limitations in patients with IPF-LC are discussed. Acute exacerbations (AEs), as a life-threatening complication influencing diagnostic and treatment strategies, are specifically addressed. Moreover, studies indicating a possible protective effect of antifibrotic agents against LC development in IPF are reviewed. Further research is warranted into the shared mechanisms of IPF and LC to identify novel therapeutic targets. Establishing standardized, multidisciplinary clinical guidelines is essential for optimizing patient management, reducing AE risk, and improving patient outcomes. 2025-08-18 ARM, Vol. 93, Pages 31: Concomitant Idiopathic Pulmonary Fibrosis and Lung Cancer: An Updated Narrative Review

Advances in Respiratory Medicine doi: 10.3390/arm93040031

Authors: Bartłomiej Czyżak Sebastian Majewski

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease (ILD) with poor prognosis and limited therapeutic options. The introduction of antifibrotic agents has improved survival outcomes in IPF patients, which has led to more frequent recognition of comorbidities, particularly lung cancer (LC). This review summarizes current evidence on the epidemiology and pathogenesis of LC in the context of IPF, with particular emphasis placed on shared molecular, cellular, genetic, and epigenetic alterations. Diagnostic approaches and available treatment modalities, including surgical, systemic, and radiation therapies, are outlined, and their limitations in patients with IPF-LC are discussed. Acute exacerbations (AEs), as a life-threatening complication influencing diagnostic and treatment strategies, are specifically addressed. Moreover, studies indicating a possible protective effect of antifibrotic agents against LC development in IPF are reviewed. Further research is warranted into the shared mechanisms of IPF and LC to identify novel therapeutic targets. Establishing standardized, multidisciplinary clinical guidelines is essential for optimizing patient management, reducing AE risk, and improving patient outcomes.

]]> Concomitant Idiopathic Pulmonary Fibrosis and Lung Cancer: An Updated Narrative Review Bartłomiej Czyżak Sebastian Majewski doi: 10.3390/arm93040031 Advances in Respiratory Medicine 2025-08-18 Advances in Respiratory Medicine 2025-08-18 93 4 Review 31 10.3390/arm93040031 https://www.mdpi.com/2543-6031/93/4/31 ARM, Vol. 93, Pages 30: An Integrated Strategy for Preventing and Rehabilitating Dust-Induced Occupational Bronchopulmonary Diseases: A Scoping Review https://www.mdpi.com/2543-6031/93/4/30 Background: Occupational bronchopulmonary diseases (OBPDs)—including pneumoconiosis, silicosis, and occupational COPD—remain a pressing public health issue, especially in regions with intensive mining, metallurgy, and construction industries. Caused by chronic inhalation of fibrogenic dusts, these conditions are often diagnosed at late stages, resulting in irreversible lung damage and diminished work capacity. Methods: A scoping review was performed using the Arksey and O’Malley framework, with methodological refinements from the Joanna Briggs Institute. Following PRISMA-ScR guidelines, we searched PubMed, Scopus, and gray literature for publications from 2014 to 2024. After screening 1761 records and full-text review, nine studies were included in the final synthesis, comprising two systematic reviews, two narrative literature reviews, and five observational studies. Results: Key risk factors identified included prolonged exposure to silica and coal dust, tobacco use, and genetic susceptibility. Diagnostic delays were attributed to the underuse of high-resolution CT and exhaled nitric oxide analysis. Several studies highlighted the diagnostic value of oxidative stress and inflammatory markers (e.g., IL-6, TNF-α). Nutritional rehabilitation and polyphenol-enriched herbal therapies were associated with improved respiratory function and quality of life. However, these strategies remain underutilized, particularly in low-resource settings. Conclusions: A coordinated, biomarker-driven approach integrating early diagnosis, dust exposure control, and tailored rehabilitation is urgently needed. Multidisciplinary models may reduce the clinical and socioeconomic burden of OBPDs. 2025-08-13 ARM, Vol. 93, Pages 30: An Integrated Strategy for Preventing and Rehabilitating Dust-Induced Occupational Bronchopulmonary Diseases: A Scoping Review

Advances in Respiratory Medicine doi: 10.3390/arm93040030

Authors: Alexandr E. Gulyayev Karlygash S. Absattarova Sayagul A. Kairgeldina Raushan S. Dosmagambetova Kanat K. Tekebayev Madina B. Baurzhan Nazym Sagandykova Gaukhar Sh. Dauletova

Background: Occupational bronchopulmonary diseases (OBPDs)—including pneumoconiosis, silicosis, and occupational COPD—remain a pressing public health issue, especially in regions with intensive mining, metallurgy, and construction industries. Caused by chronic inhalation of fibrogenic dusts, these conditions are often diagnosed at late stages, resulting in irreversible lung damage and diminished work capacity. Methods: A scoping review was performed using the Arksey and O’Malley framework, with methodological refinements from the Joanna Briggs Institute. Following PRISMA-ScR guidelines, we searched PubMed, Scopus, and gray literature for publications from 2014 to 2024. After screening 1761 records and full-text review, nine studies were included in the final synthesis, comprising two systematic reviews, two narrative literature reviews, and five observational studies. Results: Key risk factors identified included prolonged exposure to silica and coal dust, tobacco use, and genetic susceptibility. Diagnostic delays were attributed to the underuse of high-resolution CT and exhaled nitric oxide analysis. Several studies highlighted the diagnostic value of oxidative stress and inflammatory markers (e.g., IL-6, TNF-α). Nutritional rehabilitation and polyphenol-enriched herbal therapies were associated with improved respiratory function and quality of life. However, these strategies remain underutilized, particularly in low-resource settings. Conclusions: A coordinated, biomarker-driven approach integrating early diagnosis, dust exposure control, and tailored rehabilitation is urgently needed. Multidisciplinary models may reduce the clinical and socioeconomic burden of OBPDs.

]]> An Integrated Strategy for Preventing and Rehabilitating Dust-Induced Occupational Bronchopulmonary Diseases: A Scoping Review Alexandr E. Gulyayev Karlygash S. Absattarova Sayagul A. Kairgeldina Raushan S. Dosmagambetova Kanat K. Tekebayev Madina B. Baurzhan Nazym Sagandykova Gaukhar Sh. Dauletova doi: 10.3390/arm93040030 Advances in Respiratory Medicine 2025-08-13 Advances in Respiratory Medicine 2025-08-13 93 4 Review 30 10.3390/arm93040030 https://www.mdpi.com/2543-6031/93/4/30 ARM, Vol. 93, Pages 29: Diagnostic Efficacy of C-Reactive Protein in Differentiating Various Causes of Exudative Pleural Effusion: Disease Research Should Not Be Exclusive to the Wealthy https://www.mdpi.com/2543-6031/93/4/29 Background and Objectives: Discrimination between various causes of exudative pleural effusion (PE) remains a major clinical challenge, and to date, definitive biochemical markers for this discrimination remain lacking. An increasing number of studies have reported that serum C-reactive protein (CRPs), pleural fluid CRP (CRPpf), and CRPpf/CRPs ratio (CRPr) are useful for the differential diagnosis of exudative PE; however, their efficacy rate is not similar in these studies. The majority of these studies were conducted on small groups of subjects, and the efficacy of the gradient between CRPs and CRPpf (CRPg—calculated as CRPs—CRPpf) in this differentiation has not been previously investigated. This study aims to evaluate the efficacy rate of CRPs, CRPpf, CRPg, and CRPr in the differential diagnoses of various causes of exudative PE in a relatively large cohort of patients. Materials and Methods: The research group included 282 subjects with exudative PE—146 had parapneumonic effusion (PPE), 126 had malignant pleural effusion (MPE), and 10 had tuberculous pleural effusion (TPE). The values are presented as mean ± SD. Results: The mean CRPs level was significantly higher in the PPE group compared to the MPE group (p < 0.0001) and the TPE group (p < 0.001), and also significantly higher in the TPE group than in the MPE group (p = 0.0009). Similarly, the mean CRPpf level was significantly higher in the PPE group than in the MPE group (p < 0.0001) and the TPE group (p = 0.04), and also significantly higher in the TPE group than in the MPE group (p < 0.0001). The mean CRPg level was significantly higher in the PPE group than in both the MPE group (p < 0.0001) and the TPE group (p < 0.002). The mean CRPr level did not differ significantly among these groups of exudate. Conclusions: CRPs, CRPpf, and CRPg are effective in the differential diagnosis of exudative PE, while CRPr was not effective in this regard. The main limitation of this study is that the sample size of the TPE group is very small. 2025-08-05 ARM, Vol. 93, Pages 29: Diagnostic Efficacy of C-Reactive Protein in Differentiating Various Causes of Exudative Pleural Effusion: Disease Research Should Not Be Exclusive to the Wealthy

Advances in Respiratory Medicine doi: 10.3390/arm93040029

Authors: Majed Odeh Yana Kogan Edmond Sabo

Background and Objectives: Discrimination between various causes of exudative pleural effusion (PE) remains a major clinical challenge, and to date, definitive biochemical markers for this discrimination remain lacking. An increasing number of studies have reported that serum C-reactive protein (CRPs), pleural fluid CRP (CRPpf), and CRPpf/CRPs ratio (CRPr) are useful for the differential diagnosis of exudative PE; however, their efficacy rate is not similar in these studies. The majority of these studies were conducted on small groups of subjects, and the efficacy of the gradient between CRPs and CRPpf (CRPg—calculated as CRPs—CRPpf) in this differentiation has not been previously investigated. This study aims to evaluate the efficacy rate of CRPs, CRPpf, CRPg, and CRPr in the differential diagnoses of various causes of exudative PE in a relatively large cohort of patients. Materials and Methods: The research group included 282 subjects with exudative PE—146 had parapneumonic effusion (PPE), 126 had malignant pleural effusion (MPE), and 10 had tuberculous pleural effusion (TPE). The values are presented as mean ± SD. Results: The mean CRPs level was significantly higher in the PPE group compared to the MPE group (p < 0.0001) and the TPE group (p < 0.001), and also significantly higher in the TPE group than in the MPE group (p = 0.0009). Similarly, the mean CRPpf level was significantly higher in the PPE group than in the MPE group (p < 0.0001) and the TPE group (p = 0.04), and also significantly higher in the TPE group than in the MPE group (p < 0.0001). The mean CRPg level was significantly higher in the PPE group than in both the MPE group (p < 0.0001) and the TPE group (p < 0.002). The mean CRPr level did not differ significantly among these groups of exudate. Conclusions: CRPs, CRPpf, and CRPg are effective in the differential diagnosis of exudative PE, while CRPr was not effective in this regard. The main limitation of this study is that the sample size of the TPE group is very small.

]]> Diagnostic Efficacy of C-Reactive Protein in Differentiating Various Causes of Exudative Pleural Effusion: Disease Research Should Not Be Exclusive to the Wealthy Majed Odeh Yana Kogan Edmond Sabo doi: 10.3390/arm93040029 Advances in Respiratory Medicine 2025-08-05 Advances in Respiratory Medicine 2025-08-05 93 4 Article 29 10.3390/arm93040029 https://www.mdpi.com/2543-6031/93/4/29 ARM, Vol. 93, Pages 28: Tobacco-Free Schools in Practice: Policy Presence and Enforcement in Baltimore Schools https://www.mdpi.com/2543-6031/93/4/28 Background: School-based tobacco control policies are critical for preventing youth tobacco use. While many districts adopt formal policies to create smoke- and vape-free environments, the degree to which these policies are enforced at the school level may vary, influencing their effectiveness. Little is known about how consistently such policies are implemented across schools within urban school districts. Objectives: This study aimed to examine the existence and enforcement of school-level tobacco control policies in an urban public school system, using Baltimore City schools as a case example. Methods: We conducted a survey of school personnel from 20 high schools in Baltimore City in 2024. The survey instrument assessed the presence and enforcement of policies related to tobacco use prevention, communication, signage, disciplinary actions, and institutional support. Descriptive statistics (frequencies and percentages) were used to summarize responses. Spearman correlations were also used for bivariate correlations. Additional school-level and neighborhood-level contextual data were collected from the internet (neighborhood socioeconomic status and school performance). Results: While many policies existed across the 20 participating schools, their enforcement was widely inconsistent. Most schools reported the existence of policies prohibiting tobacco use in school buildings (60%) and vehicles (55%). However, few schools had visible tobacco-free signage (35%) or offered cessation programs (15%). Communication of policies to students (70%) and staff (65%) was the most commonly enforced aspect of tobacco control policies. Conclusions: Findings suggest that while tobacco control policies may be adopted across urban school systems, their enforcement at the school level remains uneven. Greater attention may be needed to support policy implementation and to reduce variability in school-level practices. Baltimore City serves as a useful case study to understand these challenges and identify opportunities for strengthening school-based tobacco prevention efforts. 2025-08-05 ARM, Vol. 93, Pages 28: Tobacco-Free Schools in Practice: Policy Presence and Enforcement in Baltimore Schools

Advances in Respiratory Medicine doi: 10.3390/arm93040028

Authors: Chidubem Egboluche Rifath Ara Alam Barsha Shervin Assari Michelle Mercure Marc Laveau Oluwatosin Olateju Payam Sheikhattari

Background: School-based tobacco control policies are critical for preventing youth tobacco use. While many districts adopt formal policies to create smoke- and vape-free environments, the degree to which these policies are enforced at the school level may vary, influencing their effectiveness. Little is known about how consistently such policies are implemented across schools within urban school districts. Objectives: This study aimed to examine the existence and enforcement of school-level tobacco control policies in an urban public school system, using Baltimore City schools as a case example. Methods: We conducted a survey of school personnel from 20 high schools in Baltimore City in 2024. The survey instrument assessed the presence and enforcement of policies related to tobacco use prevention, communication, signage, disciplinary actions, and institutional support. Descriptive statistics (frequencies and percentages) were used to summarize responses. Spearman correlations were also used for bivariate correlations. Additional school-level and neighborhood-level contextual data were collected from the internet (neighborhood socioeconomic status and school performance). Results: While many policies existed across the 20 participating schools, their enforcement was widely inconsistent. Most schools reported the existence of policies prohibiting tobacco use in school buildings (60%) and vehicles (55%). However, few schools had visible tobacco-free signage (35%) or offered cessation programs (15%). Communication of policies to students (70%) and staff (65%) was the most commonly enforced aspect of tobacco control policies. Conclusions: Findings suggest that while tobacco control policies may be adopted across urban school systems, their enforcement at the school level remains uneven. Greater attention may be needed to support policy implementation and to reduce variability in school-level practices. Baltimore City serves as a useful case study to understand these challenges and identify opportunities for strengthening school-based tobacco prevention efforts.

]]> Tobacco-Free Schools in Practice: Policy Presence and Enforcement in Baltimore Schools Chidubem Egboluche Rifath Ara Alam Barsha Shervin Assari Michelle Mercure Marc Laveau Oluwatosin Olateju Payam Sheikhattari doi: 10.3390/arm93040028 Advances in Respiratory Medicine 2025-08-05 Advances in Respiratory Medicine 2025-08-05 93 4 Article 28 10.3390/arm93040028 https://www.mdpi.com/2543-6031/93/4/28 ARM, Vol. 93, Pages 27: RSPH4A-PCDx: An Index to Predict Lung Function Decline in Primary Ciliary Dyskinesia https://www.mdpi.com/2543-6031/93/4/27 Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that impairs mucociliary clearance and leads to progressive lung disease. This study aimed to characterize lung function decline in a genetically homogeneous cohort of Puerto Rican patients with RSPH4A-associated PCD and to develop a clinical tool to predict lung function decline and support transplant referral decisions. We conducted a retrospective chart review of patients (n = 25) with a confirmed RSPH4A [c.921+3_6delAAGT] genetic variant, collecting longitudinal spirometry data and applying linear regressions to calculate each patient’s individual FEV1 decline. The median FEV1 at diagnosis was 55%, with a median annual decline of −0.75% predicted. Adults exhibited significantly lower lung function compared to pediatric patients, while no difference was seen between males and females. Based on this observed decline, we developed the Predicted Capacity Decline Index (PCDx), an index that estimates the age and time until a patient reaches the 30% FEV1 threshold, the point at which lung transplant referral is typically considered. Our findings underscore the need for early intervention and suggest that genotype-specific tools like the PCDx may enhance clinical decision-making in managing progressive lung disease in PCD. 2025-08-02 ARM, Vol. 93, Pages 27: RSPH4A-PCDx: An Index to Predict Lung Function Decline in Primary Ciliary Dyskinesia

Advances in Respiratory Medicine doi: 10.3390/arm93040027

Authors: Gabriel Román-Ríos Gabriel Rosario-Ortiz Marcos J. Ramos-Benitez Ricardo A. Mosquera Wilfredo De Jesús-Rojas

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that impairs mucociliary clearance and leads to progressive lung disease. This study aimed to characterize lung function decline in a genetically homogeneous cohort of Puerto Rican patients with RSPH4A-associated PCD and to develop a clinical tool to predict lung function decline and support transplant referral decisions. We conducted a retrospective chart review of patients (n = 25) with a confirmed RSPH4A [c.921+3_6delAAGT] genetic variant, collecting longitudinal spirometry data and applying linear regressions to calculate each patient’s individual FEV1 decline. The median FEV1 at diagnosis was 55%, with a median annual decline of −0.75% predicted. Adults exhibited significantly lower lung function compared to pediatric patients, while no difference was seen between males and females. Based on this observed decline, we developed the Predicted Capacity Decline Index (PCDx), an index that estimates the age and time until a patient reaches the 30% FEV1 threshold, the point at which lung transplant referral is typically considered. Our findings underscore the need for early intervention and suggest that genotype-specific tools like the PCDx may enhance clinical decision-making in managing progressive lung disease in PCD.

]]> RSPH4A-PCDx: An Index to Predict Lung Function Decline in Primary Ciliary Dyskinesia Gabriel Román-Ríos Gabriel Rosario-Ortiz Marcos J. Ramos-Benitez Ricardo A. Mosquera Wilfredo De Jesús-Rojas doi: 10.3390/arm93040027 Advances in Respiratory Medicine 2025-08-02 Advances in Respiratory Medicine 2025-08-02 93 4 Article 27 10.3390/arm93040027 https://www.mdpi.com/2543-6031/93/4/27 ARM, Vol. 93, Pages 26: Investigation of Individual Variability and Temporal Fluctuations in Exhaled Nitric Oxide (FeNO) Levels in Healthy Individuals https://www.mdpi.com/2543-6031/93/4/26 Measurement of nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, non-invasive, simple, and safe method for assessing airway inflammation. It serves as a complementary tool to other methods for evaluating airway diseases. However, little is known about the typical NO levels in healthy individuals, including individual differences and the influence of measurement timing. Therefore, this study classified measurement times into four periods and statistically analyzed NO levels in healthy individuals. The mean values among groups were compared using repeated measures ANOVA on six participants. The analysis showed large individual variations in NO levels, resulting in no significant difference (p = 0.29). Notably, greater fluctuations were observed in the morning. These findings align with previous studies suggesting the influence of circadian rhythms and the redundancy of repeated measurements. This study highlights the need to consider timing and individual variability when using FeNO as a physiological marker in healthy populations. 2025-07-21 ARM, Vol. 93, Pages 26: Investigation of Individual Variability and Temporal Fluctuations in Exhaled Nitric Oxide (FeNO) Levels in Healthy Individuals

Advances in Respiratory Medicine doi: 10.3390/arm93040026

Authors: Emi Yuda Tomoki Ando Yukihiro Ishida Hiroyuki Sakano Yutaka Yoshida

Measurement of nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, non-invasive, simple, and safe method for assessing airway inflammation. It serves as a complementary tool to other methods for evaluating airway diseases. However, little is known about the typical NO levels in healthy individuals, including individual differences and the influence of measurement timing. Therefore, this study classified measurement times into four periods and statistically analyzed NO levels in healthy individuals. The mean values among groups were compared using repeated measures ANOVA on six participants. The analysis showed large individual variations in NO levels, resulting in no significant difference (p = 0.29). Notably, greater fluctuations were observed in the morning. These findings align with previous studies suggesting the influence of circadian rhythms and the redundancy of repeated measurements. This study highlights the need to consider timing and individual variability when using FeNO as a physiological marker in healthy populations.

]]> Investigation of Individual Variability and Temporal Fluctuations in Exhaled Nitric Oxide (FeNO) Levels in Healthy Individuals Emi Yuda Tomoki Ando Yukihiro Ishida Hiroyuki Sakano Yutaka Yoshida doi: 10.3390/arm93040026 Advances in Respiratory Medicine 2025-07-21 Advances in Respiratory Medicine 2025-07-21 93 4 Article 26 10.3390/arm93040026 https://www.mdpi.com/2543-6031/93/4/26 ARM, Vol. 93, Pages 25: A Comparison of Impulse Oscillometry and Spirometry by Percent Predicted in Identifying Uncontrolled Asthma https://www.mdpi.com/2543-6031/93/4/25 Background: The role of impulse oscillometry (IOS) in evaluating asthma control remains a challenge because the interpretation varies by many factors, including ethnicity. We aimed to assess the diagnostic contribution of spirometry and IOS, established from reference equations, in the detection of uncontrolled asthma. Methods: This retrospective study was conducted in adult asthma subjects with normal spirometry. Uncontrolled asthma was defined as an Asthma Control Test (ACT) score ≤ 19. Receiver operating characteristic (ROC) curves were plotted to compare the diagnostic abilities of the %-predicted of heterogeneity of resistance at 5 Hz and 20 Hz (R5-R20) and the %-predicted of forced expiratory volume in the first second (FEV1) in detecting uncontrolled asthma. Multivariable risk regressions were performed to identify the %-predicted of R5-R20 as a predictor for uncontrolled asthma. Results: The %-predicted of R5-R20 demonstrated a superior diagnostic ability for detecting uncontrolled asthma compared to the %-predicted FEV1, with the area under the ROC curves (AuROC) = 0.939 vs. 0.712, respectively, p < 0.001. The %-predicted R5R20 of ≥200 showed the highest AuROC for detecting uncontrolled asthma with an adjusted risk ratio of 10.86 (95%CI; 3.77, 31.29; p < 0.001). Conclusions: IOS demonstrated better diagnostic ability for detecting uncontrolled asthma than spirometry. 2025-07-18 ARM, Vol. 93, Pages 25: A Comparison of Impulse Oscillometry and Spirometry by Percent Predicted in Identifying Uncontrolled Asthma

Advances in Respiratory Medicine doi: 10.3390/arm93040025

Authors: Chalerm Liwsrisakun Chaicharn Pothirat Athavudh Deesomchok Pilaiporn Duangjit Warawut Chaiwong

Background: The role of impulse oscillometry (IOS) in evaluating asthma control remains a challenge because the interpretation varies by many factors, including ethnicity. We aimed to assess the diagnostic contribution of spirometry and IOS, established from reference equations, in the detection of uncontrolled asthma. Methods: This retrospective study was conducted in adult asthma subjects with normal spirometry. Uncontrolled asthma was defined as an Asthma Control Test (ACT) score ≤ 19. Receiver operating characteristic (ROC) curves were plotted to compare the diagnostic abilities of the %-predicted of heterogeneity of resistance at 5 Hz and 20 Hz (R5-R20) and the %-predicted of forced expiratory volume in the first second (FEV1) in detecting uncontrolled asthma. Multivariable risk regressions were performed to identify the %-predicted of R5-R20 as a predictor for uncontrolled asthma. Results: The %-predicted of R5-R20 demonstrated a superior diagnostic ability for detecting uncontrolled asthma compared to the %-predicted FEV1, with the area under the ROC curves (AuROC) = 0.939 vs. 0.712, respectively, p < 0.001. The %-predicted R5R20 of ≥200 showed the highest AuROC for detecting uncontrolled asthma with an adjusted risk ratio of 10.86 (95%CI; 3.77, 31.29; p < 0.001). Conclusions: IOS demonstrated better diagnostic ability for detecting uncontrolled asthma than spirometry.

]]> A Comparison of Impulse Oscillometry and Spirometry by Percent Predicted in Identifying Uncontrolled Asthma Chalerm Liwsrisakun Chaicharn Pothirat Athavudh Deesomchok Pilaiporn Duangjit Warawut Chaiwong doi: 10.3390/arm93040025 Advances in Respiratory Medicine 2025-07-18 Advances in Respiratory Medicine 2025-07-18 93 4 Article 25 10.3390/arm93040025 https://www.mdpi.com/2543-6031/93/4/25 ARM, Vol. 93, Pages 24: Pharmacological Immunomodulation via Collagen–Polyvinylpyrrolidone or Pirfenidone Plays a Role in the Recovery of Patients with Severe COVID-19 Through Similar Mechanisms of Action Involving the JAK/STAT Signalling Pathway: A Pilot Study https://www.mdpi.com/2543-6031/93/4/24 The therapeutic target of COVID-19 is focused on controlling inflammation and preventing fibrosis. Collagen–polyvinylpyrrolidone (collagen-PVP) and pirfenidone both have the ability to control the cytokine storm observed in rheumatic and fibrotic disorders. In this work, our aim was to understand the benefits of treatment with each of these drugs in patients with severe COVID-19. In total, 36 patients were treated with dexamethasone and enoxaparin, but 26 were allocated collagen-PVP or pirfenidone (n = 15 and 11, respectively); the clinical and metabolic effects were compared among them. Since pirfenidone works via transcriptional mechanisms, we performed a human genome microarray assay using RNA isolated from fibroblast and monocyte cultures treated with the biodrug, with the aim of hypothesising a possible mechanism of action for collagen-PVP. Our results showed that hospital stay duration, quick COVID-19 severity index (qCSI), and admission to the intensive care unit were statistically significantly lower (p < 0.02) in patients treated with collagen-PVP or pirfenidone when compared with the control group, and that only collagen-PVP normalised serum glucose at discharge. Ingenuity Pathway Analysis showed that the cell cycle, inflammation, and cell surface–extracellular matrix interactions could be regulated with collagen-PVP via the downmodulation of proinflammatory cytokines, while Th2 anti-inflammatory response signalling could be upregulated. Furthermore, the downregulation of some of the genes involved in nitric oxide production showed a possible control for JAK in the IFN-γ pathway, allowing for the possibility of controlling inflammation through the JAK/STAT pathway, as has been observed for pirfenidone and other immunomodulators, such as ruxolitinib. 2025-07-18 ARM, Vol. 93, Pages 24: Pharmacological Immunomodulation via Collagen–Polyvinylpyrrolidone or Pirfenidone Plays a Role in the Recovery of Patients with Severe COVID-19 Through Similar Mechanisms of Action Involving the JAK/STAT Signalling Pathway: A Pilot Study

Advances in Respiratory Medicine doi: 10.3390/arm93040024

Authors: Hugo Mendieta-Zerón Esteban Cruz-Arenas Salvador Díaz-Meza Alejandro Cabrera-Wrooman Edna Ayerim Mandujano-Tinoco Rosa M. Salgado Hugo Tovar Daniel Muñiz-García Laura Julieta Orozco-Castañeda Sonia Hernández-Enríquez Miriam Deyanira Rodríguez-Piña Ana Sarahí Mulia-Soto José Meneses-Calderón Paul Mondragón-Terán Edgar Krötzsch

The therapeutic target of COVID-19 is focused on controlling inflammation and preventing fibrosis. Collagen–polyvinylpyrrolidone (collagen-PVP) and pirfenidone both have the ability to control the cytokine storm observed in rheumatic and fibrotic disorders. In this work, our aim was to understand the benefits of treatment with each of these drugs in patients with severe COVID-19. In total, 36 patients were treated with dexamethasone and enoxaparin, but 26 were allocated collagen-PVP or pirfenidone (n = 15 and 11, respectively); the clinical and metabolic effects were compared among them. Since pirfenidone works via transcriptional mechanisms, we performed a human genome microarray assay using RNA isolated from fibroblast and monocyte cultures treated with the biodrug, with the aim of hypothesising a possible mechanism of action for collagen-PVP. Our results showed that hospital stay duration, quick COVID-19 severity index (qCSI), and admission to the intensive care unit were statistically significantly lower (p < 0.02) in patients treated with collagen-PVP or pirfenidone when compared with the control group, and that only collagen-PVP normalised serum glucose at discharge. Ingenuity Pathway Analysis showed that the cell cycle, inflammation, and cell surface–extracellular matrix interactions could be regulated with collagen-PVP via the downmodulation of proinflammatory cytokines, while Th2 anti-inflammatory response signalling could be upregulated. Furthermore, the downregulation of some of the genes involved in nitric oxide production showed a possible control for JAK in the IFN-γ pathway, allowing for the possibility of controlling inflammation through the JAK/STAT pathway, as has been observed for pirfenidone and other immunomodulators, such as ruxolitinib.

]]> Pharmacological Immunomodulation via Collagen–Polyvinylpyrrolidone or Pirfenidone Plays a Role in the Recovery of Patients with Severe COVID-19 Through Similar Mechanisms of Action Involving the JAK/STAT Signalling Pathway: A Pilot Study Hugo Mendieta-Zerón Esteban Cruz-Arenas Salvador Díaz-Meza Alejandro Cabrera-Wrooman Edna Ayerim Mandujano-Tinoco Rosa M. Salgado Hugo Tovar Daniel Muñiz-García Laura Julieta Orozco-Castañeda Sonia Hernández-Enríquez Miriam Deyanira Rodríguez-Piña Ana Sarahí Mulia-Soto José Meneses-Calderón Paul Mondragón-Terán Edgar Krötzsch doi: 10.3390/arm93040024 Advances in Respiratory Medicine 2025-07-18 Advances in Respiratory Medicine 2025-07-18 93 4 Article 24 10.3390/arm93040024 https://www.mdpi.com/2543-6031/93/4/24 ARM, Vol. 93, Pages 23: Impact of Invasive Mechanical Ventilation on the Lung Microbiome https://www.mdpi.com/2543-6031/93/4/23 The lung microbiota is integral to maintaining microenvironmental homeostasis, influencing immune regulation, host defense against pathogens, and overall respiratory health. The dynamic interplay among the lung microbiota emphasizes their significance in shaping the respiratory milieu and potential impact on diverse pulmonary affections. This investigation aimed to identify the effects of invasive mechanical ventilation on the lung microbiome. Materials and Methods: A systematic review was conducted with registration number CRD42023461618, based on a search of PubMed, SCOPUS, and Web of Science databases, in line with the PRISMA guidelines. To achieve this, “(mechanical ventilation) AND (microbiota)” was used as the search term, replicable across all databases. The closing date of the search was 12 March 2025, and the evidence was scored using the MINORS scale. Results: A total of 16 studies were included, with patients aged 13.6 months to 76 years, predominantly male (64.2%). Common ICU admission diagnoses requiring invasive mechanical ventilation (IMV) included pneumonia, acute respiratory failure, and COVID-19. IMV was associated with reduced lung microbiota diversity and an increased prevalence of pathogenic bacteria, including Prevotella, Streptococcus, Staphylococcus, Pseudomonas, and Acinetobacter. The most frequently used antibiotics were cephalosporins, aminoglycosides, and penicillins. IMV-induced pulmonary dysbiosis correlated with higher infection risk and mortality, particularly in pneumonia and COVID-19 cases. Factors such as antimicrobial therapy, enteral nutrition, and systemic inflammation contributed to these alterations. Conclusions: Invasive mechanical ventilation has been associated with the development of alterations in the respiratory microbiome, resulting in reduced diversity of lung microorganisms. 2025-07-01 ARM, Vol. 93, Pages 23: Impact of Invasive Mechanical Ventilation on the Lung Microbiome

Advances in Respiratory Medicine doi: 10.3390/arm93040023

Authors: Jose Luis Estela-Zape Valeria Sanclemente-Cardoza Maria Alejandra Espinosa-Cifuentes Leidy Tatiana Ordoñez-Mora

The lung microbiota is integral to maintaining microenvironmental homeostasis, influencing immune regulation, host defense against pathogens, and overall respiratory health. The dynamic interplay among the lung microbiota emphasizes their significance in shaping the respiratory milieu and potential impact on diverse pulmonary affections. This investigation aimed to identify the effects of invasive mechanical ventilation on the lung microbiome. Materials and Methods: A systematic review was conducted with registration number CRD42023461618, based on a search of PubMed, SCOPUS, and Web of Science databases, in line with the PRISMA guidelines. To achieve this, “(mechanical ventilation) AND (microbiota)” was used as the search term, replicable across all databases. The closing date of the search was 12 March 2025, and the evidence was scored using the MINORS scale. Results: A total of 16 studies were included, with patients aged 13.6 months to 76 years, predominantly male (64.2%). Common ICU admission diagnoses requiring invasive mechanical ventilation (IMV) included pneumonia, acute respiratory failure, and COVID-19. IMV was associated with reduced lung microbiota diversity and an increased prevalence of pathogenic bacteria, including Prevotella, Streptococcus, Staphylococcus, Pseudomonas, and Acinetobacter. The most frequently used antibiotics were cephalosporins, aminoglycosides, and penicillins. IMV-induced pulmonary dysbiosis correlated with higher infection risk and mortality, particularly in pneumonia and COVID-19 cases. Factors such as antimicrobial therapy, enteral nutrition, and systemic inflammation contributed to these alterations. Conclusions: Invasive mechanical ventilation has been associated with the development of alterations in the respiratory microbiome, resulting in reduced diversity of lung microorganisms.

]]> Impact of Invasive Mechanical Ventilation on the Lung Microbiome Jose Luis Estela-Zape Valeria Sanclemente-Cardoza Maria Alejandra Espinosa-Cifuentes Leidy Tatiana Ordoñez-Mora doi: 10.3390/arm93040023 Advances in Respiratory Medicine 2025-07-01 Advances in Respiratory Medicine 2025-07-01 93 4 Review 23 10.3390/arm93040023 https://www.mdpi.com/2543-6031/93/4/23 ARM, Vol. 93, Pages 22: Imaging and Laboratory Results as Predictors of the Course of COVID-19 https://www.mdpi.com/2543-6031/93/4/22 Background: COVID-19 most often affects the respiratory system and may manifest as acute respiratory failure requiring the use of non-invasive respiratory support (NIRS). The aim of this study was to find predictors based on laboratory results and chest computed tomography (CT) scans performed on admission to the hospital indicating the need for NIRS and predicting mortality after hospital discharge. Methods: We retrospectively analysed data from consecutive patients hospitalised in the Pulmonology Department of the Temporary COVID Hospital in Poznan from 1 February 2021 to 31 March 2022. Upon admission to the department, the patients underwent a series of laboratory blood tests and high-resolution chest CT scan. Results: The study group included 282 patients, with an average age of 60.0 ± 15.0 years. In total, 54 (53%) patients of 101 requiring NIRS died from various causes or required intubation. Patients who required NIRS were significantly older and had more severe changes in the lung parenchyma. They had higher white blood cell and neutrophil counts and lower lymphocyte counts, as well as higher concentrations of D-dimer, CRP, PCT, and IL-6 and greater activities of LDH and AST. Conclusions: Laboratory tests and chest CT performed on hospital admission may be useful to rapidly identify patients at higher risk for severe disease. 2025-07-01 ARM, Vol. 93, Pages 22: Imaging and Laboratory Results as Predictors of the Course of COVID-19

Advances in Respiratory Medicine doi: 10.3390/arm93040022

Authors: Ewelina Tobiczyk Hanna Maria Winiarska Daria Springer Aleksandra Ludziejewska Ewa Wysocka Szymon Skoczyński Szczepan Cofta

Background: COVID-19 most often affects the respiratory system and may manifest as acute respiratory failure requiring the use of non-invasive respiratory support (NIRS). The aim of this study was to find predictors based on laboratory results and chest computed tomography (CT) scans performed on admission to the hospital indicating the need for NIRS and predicting mortality after hospital discharge. Methods: We retrospectively analysed data from consecutive patients hospitalised in the Pulmonology Department of the Temporary COVID Hospital in Poznan from 1 February 2021 to 31 March 2022. Upon admission to the department, the patients underwent a series of laboratory blood tests and high-resolution chest CT scan. Results: The study group included 282 patients, with an average age of 60.0 ± 15.0 years. In total, 54 (53%) patients of 101 requiring NIRS died from various causes or required intubation. Patients who required NIRS were significantly older and had more severe changes in the lung parenchyma. They had higher white blood cell and neutrophil counts and lower lymphocyte counts, as well as higher concentrations of D-dimer, CRP, PCT, and IL-6 and greater activities of LDH and AST. Conclusions: Laboratory tests and chest CT performed on hospital admission may be useful to rapidly identify patients at higher risk for severe disease.

]]> Imaging and Laboratory Results as Predictors of the Course of COVID-19 Ewelina Tobiczyk Hanna Maria Winiarska Daria Springer Aleksandra Ludziejewska Ewa Wysocka Szymon Skoczyński Szczepan Cofta doi: 10.3390/arm93040022 Advances in Respiratory Medicine 2025-07-01 Advances in Respiratory Medicine 2025-07-01 93 4 Article 22 10.3390/arm93040022 https://www.mdpi.com/2543-6031/93/4/22 ARM, Vol. 93, Pages 21: The Comparative Effectiveness of Mepolizumab and Benralizumab in the Treatment of Eosinophilic Asthma https://www.mdpi.com/2543-6031/93/4/21 Background: Severe asthma is associated with significant morbidity and risk of complications. Some patients, suffering from eosinophilic asthma, may benefit from biological therapies, especially anti IL-5 (anti-interleukin-5). The purpose of the study was to compare the efficacy evaluation of mepolizumab and benralizumab in the treatment of eosinophilic asthma. Methods: A retrospective, single-centre study including 59 patients with severe eosinophilic asthma treated with biologics (mepolizumab and benralizumab). Clinical outcomes, including peripheral blood morphotic characteristics, spirometry parameters, asthma control questionnaire (ACQ), mini-Asthma Quality of Life Questionnaire (mini-AQLQ) scores, daily oral corticosteroid use, body mass index, exacerbation rate, and exercise tolerance, were examined at the beginning and after 6 months of biological treatment. Results: A total of 38 patients were treated with mepolizumab and 21 with benralizumab. Significant improvements (p < 0.05) in eosinophil count, required daily dose of glucocorticoids, ACQ, mini-AQLQ scores, and exacerbation rate were observed in both groups after six months of treatment. There was no statistical difference (p < 0.05) in the abovementioned parameters between the groups. Conclusions: In patients with severe eosinophilic asthma, mepolizumab and benralizumab were associated with significant improvements in clinical state. Patients with type 2 asthma will benefit from the therapy with both anti-IL5 biologic drugs. 2025-06-20 ARM, Vol. 93, Pages 21: The Comparative Effectiveness of Mepolizumab and Benralizumab in the Treatment of Eosinophilic Asthma

Advances in Respiratory Medicine doi: 10.3390/arm93040021

Authors: Aleksandra Niemiec-Górska Olga Branicka Paula Olszewska Sylwia Mielcarska Joanna Glück Barbara Rymarczyk Radosław Gawlik

Background: Severe asthma is associated with significant morbidity and risk of complications. Some patients, suffering from eosinophilic asthma, may benefit from biological therapies, especially anti IL-5 (anti-interleukin-5). The purpose of the study was to compare the efficacy evaluation of mepolizumab and benralizumab in the treatment of eosinophilic asthma. Methods: A retrospective, single-centre study including 59 patients with severe eosinophilic asthma treated with biologics (mepolizumab and benralizumab). Clinical outcomes, including peripheral blood morphotic characteristics, spirometry parameters, asthma control questionnaire (ACQ), mini-Asthma Quality of Life Questionnaire (mini-AQLQ) scores, daily oral corticosteroid use, body mass index, exacerbation rate, and exercise tolerance, were examined at the beginning and after 6 months of biological treatment. Results: A total of 38 patients were treated with mepolizumab and 21 with benralizumab. Significant improvements (p < 0.05) in eosinophil count, required daily dose of glucocorticoids, ACQ, mini-AQLQ scores, and exacerbation rate were observed in both groups after six months of treatment. There was no statistical difference (p < 0.05) in the abovementioned parameters between the groups. Conclusions: In patients with severe eosinophilic asthma, mepolizumab and benralizumab were associated with significant improvements in clinical state. Patients with type 2 asthma will benefit from the therapy with both anti-IL5 biologic drugs.

]]> The Comparative Effectiveness of Mepolizumab and Benralizumab in the Treatment of Eosinophilic Asthma Aleksandra Niemiec-Górska Olga Branicka Paula Olszewska Sylwia Mielcarska Joanna Glück Barbara Rymarczyk Radosław Gawlik doi: 10.3390/arm93040021 Advances in Respiratory Medicine 2025-06-20 Advances in Respiratory Medicine 2025-06-20 93 4 Article 21 10.3390/arm93040021 https://www.mdpi.com/2543-6031/93/4/21 ARM, Vol. 93, Pages 20: Evaluating Obstructive Sleep Apnea Utilizing Arterial Tonometry in Individuals with Cystic Fibrosis https://www.mdpi.com/2543-6031/93/3/20 Poor sleep quality and excessive daytime sleepiness are commonly reported by individuals with cystic fibrosis. The potential impact of comorbid sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA), has not been extensively studied in the CF population. At present, there are no specific recommendations available to help clinicians identify patients with CF who are at increased risk of sleep disorders. Home sleep apnea testing using a validated peripheral arterial tonometry (PAT) device may offer an accurate diagnosis of OSA in a more convenient and low-cost method than in-lab polysomnography. In this single-center study of 19 adults with CF, we found an increased prevalence of OSA among individuals with CF compared to general population estimates. Although associations with an FEV < 70% predicted and a modified Mallampati score ≥ 3 were observed, these odds ratios did not reach statistical significance, likely reflecting limited power in this small pilot sample. There was no association found between the self-reported presence of nocturnal cough or snoring and OSA. We also found no association between OSA and abnormal scores on commonly used, validated sleep questionnaires, suggesting that CF-specific scales may be needed for effective screening in the CF clinic. 2025-06-17 ARM, Vol. 93, Pages 20: Evaluating Obstructive Sleep Apnea Utilizing Arterial Tonometry in Individuals with Cystic Fibrosis

Advances in Respiratory Medicine doi: 10.3390/arm93030020

Authors: Michelle Chiu Bethany Bartley Elizabeth Gootkind Salma Batool-Anwar Donald G. Keamy Thomas Bernard Kinane Lael M. Yonker Kevin S. Gipson

Poor sleep quality and excessive daytime sleepiness are commonly reported by individuals with cystic fibrosis. The potential impact of comorbid sleep-disordered breathing (SDB), particularly obstructive sleep apnea (OSA), has not been extensively studied in the CF population. At present, there are no specific recommendations available to help clinicians identify patients with CF who are at increased risk of sleep disorders. Home sleep apnea testing using a validated peripheral arterial tonometry (PAT) device may offer an accurate diagnosis of OSA in a more convenient and low-cost method than in-lab polysomnography. In this single-center study of 19 adults with CF, we found an increased prevalence of OSA among individuals with CF compared to general population estimates. Although associations with an FEV < 70% predicted and a modified Mallampati score ≥ 3 were observed, these odds ratios did not reach statistical significance, likely reflecting limited power in this small pilot sample. There was no association found between the self-reported presence of nocturnal cough or snoring and OSA. We also found no association between OSA and abnormal scores on commonly used, validated sleep questionnaires, suggesting that CF-specific scales may be needed for effective screening in the CF clinic.

]]> Evaluating Obstructive Sleep Apnea Utilizing Arterial Tonometry in Individuals with Cystic Fibrosis Michelle Chiu Bethany Bartley Elizabeth Gootkind Salma Batool-Anwar Donald G. Keamy Thomas Bernard Kinane Lael M. Yonker Kevin S. Gipson doi: 10.3390/arm93030020 Advances in Respiratory Medicine 2025-06-17 Advances in Respiratory Medicine 2025-06-17 93 3 Article 20 10.3390/arm93030020 https://www.mdpi.com/2543-6031/93/3/20 ARM, Vol. 93, Pages 19: Harnessing Natural Product Compounds to Target Dormancy Survival Regulator (DosR) in Latent Tuberculosis Infection (LTBI): An In Silico Strategy Against Dormancy https://www.mdpi.com/2543-6031/93/3/19 Dormancy occurs when Mycobacterium tuberculosis (Mtb) enters a non-replicating and metabolically inactive state in response to hostile environment. During this state, it is highly resistant to conventional antibiotics, which increase the urgency to develop new potential drugs against dormant bacilli. In view of this, the dormancy survival regulator (DosR) protein is thought to be an essential component that plays a key role in bacterial adaptation to dormancy during hypoxic conditions. Herein, the NP-lib database containing natural product compounds was screened virtually against the binding site of the DosR protein using the MTiopen screen web server. A series of computational analyses were performed, including redocking, intermolecular interaction analysis, and MDS, followed by binding free energy analysis. Through screening, 1000 natural product compounds were obtained with docking energy ranging from −8.5 to −4.1 kcal/mol. The top four lead compounds were then selected for further investigation. On comparative analysis of intermolecular interaction, dynamics simulation and MM/GBSA calculation revealed that M3 docked with the DosR protein (docking score = −8.1 kcal/mol, RMSD = ~7 Å and ΔG Bind = −53.51 kcal/mol) exhibited stronger stability than reference compound Ursolic acid (docking score = −6.2 kcal/mol, RMSD = ~13.5 Å and ΔG Bind = −44.51 kcal/mol). Hence, M3 is recommended for further validation through in vitro and in vivo studies against latent tuberculosis infection. 2025-06-16 ARM, Vol. 93, Pages 19: Harnessing Natural Product Compounds to Target Dormancy Survival Regulator (DosR) in Latent Tuberculosis Infection (LTBI): An In Silico Strategy Against Dormancy

Advances in Respiratory Medicine doi: 10.3390/arm93030019

Authors: Mandeep Chouhan Mukesh Kumar Vivek Dhar Dwivedi Vivek Kumar Kashyap Himanshu Narayan Singh Sanjay Kumar

Dormancy occurs when Mycobacterium tuberculosis (Mtb) enters a non-replicating and metabolically inactive state in response to hostile environment. During this state, it is highly resistant to conventional antibiotics, which increase the urgency to develop new potential drugs against dormant bacilli. In view of this, the dormancy survival regulator (DosR) protein is thought to be an essential component that plays a key role in bacterial adaptation to dormancy during hypoxic conditions. Herein, the NP-lib database containing natural product compounds was screened virtually against the binding site of the DosR protein using the MTiopen screen web server. A series of computational analyses were performed, including redocking, intermolecular interaction analysis, and MDS, followed by binding free energy analysis. Through screening, 1000 natural product compounds were obtained with docking energy ranging from −8.5 to −4.1 kcal/mol. The top four lead compounds were then selected for further investigation. On comparative analysis of intermolecular interaction, dynamics simulation and MM/GBSA calculation revealed that M3 docked with the DosR protein (docking score = −8.1 kcal/mol, RMSD = ~7 Å and ΔG Bind = −53.51 kcal/mol) exhibited stronger stability than reference compound Ursolic acid (docking score = −6.2 kcal/mol, RMSD = ~13.5 Å and ΔG Bind = −44.51 kcal/mol). Hence, M3 is recommended for further validation through in vitro and in vivo studies against latent tuberculosis infection.

]]> Harnessing Natural Product Compounds to Target Dormancy Survival Regulator (DosR) in Latent Tuberculosis Infection (LTBI): An In Silico Strategy Against Dormancy Mandeep Chouhan Mukesh Kumar Vivek Dhar Dwivedi Vivek Kumar Kashyap Himanshu Narayan Singh Sanjay Kumar doi: 10.3390/arm93030019 Advances in Respiratory Medicine 2025-06-16 Advances in Respiratory Medicine 2025-06-16 93 3 Article 19 10.3390/arm93030019 https://www.mdpi.com/2543-6031/93/3/19 ARM, Vol. 93, Pages 18: Medication Recommendation, Counseling, and Pricing for Nasal Sprays in German Community Pharmacies: A Simulated Patient Investigation https://www.mdpi.com/2543-6031/93/3/18 For the self-medication of nasal congestion following a common cold, decongestant nasal sprays can be recommended according to the medicine guidelines. In Germany, these are only available in community pharmacies (CPs) with free pricing. The aim was to analyze the medication recommendation, counseling, and pricing. A covert simulated patient study, internationally recognized as the “gold standard”, was conducted in all CPs of two medium-sized cities in north-eastern Germany. Each CP was visited twice (86 visits) with the identical scenario by one female and one male simulated patient. At the beginning, they asked for a nasal spray and, when asked, stated that they had had nasal congestion for three days. Slightly more than half (54.7%, 47/86) of the recommended nasal sprays were free of preservatives. The median counseling score was 2.0 out of 8 points, with a significantly higher score observed for the female SP (p = 0.004). Information on the maximum intake duration of five days recommended in the German pharmacy guideline was not provided during any visits. The prices varied in total from EUR 1.95 to EUR 6.22. Therefore, measures by the legislator and the chambers of pharmacists are necessary to sustainably improve the medication recommendation, the counseling, and the price transparency. 2025-06-13 ARM, Vol. 93, Pages 18: Medication Recommendation, Counseling, and Pricing for Nasal Sprays in German Community Pharmacies: A Simulated Patient Investigation

Advances in Respiratory Medicine doi: 10.3390/arm93030018

Authors: Bernhard Langer Christian Kunow Tim Dethloff Sarah George

For the self-medication of nasal congestion following a common cold, decongestant nasal sprays can be recommended according to the medicine guidelines. In Germany, these are only available in community pharmacies (CPs) with free pricing. The aim was to analyze the medication recommendation, counseling, and pricing. A covert simulated patient study, internationally recognized as the “gold standard”, was conducted in all CPs of two medium-sized cities in north-eastern Germany. Each CP was visited twice (86 visits) with the identical scenario by one female and one male simulated patient. At the beginning, they asked for a nasal spray and, when asked, stated that they had had nasal congestion for three days. Slightly more than half (54.7%, 47/86) of the recommended nasal sprays were free of preservatives. The median counseling score was 2.0 out of 8 points, with a significantly higher score observed for the female SP (p = 0.004). Information on the maximum intake duration of five days recommended in the German pharmacy guideline was not provided during any visits. The prices varied in total from EUR 1.95 to EUR 6.22. Therefore, measures by the legislator and the chambers of pharmacists are necessary to sustainably improve the medication recommendation, the counseling, and the price transparency.

]]> Medication Recommendation, Counseling, and Pricing for Nasal Sprays in German Community Pharmacies: A Simulated Patient Investigation Bernhard Langer Christian Kunow Tim Dethloff Sarah George doi: 10.3390/arm93030018 Advances in Respiratory Medicine 2025-06-13 Advances in Respiratory Medicine 2025-06-13 93 3 Article 18 10.3390/arm93030018 https://www.mdpi.com/2543-6031/93/3/18 ARM, Vol. 93, Pages 17: Clinical Utility of ctDNA Analysis in Lung Cancer—A Review https://www.mdpi.com/2543-6031/93/3/17 Circulating free DNA (cfDNA) is genetic material released from various cells into bodily fluids. Among its fractions, circulating tumor DNA (ctDNA) originates from tumor cells and reflects their genetic material, including mutations and epigenetic changes. Methods commonly employed for detecting ctDNA in blood include next-generation sequencing (NGS) and various types of PCR. The presence of ctDNA can be utilized in liquid biopsies for many diagnostic purposes related to various cancers. It is a minimally invasive method of sampling molecular compounds from tumor cells. In this paper, we focus on current knowledge regarding the liquid biopsy of blood ctDNA in the context of lung cancer, one of the leading causes of cancer-related mortality. Currently, as a clinically approved method, liquid biopsy serves as a complementary technique in NSCLC diagnostic and genetic profiling. Other applications of liquid biopsy that are still being investigated include the detection of minimal residual disease (MRD) after curative treatment and response monitoring to systemic treatment. This review discusses current and future potential directions for the development and implementation of ctDNA for patients with NSCLC. 2025-06-12 ARM, Vol. 93, Pages 17: Clinical Utility of ctDNA Analysis in Lung Cancer—A Review

Advances in Respiratory Medicine doi: 10.3390/arm93030017

Authors: Kamil Makar Agata Wróbel Adam Antczak Damian Tworek

Circulating free DNA (cfDNA) is genetic material released from various cells into bodily fluids. Among its fractions, circulating tumor DNA (ctDNA) originates from tumor cells and reflects their genetic material, including mutations and epigenetic changes. Methods commonly employed for detecting ctDNA in blood include next-generation sequencing (NGS) and various types of PCR. The presence of ctDNA can be utilized in liquid biopsies for many diagnostic purposes related to various cancers. It is a minimally invasive method of sampling molecular compounds from tumor cells. In this paper, we focus on current knowledge regarding the liquid biopsy of blood ctDNA in the context of lung cancer, one of the leading causes of cancer-related mortality. Currently, as a clinically approved method, liquid biopsy serves as a complementary technique in NSCLC diagnostic and genetic profiling. Other applications of liquid biopsy that are still being investigated include the detection of minimal residual disease (MRD) after curative treatment and response monitoring to systemic treatment. This review discusses current and future potential directions for the development and implementation of ctDNA for patients with NSCLC.

]]> Clinical Utility of ctDNA Analysis in Lung Cancer—A Review Kamil Makar Agata Wróbel Adam Antczak Damian Tworek doi: 10.3390/arm93030017 Advances in Respiratory Medicine 2025-06-12 Advances in Respiratory Medicine 2025-06-12 93 3 Review 17 10.3390/arm93030017 https://www.mdpi.com/2543-6031/93/3/17 ARM, Vol. 93, Pages 16: Reply to Shafaei B. Comment on “Giraldo-Ocampo et al. B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia. Adv. Respir. Med. 2022, 90, 254–266” https://www.mdpi.com/2543-6031/93/3/16 I am writing in response to the thoughtful observations [...] 2025-06-09 ARM, Vol. 93, Pages 16: Reply to Shafaei B. Comment on “Giraldo-Ocampo et al. B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia. Adv. Respir. Med. 2022, 90, 254–266”

Advances in Respiratory Medicine doi: 10.3390/arm93030016

Authors: Andres F. Zea-Vera

I am writing in response to the thoughtful observations [...]

]]> Reply to Shafaei B. Comment on “Giraldo-Ocampo et al. B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia. Adv. Respir. Med. 2022, 90, 254–266” Andres F. Zea-Vera doi: 10.3390/arm93030016 Advances in Respiratory Medicine 2025-06-09 Advances in Respiratory Medicine 2025-06-09 93 3 Reply 16 10.3390/arm93030016 https://www.mdpi.com/2543-6031/93/3/16 ARM, Vol. 93, Pages 15: Comment on Giraldo-Ocampo et al. B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia. Adv. Respir. Med. 2022, 90, 254–266 https://www.mdpi.com/2543-6031/93/3/15 I am writing regarding the article titled “B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia” [...] 2025-06-09 ARM, Vol. 93, Pages 15: Comment on Giraldo-Ocampo et al. B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia. Adv. Respir. Med. 2022, 90, 254–266

Advances in Respiratory Medicine doi: 10.3390/arm93030015

Authors: Behnam Shafaei

I am writing regarding the article titled “B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia” [...]

]]> Comment on Giraldo-Ocampo et al. B Cell Subsets in Colombian Adults with Predominantly Antibody Deficiencies, Bronchiectasis or Recurrent Pneumonia. Adv. Respir. Med. 2022, 90, 254–266 Behnam Shafaei doi: 10.3390/arm93030015 Advances in Respiratory Medicine 2025-06-09 Advances in Respiratory Medicine 2025-06-09 93 3 Comment 15 10.3390/arm93030015 https://www.mdpi.com/2543-6031/93/3/15 ARM, Vol. 93, Pages 14: Environmental Factors Affecting Sleep Quality in Intensive Care Unit Patients in Southern Morocco: An Assessment Study https://www.mdpi.com/2543-6031/93/3/14 Introduction: Sleep disturbances are a common and often underestimated complication during intensive care unit (ICU) stays. These disturbances can significantly impact patients’ recovery and overall well-being. This study aimed to assess the sleep quality of ICU patients and investigate the environmental and clinical factors that affect sleep quality during their ICU stay. Methods: We conducted a six-month cross-sectional study involving patients who had stayed in the ICU for at least three nights and were oriented to time and place upon discharge. Sleep quality was assessed using the Arabic version of the Freedman Sleep Questionnaire. Both environmental factors (e.g., noise, light, and nursing interventions) and clinical variables (illness severity and pain) were examined. The differences across three time periods were analyzed using the Wilcoxon test and Spearman’s correlation. Multiple regression analysis identified the factors influencing sleep quality. Statistical analyses were performed using JAMOVI software (version 2.3.28). Results: The study enrolled 328 patients, with an average age of 49.74 ± 17.89 years. Of the participants, 75.3% were adults. The primary reasons for admission were circulatory distress (45.73%) and metabolic disorders (24.09%). Sleep quality was significantly lower in the ICU compared to patients’ sleep at home (Z = −14.870, p < 0.001). The EVA and APACHE II scores had a statistically significant effect on sleep quality (p < 0.001 and p = 0.015, respectively). In contrast, the Charlson and Quick SOFA scores did not show significant effects (p = 0.128 and p = 0.894). Environmental factors, including noise (p = 0.008), light (p = 0.009), and nursing interventions (p = 0.009), significantly impacted sleep quality. Conclusions: Patients in the ICU generally reported poor sleep quality. Our findings suggest that improving pain management, minimizing environmental noise, and reducing staff-related disturbances could significantly enhance sleep quality for patients in the intensive care unit (ICU). 2025-06-06 ARM, Vol. 93, Pages 14: Environmental Factors Affecting Sleep Quality in Intensive Care Unit Patients in Southern Morocco: An Assessment Study

Advances in Respiratory Medicine doi: 10.3390/arm93030014

Authors: Abdelmajid Lkoul Keltouma Oumbarek Youssef Bouchriti Asmaa Jniene Tarek Dendane

Introduction: Sleep disturbances are a common and often underestimated complication during intensive care unit (ICU) stays. These disturbances can significantly impact patients’ recovery and overall well-being. This study aimed to assess the sleep quality of ICU patients and investigate the environmental and clinical factors that affect sleep quality during their ICU stay. Methods: We conducted a six-month cross-sectional study involving patients who had stayed in the ICU for at least three nights and were oriented to time and place upon discharge. Sleep quality was assessed using the Arabic version of the Freedman Sleep Questionnaire. Both environmental factors (e.g., noise, light, and nursing interventions) and clinical variables (illness severity and pain) were examined. The differences across three time periods were analyzed using the Wilcoxon test and Spearman’s correlation. Multiple regression analysis identified the factors influencing sleep quality. Statistical analyses were performed using JAMOVI software (version 2.3.28). Results: The study enrolled 328 patients, with an average age of 49.74 ± 17.89 years. Of the participants, 75.3% were adults. The primary reasons for admission were circulatory distress (45.73%) and metabolic disorders (24.09%). Sleep quality was significantly lower in the ICU compared to patients’ sleep at home (Z = −14.870, p < 0.001). The EVA and APACHE II scores had a statistically significant effect on sleep quality (p < 0.001 and p = 0.015, respectively). In contrast, the Charlson and Quick SOFA scores did not show significant effects (p = 0.128 and p = 0.894). Environmental factors, including noise (p = 0.008), light (p = 0.009), and nursing interventions (p = 0.009), significantly impacted sleep quality. Conclusions: Patients in the ICU generally reported poor sleep quality. Our findings suggest that improving pain management, minimizing environmental noise, and reducing staff-related disturbances could significantly enhance sleep quality for patients in the intensive care unit (ICU).

]]> Environmental Factors Affecting Sleep Quality in Intensive Care Unit Patients in Southern Morocco: An Assessment Study Abdelmajid Lkoul Keltouma Oumbarek Youssef Bouchriti Asmaa Jniene Tarek Dendane doi: 10.3390/arm93030014 Advances in Respiratory Medicine 2025-06-06 Advances in Respiratory Medicine 2025-06-06 93 3 Article 14 10.3390/arm93030014 https://www.mdpi.com/2543-6031/93/3/14 ARM, Vol. 93, Pages 13: Efficacy and Safety of P. hybridus Leaf Extract Ze 339 for the Treatment of Allergic Rhinitis https://www.mdpi.com/2543-6031/93/3/13 Allergic rhinitis (AR) is a global health problem on the rise. More and more people are affected, and climate change is exacerbating this health problem in the long term. The quality of life of those affected is often severely compromised, and the financial burden on healthcare systems cannot be disregarded. Therefore, effective and safe medicines are needed to counteract this trend. P. hybridus (butterbur) leaf extract (Ze 339) displays a promising alternative to antihistamines in the treatment of AR symptoms. More than two decades after the first market launch it is now possible to draw a meaningful conclusion on its safety and efficacy. This review summarizes the available preclinical and clinical data, real-world data (RWD) as well as data from post-marketing pharmacovigilance monitoring about the herbal medicinal drug Ze 339. It focusses on the current knowledge about the mode of action as well as the evaluation of its efficacy and safety in the treatment of AR. Given its favourable safety profile and lack of sedative side effects, Ze 339 offers a valuable alternative to antihistamines and should therefore continue to be considered by medical practitioners for the treatment of allergic rhinitis symptoms. 2025-06-03 ARM, Vol. 93, Pages 13: Efficacy and Safety of P. hybridus Leaf Extract Ze 339 for the Treatment of Allergic Rhinitis

Advances in Respiratory Medicine doi: 10.3390/arm93030013

Authors: Verena M. Merk Georg Boonen Veronika Butterweck Andreas Schapowal

Allergic rhinitis (AR) is a global health problem on the rise. More and more people are affected, and climate change is exacerbating this health problem in the long term. The quality of life of those affected is often severely compromised, and the financial burden on healthcare systems cannot be disregarded. Therefore, effective and safe medicines are needed to counteract this trend. P. hybridus (butterbur) leaf extract (Ze 339) displays a promising alternative to antihistamines in the treatment of AR symptoms. More than two decades after the first market launch it is now possible to draw a meaningful conclusion on its safety and efficacy. This review summarizes the available preclinical and clinical data, real-world data (RWD) as well as data from post-marketing pharmacovigilance monitoring about the herbal medicinal drug Ze 339. It focusses on the current knowledge about the mode of action as well as the evaluation of its efficacy and safety in the treatment of AR. Given its favourable safety profile and lack of sedative side effects, Ze 339 offers a valuable alternative to antihistamines and should therefore continue to be considered by medical practitioners for the treatment of allergic rhinitis symptoms.

]]> Efficacy and Safety of P. hybridus Leaf Extract Ze 339 for the Treatment of Allergic Rhinitis Verena M. Merk Georg Boonen Veronika Butterweck Andreas Schapowal doi: 10.3390/arm93030013 Advances in Respiratory Medicine 2025-06-03 Advances in Respiratory Medicine 2025-06-03 93 3 Review 13 10.3390/arm93030013 https://www.mdpi.com/2543-6031/93/3/13 ARM, Vol. 93, Pages 12: High Prevalence of Depression and Anxiety in Patients with Chronic Respiratory Diseases Admitted to Intensive Care in a Low-Resource Setting https://www.mdpi.com/2543-6031/93/3/12 Background: Depression and anxiety are common in patients with chronic respiratory diseases (CRDs), but their prevalence in intensive care settings, particularly in low-resource regions, remains underexplored. Objective: To assess the prevalence and severity of depression and anxiety in patients with CRDs admitted to an intensive care unit (ICU) and identify associated factors. Methods: A cross-sectional study was conducted at Gulab Devi Teaching Hospital, Lahore, Pakistan. Adult patients with CRDs admitted to the ICU were assessed using the Hamilton Depression Rating Scale. Statistical analyses included Fisher’s exact test, Mann–Whitney/Kruskal–Wallis tests, and logistic regression. Results: Depression was highly prevalent across all CRD categories: 83%, 89%, 84%, and 93% in obstructive, restrictive, infectious, and other respiratory disease categories, and severe depression in 16%, 18%, 14%, and 37%, respectively. Anxiety symptoms were also widespread (77–100%), with no significant differences across disease groups. Depression was significantly associated with older age (p < 0.001, OR 1.08) and anxiety symptoms (p < 0.001, OR 47.07). Female gender was linked to anxiety (p = 0.034, OR 4.17). Conclusion: The high burden of depression and anxiety in ICU patients with CRDs underscores the need for routine psychiatric screening and integrated mental health care in critical-care settings. 2025-06-02 ARM, Vol. 93, Pages 12: High Prevalence of Depression and Anxiety in Patients with Chronic Respiratory Diseases Admitted to Intensive Care in a Low-Resource Setting

Advances in Respiratory Medicine doi: 10.3390/arm93030012

Authors: Amun Mustafa Asifa Karamat Wajeeha Mustansar Toor Tehmina Mustafa

Background: Depression and anxiety are common in patients with chronic respiratory diseases (CRDs), but their prevalence in intensive care settings, particularly in low-resource regions, remains underexplored. Objective: To assess the prevalence and severity of depression and anxiety in patients with CRDs admitted to an intensive care unit (ICU) and identify associated factors. Methods: A cross-sectional study was conducted at Gulab Devi Teaching Hospital, Lahore, Pakistan. Adult patients with CRDs admitted to the ICU were assessed using the Hamilton Depression Rating Scale. Statistical analyses included Fisher’s exact test, Mann–Whitney/Kruskal–Wallis tests, and logistic regression. Results: Depression was highly prevalent across all CRD categories: 83%, 89%, 84%, and 93% in obstructive, restrictive, infectious, and other respiratory disease categories, and severe depression in 16%, 18%, 14%, and 37%, respectively. Anxiety symptoms were also widespread (77–100%), with no significant differences across disease groups. Depression was significantly associated with older age (p < 0.001, OR 1.08) and anxiety symptoms (p < 0.001, OR 47.07). Female gender was linked to anxiety (p = 0.034, OR 4.17). Conclusion: The high burden of depression and anxiety in ICU patients with CRDs underscores the need for routine psychiatric screening and integrated mental health care in critical-care settings.

]]> High Prevalence of Depression and Anxiety in Patients with Chronic Respiratory Diseases Admitted to Intensive Care in a Low-Resource Setting Amun Mustafa Asifa Karamat Wajeeha Mustansar Toor Tehmina Mustafa doi: 10.3390/arm93030012 Advances in Respiratory Medicine 2025-06-02 Advances in Respiratory Medicine 2025-06-02 93 3 Article 12 10.3390/arm93030012 https://www.mdpi.com/2543-6031/93/3/12 ARM, Vol. 93, Pages 11: Malnutrition, Sarcopenia, and Malnutrition Sarcopenia Syndrome in Idiopathic Pulmonary Fibrosis https://www.mdpi.com/2543-6031/93/3/11 Introduction: Idiopathic pulmonaryy fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. While comorbidities like pulmonary hypertension and lung cancer have been studied extensively, less attention has been paid to the implications of malnutrition and sarcopenia in patients with IPF. This study aimed to assess the prevalence of malnutrition, sarcopenia, and the combined malnutrition-sarcopenia syndrome in patients with IPF using the latest diagnostic criteria from the Global Leadership Initiative on Malnutrition (GLIM) and the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Methods: A prospective, observational, multicenter study was conducted, focusing on patients with idiopathic pulmonary fibrosis (IPF). All participants provided informed consent, and the study followed ethical guidelines. Malnutrition was diagnosed based on the GLIM criteria, requiring one phenotypic and one etiological criterion, with muscle mass assessed via bioelectrical impedance analysis (BIA). Sarcopenia was screened following the EWGSOP2 recommendations. The statistical analysis was performed using JAMOVI version 2.3.22, with significance set at p < 0.05. Results: The findings revealed that 77.65% of the participants were malnourished, and 20% had sarcopenia. The malnourished patients had significantly lower body weight, height, and muscle mass compared to the non-malnourished patients. Furthermore, the patients with malnutrition exhibited poorer health-related quality of life scores. This study also identified the malnutrition-sarcopenia syndrome in 8.23% of the participants. Conclusions: Malnutrition, based on the GLIM criteria was identified in three out of four patients with IPF, while sarcopenia according to the EWGSOP2 was present in one out of five. This study underscores the necessity for routine screening for malnutrition and sarcopenia in patients with IPF. 2025-05-29 ARM, Vol. 93, Pages 11: Malnutrition, Sarcopenia, and Malnutrition Sarcopenia Syndrome in Idiopathic Pulmonary Fibrosis

Advances in Respiratory Medicine doi: 10.3390/arm93030011

Authors: Eva Cabrera-César Rocío Fernández-Jiménez Javier Lopez-Garcia Alicia Sanmartín-Sánchez Miguel Benítez Cano-Gamonoso Isabel Asschert Agüero Francisco Espíldora-Hernández Luis Fernandez de Rota Garcia Isabel Vega-Aguilar Maria del Mar Amaya-Campos Francisco J. Tinahones Jose Manuel Garcia-Almeida Jose Luis Velasco-Garrido

Introduction: Idiopathic pulmonaryy fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. While comorbidities like pulmonary hypertension and lung cancer have been studied extensively, less attention has been paid to the implications of malnutrition and sarcopenia in patients with IPF. This study aimed to assess the prevalence of malnutrition, sarcopenia, and the combined malnutrition-sarcopenia syndrome in patients with IPF using the latest diagnostic criteria from the Global Leadership Initiative on Malnutrition (GLIM) and the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Methods: A prospective, observational, multicenter study was conducted, focusing on patients with idiopathic pulmonary fibrosis (IPF). All participants provided informed consent, and the study followed ethical guidelines. Malnutrition was diagnosed based on the GLIM criteria, requiring one phenotypic and one etiological criterion, with muscle mass assessed via bioelectrical impedance analysis (BIA). Sarcopenia was screened following the EWGSOP2 recommendations. The statistical analysis was performed using JAMOVI version 2.3.22, with significance set at p < 0.05. Results: The findings revealed that 77.65% of the participants were malnourished, and 20% had sarcopenia. The malnourished patients had significantly lower body weight, height, and muscle mass compared to the non-malnourished patients. Furthermore, the patients with malnutrition exhibited poorer health-related quality of life scores. This study also identified the malnutrition-sarcopenia syndrome in 8.23% of the participants. Conclusions: Malnutrition, based on the GLIM criteria was identified in three out of four patients with IPF, while sarcopenia according to the EWGSOP2 was present in one out of five. This study underscores the necessity for routine screening for malnutrition and sarcopenia in patients with IPF.

]]> Malnutrition, Sarcopenia, and Malnutrition Sarcopenia Syndrome in Idiopathic Pulmonary Fibrosis Eva Cabrera-César Rocío Fernández-Jiménez Javier Lopez-Garcia Alicia Sanmartín-Sánchez Miguel Benítez Cano-Gamonoso Isabel Asschert Agüero Francisco Espíldora-Hernández Luis Fernandez de Rota Garcia Isabel Vega-Aguilar Maria del Mar Amaya-Campos Francisco J. Tinahones Jose Manuel Garcia-Almeida Jose Luis Velasco-Garrido doi: 10.3390/arm93030011 Advances in Respiratory Medicine 2025-05-29 Advances in Respiratory Medicine 2025-05-29 93 3 Article 11 10.3390/arm93030011 https://www.mdpi.com/2543-6031/93/3/11 ARM, Vol. 93, Pages 10: Inspiratory Muscle Training Improved Cardiorespiratory Performance in Patients Undergoing Open Heart Surgery: A Randomized Controlled Trial https://www.mdpi.com/2543-6031/93/3/10 Aim: This study aimed to evaluate the effects of inspiratory muscle training on inspiratory muscle strength and cardiorespiratory performance in patients undergoing open heart surgery. Method: This study was conducted as a randomized controlled trial with two groups. Fifty-eight patients who underwent open heart surgery were randomly assigned to either the intervention group or the control group 29 in the control group and 29 in the intervention group. Patients in the intervention group participated in a physical therapy program combined with inspiratory muscle training using the Thammasat University (TU) Breath Trainer. Patients in the control group received only the standard physical therapy program. The maximum inspiratory pressure, maximum expiratory pressure and 6 min walk test distance were assessed both before surgery and prior to hospital discharge. Results: The intervention group had a significant increase in maximum inspiratory pressure (p < 0.001), maximum expiratory pressure (p < 0.001) and 6 min walk test distance (p = 0.013). The control group had a significant decrease in maximum inspiratory pressure (p < 0.001), maximum expiratory pressure (p = 0.002) and 6 min walk test distance (p < 0.001). Conclusions: Inspiratory muscle training can be performed using maximum pressure resistors, such as the TU-Breath Trainer device. This training has been shown to effectively improve inspiratory muscle strength and cardiorespiratory performance in patients undergoing open heart surgery, as well as reduce pulmonary complications and shorten the length of hospital stay. 2025-05-27 ARM, Vol. 93, Pages 10: Inspiratory Muscle Training Improved Cardiorespiratory Performance in Patients Undergoing Open Heart Surgery: A Randomized Controlled Trial

Advances in Respiratory Medicine doi: 10.3390/arm93030010

Authors: Chitima Kulchanarat Suphannee Choeirod Supattra Thadatheerapat Dusarkorn Piathip Opas Satdhabudha Kornanong Yuenyongchaiwat

Aim: This study aimed to evaluate the effects of inspiratory muscle training on inspiratory muscle strength and cardiorespiratory performance in patients undergoing open heart surgery. Method: This study was conducted as a randomized controlled trial with two groups. Fifty-eight patients who underwent open heart surgery were randomly assigned to either the intervention group or the control group 29 in the control group and 29 in the intervention group. Patients in the intervention group participated in a physical therapy program combined with inspiratory muscle training using the Thammasat University (TU) Breath Trainer. Patients in the control group received only the standard physical therapy program. The maximum inspiratory pressure, maximum expiratory pressure and 6 min walk test distance were assessed both before surgery and prior to hospital discharge. Results: The intervention group had a significant increase in maximum inspiratory pressure (p < 0.001), maximum expiratory pressure (p < 0.001) and 6 min walk test distance (p = 0.013). The control group had a significant decrease in maximum inspiratory pressure (p < 0.001), maximum expiratory pressure (p = 0.002) and 6 min walk test distance (p < 0.001). Conclusions: Inspiratory muscle training can be performed using maximum pressure resistors, such as the TU-Breath Trainer device. This training has been shown to effectively improve inspiratory muscle strength and cardiorespiratory performance in patients undergoing open heart surgery, as well as reduce pulmonary complications and shorten the length of hospital stay.

]]> Inspiratory Muscle Training Improved Cardiorespiratory Performance in Patients Undergoing Open Heart Surgery: A Randomized Controlled Trial Chitima Kulchanarat Suphannee Choeirod Supattra Thadatheerapat Dusarkorn Piathip Opas Satdhabudha Kornanong Yuenyongchaiwat doi: 10.3390/arm93030010 Advances in Respiratory Medicine 2025-05-27 Advances in Respiratory Medicine 2025-05-27 93 3 Article 10 10.3390/arm93030010 https://www.mdpi.com/2543-6031/93/3/10 ARM, Vol. 93, Pages 9: Changes in Lung Ultrasound in Systemic Sclerosis Before and After Rehabilitation: A Comparative Study Between People with and Without Interstitial Lung Disease https://www.mdpi.com/2543-6031/93/3/9 There is limited research on the impact of a physiotherapy-guided rehabilitation program (PGRP) on lung structure in systemic sclerosis (SSc). Lung ultrasound (LUS) has been used for over a decade to identify interstitial lung disease associated with SSc (SSc-ILD). This study aims to evaluate the impact of a PGRP on LUS signals in women with SSc-ILD and women without ILD (SSc-wILD). This is a longitudinal quasi-experimental study that included 33 women with SSc. The results show that changes in LUS were observed in 22 participants, especially B-lines > two. Before the PGRP the median of B-lines > two was three (0–7), while after the PGRP it was three (0–6) (p = 0.020). The aeration score was eight (0–16.5) pre-PGRP and three (0–16) post-PGRP (p = 0.013). Analyzing the impact of the PGRP on LUS signals in SSc-ILD and SSc-wILD groups, the main change observed was a reduction in B-lines > two between pre-PGRP and post-PGRP in the SSc-ILD group (p = 0.0004). The SSc-ILD group had a higher aeration score than the SSc-wILD group both pre-PGRP (p < 0.0001) and post-PGRP (p = 0.0001)]. In conclusion, LUS may be a complementary tool for assessing pre- and post-PGRP changes in people with SSc-ILD and SSc-wILD. Our data also suggest that the PGRP can elicit measurable changes in LUS findings in SSc, particularly in SSc-ILD. These findings support the inclusion of LUS in the routine monitoring of SSc and the use of a PGRP as a non-pharmacologic adjunctive strategy in SSc. 2025-05-20 ARM, Vol. 93, Pages 9: Changes in Lung Ultrasound in Systemic Sclerosis Before and After Rehabilitation: A Comparative Study Between People with and Without Interstitial Lung Disease

Advances in Respiratory Medicine doi: 10.3390/arm93030009

Authors: Samantha Gomes de Alegria Matheus Mello da Silva Jéssica Gabriela Messias Oliveira Beatriz Luiza Pinheiro Alves de Azevedo Nathália Alves de Oliveira Saraiva Isabelle da Nóbrega Ferreira Joana Acar Silva Thiago Thomaz Mafort Cláudia Henrique da Costa Agnaldo José Lopes

There is limited research on the impact of a physiotherapy-guided rehabilitation program (PGRP) on lung structure in systemic sclerosis (SSc). Lung ultrasound (LUS) has been used for over a decade to identify interstitial lung disease associated with SSc (SSc-ILD). This study aims to evaluate the impact of a PGRP on LUS signals in women with SSc-ILD and women without ILD (SSc-wILD). This is a longitudinal quasi-experimental study that included 33 women with SSc. The results show that changes in LUS were observed in 22 participants, especially B-lines > two. Before the PGRP the median of B-lines > two was three (0–7), while after the PGRP it was three (0–6) (p = 0.020). The aeration score was eight (0–16.5) pre-PGRP and three (0–16) post-PGRP (p = 0.013). Analyzing the impact of the PGRP on LUS signals in SSc-ILD and SSc-wILD groups, the main change observed was a reduction in B-lines > two between pre-PGRP and post-PGRP in the SSc-ILD group (p = 0.0004). The SSc-ILD group had a higher aeration score than the SSc-wILD group both pre-PGRP (p < 0.0001) and post-PGRP (p = 0.0001)]. In conclusion, LUS may be a complementary tool for assessing pre- and post-PGRP changes in people with SSc-ILD and SSc-wILD. Our data also suggest that the PGRP can elicit measurable changes in LUS findings in SSc, particularly in SSc-ILD. These findings support the inclusion of LUS in the routine monitoring of SSc and the use of a PGRP as a non-pharmacologic adjunctive strategy in SSc.

]]> Changes in Lung Ultrasound in Systemic Sclerosis Before and After Rehabilitation: A Comparative Study Between People with and Without Interstitial Lung Disease Samantha Gomes de Alegria Matheus Mello da Silva Jéssica Gabriela Messias Oliveira Beatriz Luiza Pinheiro Alves de Azevedo Nathália Alves de Oliveira Saraiva Isabelle da Nóbrega Ferreira Joana Acar Silva Thiago Thomaz Mafort Cláudia Henrique da Costa Agnaldo José Lopes doi: 10.3390/arm93030009 Advances in Respiratory Medicine 2025-05-20 Advances in Respiratory Medicine 2025-05-20 93 3 Article 9 10.3390/arm93030009 https://www.mdpi.com/2543-6031/93/3/9 ARM, Vol. 93, Pages 8: Mobile Phone-Mediated Interventions to Improve Adherence to Prescribed Treatment in Chronic Obstructive Pulmonary Disease: A Systematic Review https://www.mdpi.com/2543-6031/93/2/8 Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder that poses significant challenges in treatment adherence. This systematic review evaluates the effectiveness of mobile health (mHealth) interventions compared to conventional therapy in improving treatment adherence among COPD patients. A total of 13 randomized controlled trials and comparative cohort studies published up to July 2023 were included, analyzing interventions such as medication reminders and remote monitoring in adult COPD patients. Studies involving participants under 18 years of age or with severe comorbidities were excluded. This review identified 4688 records from MEDLINE, WEB OF SCIENCE, and SCOPUS. Of these, 13 studies met the inclusion criteria. The selection process was conducted by two independent reviewers, with discrepancies resolved by consensus with a third reviewer. The results showed that mHealth interventions improved treatment adherence in some studies, particularly in exercise and symptom monitoring; however, the evidence was inconsistent, and results varied across studies. This review concludes that mHealth interventions have the potential to improve adherence but higher-quality studies and more robust designs are needed to confirm these findings and support their clinical implementation. 2025-04-18 ARM, Vol. 93, Pages 8: Mobile Phone-Mediated Interventions to Improve Adherence to Prescribed Treatment in Chronic Obstructive Pulmonary Disease: A Systematic Review

Advances in Respiratory Medicine doi: 10.3390/arm93020008

Authors: Andrea Paleo Catalina Carretta Francisca Pinto Estefanno Saltori Joaquín González Aroca Álvaro Puelles

Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder that poses significant challenges in treatment adherence. This systematic review evaluates the effectiveness of mobile health (mHealth) interventions compared to conventional therapy in improving treatment adherence among COPD patients. A total of 13 randomized controlled trials and comparative cohort studies published up to July 2023 were included, analyzing interventions such as medication reminders and remote monitoring in adult COPD patients. Studies involving participants under 18 years of age or with severe comorbidities were excluded. This review identified 4688 records from MEDLINE, WEB OF SCIENCE, and SCOPUS. Of these, 13 studies met the inclusion criteria. The selection process was conducted by two independent reviewers, with discrepancies resolved by consensus with a third reviewer. The results showed that mHealth interventions improved treatment adherence in some studies, particularly in exercise and symptom monitoring; however, the evidence was inconsistent, and results varied across studies. This review concludes that mHealth interventions have the potential to improve adherence but higher-quality studies and more robust designs are needed to confirm these findings and support their clinical implementation.

]]> Mobile Phone-Mediated Interventions to Improve Adherence to Prescribed Treatment in Chronic Obstructive Pulmonary Disease: A Systematic Review Andrea Paleo Catalina Carretta Francisca Pinto Estefanno Saltori Joaquín González Aroca Álvaro Puelles doi: 10.3390/arm93020008 Advances in Respiratory Medicine 2025-04-18 Advances in Respiratory Medicine 2025-04-18 93 2 Review 8 10.3390/arm93020008 https://www.mdpi.com/2543-6031/93/2/8 ARM, Vol. 93, Pages 7: Heterozygous Men1(+/T) Knockout Mice Do Not Develop Bronchopulmonary Neuroendocrine Hyperplasia or Neoplasia but Bronchial Adenocarcinoma https://www.mdpi.com/2543-6031/93/2/7 Introduction: Bronchopulmonary Neuroendocrine Neoplasms (NEN) occur in 2–7% of patients with multiple endocrine neoplasia type 1 (MEN1). Precursor lesions have been identified for MEN1-related pancreatic, duodenal, and gastric NEN. The aim of the current study using a MEN1 mouse model was to define the precursor lesions of bronchopulmonary NEN and evaluate the potential prophylactic antitumor effects of somatostatin analogues in a transgenic MEN1 mouse model. Methods: Fifteen mice, germline heterozygous for Men1(+/T), were treated with subcutaneous injections of lanreotide autogel (Somatuline Autogel®, IPSEN Pharma), while 15 mice were treated with subcutaneous injections of physiologic sodium chloride as the control group. Five mice from each group were euthanized after 12, 15, and 18 months, respectively. The complete lungs were resected and evaluated after hematoxylin and eosin staining and immunohistochemistry for synaptophysin and chromogranin A. Results: In the lungs of the 30 evaluated mice, whether treated or placebo treated, no bronchopulmonary neuroendocrine cell hyperplasia nor neuroendocrine neoplasia was detected through histopathology. However, pulmonary adenocarcinoma developed in 2 (13%) of the 15 untreated mice and in 1 (7%) of the 15 lanreotide-treated mice. Conclusions: Heterozygous Men1(+/T) knockout mice do not develop bronchopulmonary NEN or precursor lesions, but pulmonary adenocarcinoma. This surprising result needs to be investigated in more detail. 2025-03-31 ARM, Vol. 93, Pages 7: Heterozygous Men1(+/T) Knockout Mice Do Not Develop Bronchopulmonary Neuroendocrine Hyperplasia or Neoplasia but Bronchial Adenocarcinoma

Advances in Respiratory Medicine doi: 10.3390/arm93020007

Authors: Max B. Albers Ludger Fink Jerena Manoharan Caroline L. Lopez Carmen Bollmann Detlef K. Bartsch

Introduction: Bronchopulmonary Neuroendocrine Neoplasms (NEN) occur in 2–7% of patients with multiple endocrine neoplasia type 1 (MEN1). Precursor lesions have been identified for MEN1-related pancreatic, duodenal, and gastric NEN. The aim of the current study using a MEN1 mouse model was to define the precursor lesions of bronchopulmonary NEN and evaluate the potential prophylactic antitumor effects of somatostatin analogues in a transgenic MEN1 mouse model. Methods: Fifteen mice, germline heterozygous for Men1(+/T), were treated with subcutaneous injections of lanreotide autogel (Somatuline Autogel®, IPSEN Pharma), while 15 mice were treated with subcutaneous injections of physiologic sodium chloride as the control group. Five mice from each group were euthanized after 12, 15, and 18 months, respectively. The complete lungs were resected and evaluated after hematoxylin and eosin staining and immunohistochemistry for synaptophysin and chromogranin A. Results: In the lungs of the 30 evaluated mice, whether treated or placebo treated, no bronchopulmonary neuroendocrine cell hyperplasia nor neuroendocrine neoplasia was detected through histopathology. However, pulmonary adenocarcinoma developed in 2 (13%) of the 15 untreated mice and in 1 (7%) of the 15 lanreotide-treated mice. Conclusions: Heterozygous Men1(+/T) knockout mice do not develop bronchopulmonary NEN or precursor lesions, but pulmonary adenocarcinoma. This surprising result needs to be investigated in more detail.

]]> Heterozygous Men1(+/T) Knockout Mice Do Not Develop Bronchopulmonary Neuroendocrine Hyperplasia or Neoplasia but Bronchial Adenocarcinoma Max B. Albers Ludger Fink Jerena Manoharan Caroline L. Lopez Carmen Bollmann Detlef K. Bartsch doi: 10.3390/arm93020007 Advances in Respiratory Medicine 2025-03-31 Advances in Respiratory Medicine 2025-03-31 93 2 Article 7 10.3390/arm93020007 https://www.mdpi.com/2543-6031/93/2/7 ARM, Vol. 93, Pages 6: The Impact of Corticosteroids on Mortality in Acute Exacerbations of Idiopathic Pulmonary Fibrosis: A Meta-Analysis https://www.mdpi.com/2543-6031/93/2/6 Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is one of the most challenging events in the disease course due to the high mortality despite treatment. The role of corticosteroid treatment in AE-IPF has never been defined, even though it is used in current clinical practice. We performed a meta-analysis to determine the effects of steroid treatment on the acute exacerbation outcomes in idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate the impact of steroids on mortality in patients affected by an acute exacerbation of IPF. Methods: This meta-analysis was performed in accordance with the PRISMA statement. A systemic literature search was conducted through Google Scholar, Scopus, WoS, PubMed, and JSTOR. Manuscripts from January 2014 to September 2024 were included in the analysis. Articles were included on whether participants had an acute exacerbation of IPF. Regarding the intervention performed, we evaluated the studies in which patients underwent treatment with corticosteroids. As outcomes, studies were included if they analyzed the overall mortality. Results: A total of 2156 records were initially identified. Nineteen studies (3277 patients) were ultimately included in the final analysis, comparing 1552 patients who received steroids to 1725 patients without steroids. Steroid treatment poses a higher risk, as suggested by the summary measures (RR of 1.78; CI 1.29–2.76, p = 0.00001). Conclusions: This meta-analysis investigated the debated role of corticosteroid treatment during acute exacerbation of idiopathic pulmonary fibrosis. Overall, steroid therapy is associated with increased risk. Clinicians should carefully weigh the risks and benefits of corticosteroid therapy in acute exacerbation of IPF. 2025-03-28 ARM, Vol. 93, Pages 6: The Impact of Corticosteroids on Mortality in Acute Exacerbations of Idiopathic Pulmonary Fibrosis: A Meta-Analysis

Advances in Respiratory Medicine doi: 10.3390/arm93020006

Authors: Pier-Valerio Mari Angelo Coppola Lorenzo Carriera Francesco Macagno

Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is one of the most challenging events in the disease course due to the high mortality despite treatment. The role of corticosteroid treatment in AE-IPF has never been defined, even though it is used in current clinical practice. We performed a meta-analysis to determine the effects of steroid treatment on the acute exacerbation outcomes in idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate the impact of steroids on mortality in patients affected by an acute exacerbation of IPF. Methods: This meta-analysis was performed in accordance with the PRISMA statement. A systemic literature search was conducted through Google Scholar, Scopus, WoS, PubMed, and JSTOR. Manuscripts from January 2014 to September 2024 were included in the analysis. Articles were included on whether participants had an acute exacerbation of IPF. Regarding the intervention performed, we evaluated the studies in which patients underwent treatment with corticosteroids. As outcomes, studies were included if they analyzed the overall mortality. Results: A total of 2156 records were initially identified. Nineteen studies (3277 patients) were ultimately included in the final analysis, comparing 1552 patients who received steroids to 1725 patients without steroids. Steroid treatment poses a higher risk, as suggested by the summary measures (RR of 1.78; CI 1.29–2.76, p = 0.00001). Conclusions: This meta-analysis investigated the debated role of corticosteroid treatment during acute exacerbation of idiopathic pulmonary fibrosis. Overall, steroid therapy is associated with increased risk. Clinicians should carefully weigh the risks and benefits of corticosteroid therapy in acute exacerbation of IPF.

]]> The Impact of Corticosteroids on Mortality in Acute Exacerbations of Idiopathic Pulmonary Fibrosis: A Meta-Analysis Pier-Valerio Mari Angelo Coppola Lorenzo Carriera Francesco Macagno doi: 10.3390/arm93020006 Advances in Respiratory Medicine 2025-03-28 Advances in Respiratory Medicine 2025-03-28 93 2 Article 6 10.3390/arm93020006 https://www.mdpi.com/2543-6031/93/2/6 ARM, Vol. 93, Pages 5: Are There Differences in Postural Control and Muscular Activity in Individuals with COPD and with and Without Sarcopenia? https://www.mdpi.com/2543-6031/93/1/5 Aim: The aim of this study was to compare balance performance and electromyographic activity in individuals with COPD, with and without sarcopenia. Method: Thirty-five patients with COPD were classified with and without sarcopenia according to EWGSOP criteria. Balance was assessed using a force platform under four conditions: standing with feet apart and eyes opened (FHEO), eyes closed (FHEC), on an unstable surface (US), and on one leg (OLS). The surface electromyography activity of lower limb muscles and trunks was recorded. Additionally, the timed up and go test (TUG) and the Brief Balance Evaluation Systems Test (Brief-BESTest) were also utilized. Results: Under the FHEO, FHEC, and US conditions, individuals with sarcopenia demonstrated increased velocities, larger oscillation amplitudes, and greater center of pressure displacements under the US condition (p ≤ 0.02). They also showed a higher activation of the scalene, sternocleidomastoid, and abdominal muscles during OLS, along with a reduced activation of the tibialis anterior during OLS and US, and a decreased activation of the vastus medialis during FHEC and US (p ≤ 0.04). Furthermore, sarcopenic COPD patients exhibited poorer performance on the TUG and Brief-BESTest compared to their non-sarcopenic counterparts (p ≤ 0.02). Conclusions: Individuals with COPD and sarcopenia demonstrated greater instability in both bipedal stances and on unstable surfaces, as well as poorer performance in both dynamic and static balance assessments. Furthermore, these individuals exhibited reduced muscular activation in the lower limbs compared to those without sarcopenia. 2025-02-18 ARM, Vol. 93, Pages 5: Are There Differences in Postural Control and Muscular Activity in Individuals with COPD and with and Without Sarcopenia?

Advances in Respiratory Medicine doi: 10.3390/arm93010005

Authors: Walter Sepúlveda-Loyola Alejandro Álvarez-Bustos Juan José Valenzuela-Fuenzalida Carla María Ordinola Ramírez Carol Saldías Solis Vanessa Suziane Probst

Aim: The aim of this study was to compare balance performance and electromyographic activity in individuals with COPD, with and without sarcopenia. Method: Thirty-five patients with COPD were classified with and without sarcopenia according to EWGSOP criteria. Balance was assessed using a force platform under four conditions: standing with feet apart and eyes opened (FHEO), eyes closed (FHEC), on an unstable surface (US), and on one leg (OLS). The surface electromyography activity of lower limb muscles and trunks was recorded. Additionally, the timed up and go test (TUG) and the Brief Balance Evaluation Systems Test (Brief-BESTest) were also utilized. Results: Under the FHEO, FHEC, and US conditions, individuals with sarcopenia demonstrated increased velocities, larger oscillation amplitudes, and greater center of pressure displacements under the US condition (p ≤ 0.02). They also showed a higher activation of the scalene, sternocleidomastoid, and abdominal muscles during OLS, along with a reduced activation of the tibialis anterior during OLS and US, and a decreased activation of the vastus medialis during FHEC and US (p ≤ 0.04). Furthermore, sarcopenic COPD patients exhibited poorer performance on the TUG and Brief-BESTest compared to their non-sarcopenic counterparts (p ≤ 0.02). Conclusions: Individuals with COPD and sarcopenia demonstrated greater instability in both bipedal stances and on unstable surfaces, as well as poorer performance in both dynamic and static balance assessments. Furthermore, these individuals exhibited reduced muscular activation in the lower limbs compared to those without sarcopenia.

]]> Are There Differences in Postural Control and Muscular Activity in Individuals with COPD and with and Without Sarcopenia? Walter Sepúlveda-Loyola Alejandro Álvarez-Bustos Juan José Valenzuela-Fuenzalida Carla María Ordinola Ramírez Carol Saldías Solis Vanessa Suziane Probst doi: 10.3390/arm93010005 Advances in Respiratory Medicine 2025-02-18 Advances in Respiratory Medicine 2025-02-18 93 1 Article 5 10.3390/arm93010005 https://www.mdpi.com/2543-6031/93/1/5 ARM, Vol. 93, Pages 4: A Meta-Analysis of the Impact of Using Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin II Receptor Blockers (ARBs) on Mortality, Severity, and Healthcare Resource Utilization in Patients with COVID-19 https://www.mdpi.com/2543-6031/93/1/4 Objective: The primary objective of this study is to explore the potential link between the utilization of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and its impact on mortality, disease severity, and healthcare resource utilization in individuals diagnosed with COVID-19. We aim to establish a solid theoretical foundation for safe and effective clinical medications. Methods: We conducted a comprehensive search of various databases, including CNKI, PubMed, Science, Cell, Springer, Nature, Web of Science, and Embase. We also traced the literature of the included studies to ensure a thorough analysis of the available evidence. After applying a set of inclusion and exclusion criteria, we ultimately included a total of 41 articles in our analysis. To determine the overall effect size for dichotomous variables, we used the Mantel–Haenszel odds ratio in random effect models. For continuous variables, we calculated the inverse variance SMD using random effect models. To assess the outcomes and heterogeneity, we considered p-values (p < 0.05) and I2 values for all outcomes. We performed multivariate and univariate meta-regression analyses using the maximum likelihood approach with the CMA 3.0 software. Results: The results of our analysis indicated that the use of ACEIs or ARBs did not significantly influence mortality (OR = 1.10, 95% CI 0.83–1.46, p = 0.43, I2 = 84%), severity (OR = 0.99, 95% CI 0.68–1.45, p = 0.98, I2 = 84%), or healthcare resource utilization (SMD = 0.03, 95% CI 0.06–0.12, p = 0.54, I2 = 37%) in patients with COVID-19 compared to those not taking ACEIs or ARBs. The multivariate meta-regression analysis model explained 63%, 31%, and 100% of the sources of heterogeneity for the three outcome indicators. Conclusions: The use of ACEIs and ARBs is not significantly correlated with mortality, severity, or healthcare resource utilization in patients with COVID-19, indicating safe clinical use of the medications. 2025-02-18 ARM, Vol. 93, Pages 4: A Meta-Analysis of the Impact of Using Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin II Receptor Blockers (ARBs) on Mortality, Severity, and Healthcare Resource Utilization in Patients with COVID-19

Advances in Respiratory Medicine doi: 10.3390/arm93010004

Authors: Ruijuan Li Jie Zhang Liang Ren

Objective: The primary objective of this study is to explore the potential link between the utilization of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and its impact on mortality, disease severity, and healthcare resource utilization in individuals diagnosed with COVID-19. We aim to establish a solid theoretical foundation for safe and effective clinical medications. Methods: We conducted a comprehensive search of various databases, including CNKI, PubMed, Science, Cell, Springer, Nature, Web of Science, and Embase. We also traced the literature of the included studies to ensure a thorough analysis of the available evidence. After applying a set of inclusion and exclusion criteria, we ultimately included a total of 41 articles in our analysis. To determine the overall effect size for dichotomous variables, we used the Mantel–Haenszel odds ratio in random effect models. For continuous variables, we calculated the inverse variance SMD using random effect models. To assess the outcomes and heterogeneity, we considered p-values (p < 0.05) and I2 values for all outcomes. We performed multivariate and univariate meta-regression analyses using the maximum likelihood approach with the CMA 3.0 software. Results: The results of our analysis indicated that the use of ACEIs or ARBs did not significantly influence mortality (OR = 1.10, 95% CI 0.83–1.46, p = 0.43, I2 = 84%), severity (OR = 0.99, 95% CI 0.68–1.45, p = 0.98, I2 = 84%), or healthcare resource utilization (SMD = 0.03, 95% CI 0.06–0.12, p = 0.54, I2 = 37%) in patients with COVID-19 compared to those not taking ACEIs or ARBs. The multivariate meta-regression analysis model explained 63%, 31%, and 100% of the sources of heterogeneity for the three outcome indicators. Conclusions: The use of ACEIs and ARBs is not significantly correlated with mortality, severity, or healthcare resource utilization in patients with COVID-19, indicating safe clinical use of the medications.

]]> A Meta-Analysis of the Impact of Using Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin II Receptor Blockers (ARBs) on Mortality, Severity, and Healthcare Resource Utilization in Patients with COVID-19 Ruijuan Li Jie Zhang Liang Ren doi: 10.3390/arm93010004 Advances in Respiratory Medicine 2025-02-18 Advances in Respiratory Medicine 2025-02-18 93 1 Review 4 10.3390/arm93010004 https://www.mdpi.com/2543-6031/93/1/4 ARM, Vol. 93, Pages 3: Prospective, Open-Label, Observational, Multicenter, Single Arm, Post-Marketing Study in Asthmatic Patients for Evaluation of Safety and Effectiveness of Indacaterol/Mometasone DPI (PROMISING-SHIFT) https://www.mdpi.com/2543-6031/93/1/3 Background: Asthma significantly impacts global health, necessitating effective management strategies. A combination of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABA) is recommended for patients with inadequately controlled asthma. Method: This prospective, open-label, multicenter study (PROMISING-SHIFT) study evaluated the safety and efficacy of once-daily Indacaterol/Mometasone (IND/MF) dry powder inhaler (DPI) in Indian asthma patients (≥12 years), inadequately controlled with prior therapies. Patients received IND/MF DPI in three strengths (150/80 mcg, 150/160 mcg, 150/320 mcg) over 12 weeks. Results: The study included a total of 174 participants, and 27 adverse events (AEs) in 25 patients (14.37%) were reported, primarily mild to moderate, with no serious adverse events (SAEs). Drug-related treatment-emergent adverse events (TEAEs) were observed in 11 patients. Significant improvements were noted in the mean trough FEV1 and FVC, increasing from baseline to week 4 and week 12 (p < 0.001). The mean ACQ-5 score significantly decreased from 3.0 ± 0.73 baseline to 2.50 ± 0.53 (16.67%) at week 4 and further to 1.73 ± 0.35 at week 12, along with reduced exacerbations (p < 0.001). The need for rescue medication declined from 13.79% to 8.62%, and 96.55% of patients reported treatment satisfaction by study completion. Conclusion: Once-daily IND/MF DPI demonstrated a favorable safety profile with marked improvements in lung function, asthma control, and patient satisfaction, making it a promising option for long-term asthma management in Indian patients. 2025-02-06 ARM, Vol. 93, Pages 3: Prospective, Open-Label, Observational, Multicenter, Single Arm, Post-Marketing Study in Asthmatic Patients for Evaluation of Safety and Effectiveness of Indacaterol/Mometasone DPI (PROMISING-SHIFT)

Advances in Respiratory Medicine doi: 10.3390/arm93010003

Authors: Saurabh Karmakar Gajendra V. Singh Amit S. Bhate Vijaykumar Barge Bharat Mehrotra Chintan Patel Ekta Sinha Sagar Bhagat Saiprasad Patil Hanmant Barkate

Background: Asthma significantly impacts global health, necessitating effective management strategies. A combination of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABA) is recommended for patients with inadequately controlled asthma. Method: This prospective, open-label, multicenter study (PROMISING-SHIFT) study evaluated the safety and efficacy of once-daily Indacaterol/Mometasone (IND/MF) dry powder inhaler (DPI) in Indian asthma patients (≥12 years), inadequately controlled with prior therapies. Patients received IND/MF DPI in three strengths (150/80 mcg, 150/160 mcg, 150/320 mcg) over 12 weeks. Results: The study included a total of 174 participants, and 27 adverse events (AEs) in 25 patients (14.37%) were reported, primarily mild to moderate, with no serious adverse events (SAEs). Drug-related treatment-emergent adverse events (TEAEs) were observed in 11 patients. Significant improvements were noted in the mean trough FEV1 and FVC, increasing from baseline to week 4 and week 12 (p < 0.001). The mean ACQ-5 score significantly decreased from 3.0 ± 0.73 baseline to 2.50 ± 0.53 (16.67%) at week 4 and further to 1.73 ± 0.35 at week 12, along with reduced exacerbations (p < 0.001). The need for rescue medication declined from 13.79% to 8.62%, and 96.55% of patients reported treatment satisfaction by study completion. Conclusion: Once-daily IND/MF DPI demonstrated a favorable safety profile with marked improvements in lung function, asthma control, and patient satisfaction, making it a promising option for long-term asthma management in Indian patients.

]]> Prospective, Open-Label, Observational, Multicenter, Single Arm, Post-Marketing Study in Asthmatic Patients for Evaluation of Safety and Effectiveness of Indacaterol/Mometasone DPI (PROMISING-SHIFT) Saurabh Karmakar Gajendra V. Singh Amit S. Bhate Vijaykumar Barge Bharat Mehrotra Chintan Patel Ekta Sinha Sagar Bhagat Saiprasad Patil Hanmant Barkate doi: 10.3390/arm93010003 Advances in Respiratory Medicine 2025-02-06 Advances in Respiratory Medicine 2025-02-06 93 1 Article 3 10.3390/arm93010003 https://www.mdpi.com/2543-6031/93/1/3 ARM, Vol. 93, Pages 2: The Role of Impulse Oscillometry in Detection of Preserved Ratio Impaired Spirometry (PRISm) https://www.mdpi.com/2543-6031/93/1/2 Background: Information is limited regarding the role of impulse oscillometry (IOS) for the detection of preserved ratio impaired spirometry (PRISm). Therefore, we aimed to study the diagnostic ability of IOS in differentiating between PRISm and healthy subjects. Methods: This retrospective data collection was done at the Lung Health Center, Faculty of Medicine, Chiang Mai University, Thailand between July 2019 and April 2022. The potential diagnostic possibilities of difference in resistance at 5 Hz (R5) and resistance at 20 Hz (R20) (R5-R20) for PRISm detection were analyzed. Results: The prevalence of PRISm was higher when using the fixed ratio (FR) criteria (FEV1/FVC ≥0.7 with FEV1 < 80% of predicted value) compared to the lower limit of normal (LLN) criteria (FEV1/FVC ≥ LLN and FEV1 < LLN) (10.0% vs. 4.2%). The %prediction for R5-R20 provided an acceptable area under the curve (AUC) for PRISm, defined by the LLN and the FR criteria (AuROC = 0.75 (95%CI; 0.64, 0.85) and 0.72 (95%CI; 0.63, 0.81), respectively). The cut-off value of %predicted R5-R20 ≥120% resulted in the highest sensitivity and specificity for detecting PRISm. Conclusions: The %predicted of R5-R20 ≥ 120% showed an acceptable performance for PRISm detection and PRISm may be detected by IOS. 2025-01-27 ARM, Vol. 93, Pages 2: The Role of Impulse Oscillometry in Detection of Preserved Ratio Impaired Spirometry (PRISm)

Advances in Respiratory Medicine doi: 10.3390/arm93010002

Authors: Chalerm Liwsrisakun Warawut Chaiwong Athavudh Deesomchok Pilaiporn Duangjit Chaicharn Pothirat

Background: Information is limited regarding the role of impulse oscillometry (IOS) for the detection of preserved ratio impaired spirometry (PRISm). Therefore, we aimed to study the diagnostic ability of IOS in differentiating between PRISm and healthy subjects. Methods: This retrospective data collection was done at the Lung Health Center, Faculty of Medicine, Chiang Mai University, Thailand between July 2019 and April 2022. The potential diagnostic possibilities of difference in resistance at 5 Hz (R5) and resistance at 20 Hz (R20) (R5-R20) for PRISm detection were analyzed. Results: The prevalence of PRISm was higher when using the fixed ratio (FR) criteria (FEV1/FVC ≥0.7 with FEV1 < 80% of predicted value) compared to the lower limit of normal (LLN) criteria (FEV1/FVC ≥ LLN and FEV1 < LLN) (10.0% vs. 4.2%). The %prediction for R5-R20 provided an acceptable area under the curve (AUC) for PRISm, defined by the LLN and the FR criteria (AuROC = 0.75 (95%CI; 0.64, 0.85) and 0.72 (95%CI; 0.63, 0.81), respectively). The cut-off value of %predicted R5-R20 ≥120% resulted in the highest sensitivity and specificity for detecting PRISm. Conclusions: The %predicted of R5-R20 ≥ 120% showed an acceptable performance for PRISm detection and PRISm may be detected by IOS.

]]> The Role of Impulse Oscillometry in Detection of Preserved Ratio Impaired Spirometry (PRISm) Chalerm Liwsrisakun Warawut Chaiwong Athavudh Deesomchok Pilaiporn Duangjit Chaicharn Pothirat doi: 10.3390/arm93010002 Advances in Respiratory Medicine 2025-01-27 Advances in Respiratory Medicine 2025-01-27 93 1 Article 2 10.3390/arm93010002 https://www.mdpi.com/2543-6031/93/1/2 ARM, Vol. 93, Pages 1: Evaluating the Effect of Body Mass Index on Procalcitonin Level in Patients with Pneumonia: A Retrospective Cross-Sectional Study https://www.mdpi.com/2543-6031/93/1/1 Procalcitonin (PCT) is commonly used to evaluate the etiology and severity of pneumonia. PCT has been shown to be elevated at baseline in patients with obesity. The aim of this study is to determine if body mass index (BMI) has an influence on admission PCT level in patients admitted to the hospital with a diagnosis of pneumonia. We conducted a retrospective cohort study that encompassed patient visits to a tertiary care center from 2014 until September 2023. A total of 18,652 patients presented to the emergency department with a diagnosis of pneumonia. A total of 3659 were admitted to the floor, and 2246 were admitted to the MICU. Patients were grouped based on admission BMI into five categories. The Kruskal–Wallis test performed on patients admitted to the floor revealed a statistically significant difference in PCT levels among groups of different BMIs (H = 34.97, df = 4, p < 0.001). In patients admitted to the MICU, the Kruskal–Wallis test revealed a significant difference in PCT levels among groups of different BMIs (H = 32.92, df = 4, p < 0.001). BMI has a statistically significant effect on PCT in patients admitted to the hospital with pneumonia. Patients with higher BMI may exhibit less robust PCT levels, which may impact management decisions. 2025-01-26 ARM, Vol. 93, Pages 1: Evaluating the Effect of Body Mass Index on Procalcitonin Level in Patients with Pneumonia: A Retrospective Cross-Sectional Study

Advances in Respiratory Medicine doi: 10.3390/arm93010001

Authors: Mohammad Z. Khrais J. Curran Henson Jake Smith Nikhil Meena

Procalcitonin (PCT) is commonly used to evaluate the etiology and severity of pneumonia. PCT has been shown to be elevated at baseline in patients with obesity. The aim of this study is to determine if body mass index (BMI) has an influence on admission PCT level in patients admitted to the hospital with a diagnosis of pneumonia. We conducted a retrospective cohort study that encompassed patient visits to a tertiary care center from 2014 until September 2023. A total of 18,652 patients presented to the emergency department with a diagnosis of pneumonia. A total of 3659 were admitted to the floor, and 2246 were admitted to the MICU. Patients were grouped based on admission BMI into five categories. The Kruskal–Wallis test performed on patients admitted to the floor revealed a statistically significant difference in PCT levels among groups of different BMIs (H = 34.97, df = 4, p < 0.001). In patients admitted to the MICU, the Kruskal–Wallis test revealed a significant difference in PCT levels among groups of different BMIs (H = 32.92, df = 4, p < 0.001). BMI has a statistically significant effect on PCT in patients admitted to the hospital with pneumonia. Patients with higher BMI may exhibit less robust PCT levels, which may impact management decisions.

]]> Evaluating the Effect of Body Mass Index on Procalcitonin Level in Patients with Pneumonia: A Retrospective Cross-Sectional Study Mohammad Z. Khrais J. Curran Henson Jake Smith Nikhil Meena doi: 10.3390/arm93010001 Advances in Respiratory Medicine 2025-01-26 Advances in Respiratory Medicine 2025-01-26 93 1 Communication 1 10.3390/arm93010001 https://www.mdpi.com/2543-6031/93/1/1 ARM, Vol. 92, Pages 559-572: Successful Therapy over 12 Months of People with Cystic Fibrosis with Rare Non-phe508del Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations with Elexacaftor/Tezacaftor/Ivacaftor (ETI) https://www.mdpi.com/2543-6031/92/6/49 Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator therapy approved for people with cystic fibrosis (pwCF) who have at least one phe508del mutation. However, its approval in the European Union (EU) for pwCF with non-phe508del mutations is lacking, because data on treatment response in this subgroup are scarce. Methods: This retrospective observational study evaluated six pwCF (ages 6 to 66) with responsive CFTR mutations (M1101K, R347P, 2789+5G>A, G551D) undergoing off-label ETI therapy. Evaluations were conducted at 0, 3, 6, 9, and 12 months, assessing lung function (FEV1), sweat chloride levels, body mass index (BMI), quality of life, medication satisfaction, ear, nose and throat (ENT) symptoms, and physical activity. A control group of four pwCF with classic symptoms and no ETI treatment was included. Results: FEV1 improved significantly after 3 and 6 months (p < 0.05) and stabilized by 12 months. Sweat chloride levels decreased significantly, with four pwCF achieving levels <60 mmol/L. Improvements in the upper and lower airway symptoms, medication satisfaction, and increased BMI were noted. Conclusions: ETI demonstrates high efficacy in this small group of pwCF with rare CFTR mutations, offering a treatment option that warrants further monitoring and evaluation. 2024-12-20 ARM, Vol. 92, Pages 559-572: Successful Therapy over 12 Months of People with Cystic Fibrosis with Rare Non-phe508del Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations with Elexacaftor/Tezacaftor/Ivacaftor (ETI)

Advances in Respiratory Medicine doi: 10.3390/arm92060049

Authors: Tomke Sütering Sebastian F. N. Bode Rainald Fischer Dorit Fabricius

Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator therapy approved for people with cystic fibrosis (pwCF) who have at least one phe508del mutation. However, its approval in the European Union (EU) for pwCF with non-phe508del mutations is lacking, because data on treatment response in this subgroup are scarce. Methods: This retrospective observational study evaluated six pwCF (ages 6 to 66) with responsive CFTR mutations (M1101K, R347P, 2789+5G>A, G551D) undergoing off-label ETI therapy. Evaluations were conducted at 0, 3, 6, 9, and 12 months, assessing lung function (FEV1), sweat chloride levels, body mass index (BMI), quality of life, medication satisfaction, ear, nose and throat (ENT) symptoms, and physical activity. A control group of four pwCF with classic symptoms and no ETI treatment was included. Results: FEV1 improved significantly after 3 and 6 months (p < 0.05) and stabilized by 12 months. Sweat chloride levels decreased significantly, with four pwCF achieving levels <60 mmol/L. Improvements in the upper and lower airway symptoms, medication satisfaction, and increased BMI were noted. Conclusions: ETI demonstrates high efficacy in this small group of pwCF with rare CFTR mutations, offering a treatment option that warrants further monitoring and evaluation.

]]> Successful Therapy over 12 Months of People with Cystic Fibrosis with Rare Non-phe508del Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations with Elexacaftor/Tezacaftor/Ivacaftor (ETI) Tomke Sütering Sebastian F. N. Bode Rainald Fischer Dorit Fabricius doi: 10.3390/arm92060049 Advances in Respiratory Medicine 2024-12-20 Advances in Respiratory Medicine 2024-12-20 92 6 Brief Report 559 10.3390/arm92060049 https://www.mdpi.com/2543-6031/92/6/49 ARM, Vol. 92, Pages 548-558: Association Between Visceral Fat and Lung Function Impairment in Overweight and Grade I Obese Women: A Cross-Sectional Study https://www.mdpi.com/2543-6031/92/6/48 Beyond the common comorbidities related to obesity, such as type 2 diabetes and cardiovascular diseases, impaired lung function is already known, but whether the fat distribution (sub-cutaneous, visceral) affects the lung function and pulmonary immune response are poorly known. Few evidence has shown that visceral fat is associated with insulin resistance, low-grade inflammation, and reduced lung function. In the present study, the body composition and fat distribution were evaluated by multi-frequency octopolar bioimpedance. This study demonstrated a possible association of increased visceral fat with impaired lung function in obesity grade I (n = 28; 45.46 ± 10.38 years old) women that was not observed in normal weight (n = 20; 43.20 ± 10.78 years old) and in overweight women (n = 30; 47.27 ± 10.25 years old). We also identified a negative correlation in FVC% (R2 = 0.9129; p < 0.0236), FEV1% (R2 = 0.1079; p < 0.0134), PEF% (R2 = 0.1673; p < 0.0018), and VC IN% (R2 = 0.1330; p < 0.0057) in the obesity grade I group, clearly demonstrating that higher levels of visceral fat correlate with reduced lung function, but not with sub-cutaneous fat. In addition, for the first time, a negative correlation among anti-fibrotic protein klotho (R2 = 0.09298; p < 0.0897) and anti-inflammatory IL-10 (R2 = 0.1653; p < 0.0487) in plasma was observed, in contrast to increased visceral fat. On the contrary, in breath condensate, a positive correlation for adiponectin (R2 = 0.5665; p < 0.0120), IL1-Ra (R2 = 0.2121; p < 0.0544), and IL1-Beta (R2 = 0.3270; p < 0.0084) was found. Thus, increased visceral fat directly influences the impairment of lung function and the systemic and pulmonary immune response of women with obesity grade I. 2024-12-18 ARM, Vol. 92, Pages 548-558: Association Between Visceral Fat and Lung Function Impairment in Overweight and Grade I Obese Women: A Cross-Sectional Study

Advances in Respiratory Medicine doi: 10.3390/arm92060048

Authors: Anamei Silva-Reis Boris Brill Maysa Alves Rodrigues Brandao-Rangel Renilson Moraes-Ferreira Dobroslav Melamed Helida Cristina Aquino-Santos Claudio Ricardo Frison Regiane Albertini Rodrigo Álvaro Brandao Lopes-Martins Luís Vicente Franco de Oliveira Gustavo Paixao-Santos Carlos Rocha Oliveira Asghar Abbasi Rodolfo P. Vieira

Beyond the common comorbidities related to obesity, such as type 2 diabetes and cardiovascular diseases, impaired lung function is already known, but whether the fat distribution (sub-cutaneous, visceral) affects the lung function and pulmonary immune response are poorly known. Few evidence has shown that visceral fat is associated with insulin resistance, low-grade inflammation, and reduced lung function. In the present study, the body composition and fat distribution were evaluated by multi-frequency octopolar bioimpedance. This study demonstrated a possible association of increased visceral fat with impaired lung function in obesity grade I (n = 28; 45.46 ± 10.38 years old) women that was not observed in normal weight (n = 20; 43.20 ± 10.78 years old) and in overweight women (n = 30; 47.27 ± 10.25 years old). We also identified a negative correlation in FVC% (R2 = 0.9129; p < 0.0236), FEV1% (R2 = 0.1079; p < 0.0134), PEF% (R2 = 0.1673; p < 0.0018), and VC IN% (R2 = 0.1330; p < 0.0057) in the obesity grade I group, clearly demonstrating that higher levels of visceral fat correlate with reduced lung function, but not with sub-cutaneous fat. In addition, for the first time, a negative correlation among anti-fibrotic protein klotho (R2 = 0.09298; p < 0.0897) and anti-inflammatory IL-10 (R2 = 0.1653; p < 0.0487) in plasma was observed, in contrast to increased visceral fat. On the contrary, in breath condensate, a positive correlation for adiponectin (R2 = 0.5665; p < 0.0120), IL1-Ra (R2 = 0.2121; p < 0.0544), and IL1-Beta (R2 = 0.3270; p < 0.0084) was found. Thus, increased visceral fat directly influences the impairment of lung function and the systemic and pulmonary immune response of women with obesity grade I.

]]> Association Between Visceral Fat and Lung Function Impairment in Overweight and Grade I Obese Women: A Cross-Sectional Study Anamei Silva-Reis Boris Brill Maysa Alves Rodrigues Brandao-Rangel Renilson Moraes-Ferreira Dobroslav Melamed Helida Cristina Aquino-Santos Claudio Ricardo Frison Regiane Albertini Rodrigo Álvaro Brandao Lopes-Martins Luís Vicente Franco de Oliveira Gustavo Paixao-Santos Carlos Rocha Oliveira Asghar Abbasi Rodolfo P. Vieira doi: 10.3390/arm92060048 Advances in Respiratory Medicine 2024-12-18 Advances in Respiratory Medicine 2024-12-18 92 6 Article 548 10.3390/arm92060048 https://www.mdpi.com/2543-6031/92/6/48 ARM, Vol. 92, Pages 538-547: Characterization of Serum Cytokine Patterns in Frequent-Exacerbation Asthma: Implications for Phenotyping and Management https://www.mdpi.com/2543-6031/92/6/47 (1) Background: Asthma exacerbations represent significant clinical events, however, the underlying inflammatory mechanisms and cytokine profiles in patients with frequent exacerbations remain incompletely understood; (2) Methods: In this prospective, cross-sectional study of 120 stable asthma patients, we compared the serum concentrations of eight key cytokines (IL-4, IL-12, IL-13, IL-17, IFN-α, IFN-γ, TNF-α, and IL-1β) between two groups: 60 patients with frequent exacerbations (≥ 2 events per year) and 60 matched controls with few exacerbations (1 event per year); (3) Results: Patients with frequent exacerbations showed significantly higher serum concentrations of IL-4 and IL-13 (p < 0.05), along with an increased prevalence of allergic history and comorbidities (chronic rhinosinusitis, GERD, OSA; all p < 0.05). The IgE levels correlated positively with IFN-α (rh = 0.26) and TNF-α (rh = 0.29), while the FeNO levels correlated with IL-17 (rh = 0.26) and IL-1β (rh = 0.33) (all p < 0.05); (4) Conclusions: Our findings identify a distinct cytokine signature in frequent exacerbators characterized by elevated IL-4 and IL-13 levels. The correlations between specific cytokines and established biomarkers suggest potential mechanisms underlying exacerbation susceptibility, which may inform targeted therapeutic strategies for this high-risk population. 2024-12-17 ARM, Vol. 92, Pages 538-547: Characterization of Serum Cytokine Patterns in Frequent-Exacerbation Asthma: Implications for Phenotyping and Management

Advances in Respiratory Medicine doi: 10.3390/arm92060047

Authors: Dao Ngoc Bang Pham Dac The Pham Thi Kim Nhung Nguyen Tien Dung Bach Quoc Tuan Vu Minh Duong Le Thi Dieu Hien Ta Ba Thang

(1) Background: Asthma exacerbations represent significant clinical events, however, the underlying inflammatory mechanisms and cytokine profiles in patients with frequent exacerbations remain incompletely understood; (2) Methods: In this prospective, cross-sectional study of 120 stable asthma patients, we compared the serum concentrations of eight key cytokines (IL-4, IL-12, IL-13, IL-17, IFN-α, IFN-γ, TNF-α, and IL-1β) between two groups: 60 patients with frequent exacerbations (≥ 2 events per year) and 60 matched controls with few exacerbations (1 event per year); (3) Results: Patients with frequent exacerbations showed significantly higher serum concentrations of IL-4 and IL-13 (p < 0.05), along with an increased prevalence of allergic history and comorbidities (chronic rhinosinusitis, GERD, OSA; all p < 0.05). The IgE levels correlated positively with IFN-α (rh = 0.26) and TNF-α (rh = 0.29), while the FeNO levels correlated with IL-17 (rh = 0.26) and IL-1β (rh = 0.33) (all p < 0.05); (4) Conclusions: Our findings identify a distinct cytokine signature in frequent exacerbators characterized by elevated IL-4 and IL-13 levels. The correlations between specific cytokines and established biomarkers suggest potential mechanisms underlying exacerbation susceptibility, which may inform targeted therapeutic strategies for this high-risk population.

]]> Characterization of Serum Cytokine Patterns in Frequent-Exacerbation Asthma: Implications for Phenotyping and Management Dao Ngoc Bang Pham Dac The Pham Thi Kim Nhung Nguyen Tien Dung Bach Quoc Tuan Vu Minh Duong Le Thi Dieu Hien Ta Ba Thang doi: 10.3390/arm92060047 Advances in Respiratory Medicine 2024-12-17 Advances in Respiratory Medicine 2024-12-17 92 6 Article 538 10.3390/arm92060047 https://www.mdpi.com/2543-6031/92/6/47 ARM, Vol. 92, Pages 526-537: Prevalence and Clinical Implications of Pulmonary Vein Stenosis in Bronchiectasis: A 3D Reconstruction CT Study https://www.mdpi.com/2543-6031/92/6/46 Background: Recent studies on bronchiectasis have revealed significant structural abnormalities and pathophysiological changes. However, there is limited research focused on pulmonary venous variability and congenital variation. Through our surgical observations, we noted that coarctation of pulmonary veins and atrophied lung volume are relatively common in bronchiectasis patients. Therefore, we conducted a retrospective study to explore pulmonary venous variation and secondary manifestations in bronchiectasis cases, utilizing 3D reconstruction software (Mimics Innovation Suite 21.0, Materialise Dental, Leuven, Belgium) to draw conclusions supported by statistical evidence. Method: This retrospective study included patients with bronchiectasis and healthy individuals who underwent CT examinations at Beijing Chao-Yang Hospital between January 2017 and July 2023. Chest CT data were reconstructed using Materialise Mimics. Pulmonary veins and lung lobes were segmented from surrounding tissue based on an appropriate threshold determined by local grey values and image gradients. Subsequently, venous cross-sectional areas and lung volumes were measured for statistical analysis. Result: CT data from 174 inpatients with bronchiectasis and 75 cases from the health examination center were included. Three-dimensional reconstruction data revealed a significant reduction in cross-sectional areas of pulmonary veins in the left lower lobe (p < 0.001), the right lower lobe (p = 0.030), and the right middle lobe (p = 0.009) of bronchiectasis patients. Subgroup analyses indicated that approximately 73.5% of localized cases of the left lower lobe exhibited pulmonary vein stenosis, while in the diffuse group, this proportion was only 52.6%. Furthermore, the cross-sectional area of pulmonary veins had a gradually decreasing trend, based on a small sample. Lung function tests showed significant reductions in FEV1, FVC, and FEV1% in bronchiectasis patients, attributed to the loss of lung volume in the left lower lobe, which accounted for 60.9% of the included sample. Conclusions: Our recent findings suggest that pulmonary venous stenosis is a common variation in bronchiectasis and is often observed concurrently with reduced lung volume, particularly affecting the left lower lobe. Moreover, localized cases are more likely to suffer from pulmonary venous stenosis, with an ambiguous downtrend as the disease progresses. In conclusion, increased attention to pulmonary venous variation in bronchiectasis is warranted, and exploring new therapies to intervene in the early stages or alleviate obstruction may be beneficial. 2024-12-16 ARM, Vol. 92, Pages 526-537: Prevalence and Clinical Implications of Pulmonary Vein Stenosis in Bronchiectasis: A 3D Reconstruction CT Study

Advances in Respiratory Medicine doi: 10.3390/arm92060046

Authors: Xin Li Yang Gu Jinbai Miao Ying Ji Mingming Shao Bin Hu

Background: Recent studies on bronchiectasis have revealed significant structural abnormalities and pathophysiological changes. However, there is limited research focused on pulmonary venous variability and congenital variation. Through our surgical observations, we noted that coarctation of pulmonary veins and atrophied lung volume are relatively common in bronchiectasis patients. Therefore, we conducted a retrospective study to explore pulmonary venous variation and secondary manifestations in bronchiectasis cases, utilizing 3D reconstruction software (Mimics Innovation Suite 21.0, Materialise Dental, Leuven, Belgium) to draw conclusions supported by statistical evidence. Method: This retrospective study included patients with bronchiectasis and healthy individuals who underwent CT examinations at Beijing Chao-Yang Hospital between January 2017 and July 2023. Chest CT data were reconstructed using Materialise Mimics. Pulmonary veins and lung lobes were segmented from surrounding tissue based on an appropriate threshold determined by local grey values and image gradients. Subsequently, venous cross-sectional areas and lung volumes were measured for statistical analysis. Result: CT data from 174 inpatients with bronchiectasis and 75 cases from the health examination center were included. Three-dimensional reconstruction data revealed a significant reduction in cross-sectional areas of pulmonary veins in the left lower lobe (p < 0.001), the right lower lobe (p = 0.030), and the right middle lobe (p = 0.009) of bronchiectasis patients. Subgroup analyses indicated that approximately 73.5% of localized cases of the left lower lobe exhibited pulmonary vein stenosis, while in the diffuse group, this proportion was only 52.6%. Furthermore, the cross-sectional area of pulmonary veins had a gradually decreasing trend, based on a small sample. Lung function tests showed significant reductions in FEV1, FVC, and FEV1% in bronchiectasis patients, attributed to the loss of lung volume in the left lower lobe, which accounted for 60.9% of the included sample. Conclusions: Our recent findings suggest that pulmonary venous stenosis is a common variation in bronchiectasis and is often observed concurrently with reduced lung volume, particularly affecting the left lower lobe. Moreover, localized cases are more likely to suffer from pulmonary venous stenosis, with an ambiguous downtrend as the disease progresses. In conclusion, increased attention to pulmonary venous variation in bronchiectasis is warranted, and exploring new therapies to intervene in the early stages or alleviate obstruction may be beneficial.

]]> Prevalence and Clinical Implications of Pulmonary Vein Stenosis in Bronchiectasis: A 3D Reconstruction CT Study Xin Li Yang Gu Jinbai Miao Ying Ji Mingming Shao Bin Hu doi: 10.3390/arm92060046 Advances in Respiratory Medicine 2024-12-16 Advances in Respiratory Medicine 2024-12-16 92 6 Article 526 10.3390/arm92060046 https://www.mdpi.com/2543-6031/92/6/46 ARM, Vol. 92, Pages 504-525: Prospects for Treatment of Lung Cancer Using Activated Lymphocytes Combined with Other Anti-Cancer Modalities https://www.mdpi.com/2543-6031/92/6/45 This review explores the significance and prospects of using diverse T-cell variants in the context of combined therapy for lung cancer treatment. Recently, there has been an increase in research focused on understanding the critical role of tumor-specific T lymphocytes and the potential benefits of autologous T-cell-based treatments for individuals with lung cancer. One promising approach involves intravenous administration of ex vivo-activated autologous lymphocytes to improve the immune status of patients with cancer. Investigations are also exploring the factors that influence the success of T-cell therapy and the methods used to stimulate them. Achieving a comprehensive understanding of the characteristics of activated lymphocytes and deciphering the mechanisms underlying their activation of innate anti-tumor immunity will pave the way for numerous clinical trials and the development of innovative strategies for cancer therapy like combined immunotherapy and radiation therapy. 2024-12-06 ARM, Vol. 92, Pages 504-525: Prospects for Treatment of Lung Cancer Using Activated Lymphocytes Combined with Other Anti-Cancer Modalities

Advances in Respiratory Medicine doi: 10.3390/arm92060045

Authors: Anastasia Ganina Manarbek Askarov Larissa Kozina Madina Karimova Yerzhan Shayakhmetov Perizat Mukhamedzhanova Aigul Brimova Daulet Berikbol Elmira Chuvakova Lina Zaripova Abay Baigenzhin

This review explores the significance and prospects of using diverse T-cell variants in the context of combined therapy for lung cancer treatment. Recently, there has been an increase in research focused on understanding the critical role of tumor-specific T lymphocytes and the potential benefits of autologous T-cell-based treatments for individuals with lung cancer. One promising approach involves intravenous administration of ex vivo-activated autologous lymphocytes to improve the immune status of patients with cancer. Investigations are also exploring the factors that influence the success of T-cell therapy and the methods used to stimulate them. Achieving a comprehensive understanding of the characteristics of activated lymphocytes and deciphering the mechanisms underlying their activation of innate anti-tumor immunity will pave the way for numerous clinical trials and the development of innovative strategies for cancer therapy like combined immunotherapy and radiation therapy.

]]> Prospects for Treatment of Lung Cancer Using Activated Lymphocytes Combined with Other Anti-Cancer Modalities Anastasia Ganina Manarbek Askarov Larissa Kozina Madina Karimova Yerzhan Shayakhmetov Perizat Mukhamedzhanova Aigul Brimova Daulet Berikbol Elmira Chuvakova Lina Zaripova Abay Baigenzhin doi: 10.3390/arm92060045 Advances in Respiratory Medicine 2024-12-06 Advances in Respiratory Medicine 2024-12-06 92 6 Review 504 10.3390/arm92060045 https://www.mdpi.com/2543-6031/92/6/45 ARM, Vol. 92, Pages 485-503: Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective https://www.mdpi.com/2543-6031/92/6/44 Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe condition characterized by persistent obstruction and vascular remodeling in the pulmonary arteries following an acute pulmonary embolism (APE). Although APE is a significant risk factor, up to 25% of CTEPH cases occur without a history of APE or deep vein thrombosis, complicating the understanding of its pathogenesis. Herein, we carried out a narrative review discussing the mechanisms involved in CTEPH development, including fibrotic thrombus formation, pulmonary vascular remodeling, and abnormal angiogenesis, leading to elevated pulmonary vascular resistance and right heart failure. We also outlined how the disease’s pathophysiology reveals both proximal and distal pulmonary artery obstruction, contributing to the development of pulmonary hypertension. We depicted the risk factors predicting CTEPH, including thrombotic history, hemostatic disorders, and certain medical conditions. We finally looked at the molecular mechanisms behind the role of endothelial dysfunction, gene expression alterations, and inflammatory processes in CTEPH progression and detection. Despite these insights, there is still a need for improved diagnostic tools, biomarkers, and therapeutic strategies to enhance early detection and management of CTEPH, ultimately aiming to reduce diagnostic delay and improve patient outcomes. 2024-11-27 ARM, Vol. 92, Pages 485-503: Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective

Advances in Respiratory Medicine doi: 10.3390/arm92060044

Authors: Leslie Marisol Gonzalez-Hermosillo Guillermo Cueto-Robledo Dulce Iliana Navarro-Vergara Maria Berenice Torres-Rojas Marisol García-Cesar Oscar Pérez-Méndez Galileo Escobedo

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe condition characterized by persistent obstruction and vascular remodeling in the pulmonary arteries following an acute pulmonary embolism (APE). Although APE is a significant risk factor, up to 25% of CTEPH cases occur without a history of APE or deep vein thrombosis, complicating the understanding of its pathogenesis. Herein, we carried out a narrative review discussing the mechanisms involved in CTEPH development, including fibrotic thrombus formation, pulmonary vascular remodeling, and abnormal angiogenesis, leading to elevated pulmonary vascular resistance and right heart failure. We also outlined how the disease’s pathophysiology reveals both proximal and distal pulmonary artery obstruction, contributing to the development of pulmonary hypertension. We depicted the risk factors predicting CTEPH, including thrombotic history, hemostatic disorders, and certain medical conditions. We finally looked at the molecular mechanisms behind the role of endothelial dysfunction, gene expression alterations, and inflammatory processes in CTEPH progression and detection. Despite these insights, there is still a need for improved diagnostic tools, biomarkers, and therapeutic strategies to enhance early detection and management of CTEPH, ultimately aiming to reduce diagnostic delay and improve patient outcomes.

]]> Molecular Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: A Clinical Update from a Basic Research Perspective Leslie Marisol Gonzalez-Hermosillo Guillermo Cueto-Robledo Dulce Iliana Navarro-Vergara Maria Berenice Torres-Rojas Marisol García-Cesar Oscar Pérez-Méndez Galileo Escobedo doi: 10.3390/arm92060044 Advances in Respiratory Medicine 2024-11-27 Advances in Respiratory Medicine 2024-11-27 92 6 Review 485 10.3390/arm92060044 https://www.mdpi.com/2543-6031/92/6/44 ARM, Vol. 92, Pages 472-484: Association Between Weight-Adjusted Waist Index and Emphysema in Adults in the United States: A Cross-Sectional Study Involving 44,949 Participants https://www.mdpi.com/2543-6031/92/6/43 Background: The relationship between obesity and respiratory diseases has been widely explored. In this context, the Weight-Adjusted Waist Index (WWI) has emerged as a novel metric for assessing visceral fat. This study aims to evaluate the association between WWI and the risk of emphysema in the U.S. population, by utilizing data from the 2001–2018 National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional study was conducted using NHANES data from 2001 to 2018. Logistic regression models were applied to assess the relationship between WWI and emphysema risk. Interaction and subgroup analyses were performed to explore effect modifiers. Results: Our study included a total of 44,949 American adults. The results of the multivariable logistic regression analysis revealed an association between WWI and the incidence of emphysema. In the fully adjusted model, the probability of developing emphysema was 1.5 times higher in the group with WWI > 10.46 compared to those with WWI ≤ 10.46, with an odds ratio of [1.5 (1.1, 1.9), p = 0.003]. Subgroup analysis showed stronger associations among males, non-Hispanic Whites, and individuals with hypertension. Furthermore, we used a two-piece linear regression model and found a nonlinear association between WWI and emphysema, with a breakpoint at 12.5. Conclusions: Our findings indicate a significant association between WWI levels and emphysema. Larger-scale prospective studies are needed to further explore the role of WWI in emphysema. 2024-11-21 ARM, Vol. 92, Pages 472-484: Association Between Weight-Adjusted Waist Index and Emphysema in Adults in the United States: A Cross-Sectional Study Involving 44,949 Participants

Advances in Respiratory Medicine doi: 10.3390/arm92060043

Authors: Hui Cheng Ziheng Yang Jiateng Guo Yukun Zu Fan Li Bo Zhao

Background: The relationship between obesity and respiratory diseases has been widely explored. In this context, the Weight-Adjusted Waist Index (WWI) has emerged as a novel metric for assessing visceral fat. This study aims to evaluate the association between WWI and the risk of emphysema in the U.S. population, by utilizing data from the 2001–2018 National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional study was conducted using NHANES data from 2001 to 2018. Logistic regression models were applied to assess the relationship between WWI and emphysema risk. Interaction and subgroup analyses were performed to explore effect modifiers. Results: Our study included a total of 44,949 American adults. The results of the multivariable logistic regression analysis revealed an association between WWI and the incidence of emphysema. In the fully adjusted model, the probability of developing emphysema was 1.5 times higher in the group with WWI > 10.46 compared to those with WWI ≤ 10.46, with an odds ratio of [1.5 (1.1, 1.9), p = 0.003]. Subgroup analysis showed stronger associations among males, non-Hispanic Whites, and individuals with hypertension. Furthermore, we used a two-piece linear regression model and found a nonlinear association between WWI and emphysema, with a breakpoint at 12.5. Conclusions: Our findings indicate a significant association between WWI levels and emphysema. Larger-scale prospective studies are needed to further explore the role of WWI in emphysema.

]]> Association Between Weight-Adjusted Waist Index and Emphysema in Adults in the United States: A Cross-Sectional Study Involving 44,949 Participants Hui Cheng Ziheng Yang Jiateng Guo Yukun Zu Fan Li Bo Zhao doi: 10.3390/arm92060043 Advances in Respiratory Medicine 2024-11-21 Advances in Respiratory Medicine 2024-11-21 92 6 Article 472 10.3390/arm92060043 https://www.mdpi.com/2543-6031/92/6/43 ARM, Vol. 92, Pages 466-471: Beneficial Impact of Vaccination Against SARS-CoV-2 on the Mental Health of IPF Patients https://www.mdpi.com/2543-6031/92/6/42 Background: Depression and anxiety represent significant comorbidities in idiopathic pulmonary fibrosis (IPF) patients, affecting their quality of life. The COVID-19 pandemic has had an uneven impact on global mental health. The Hospital Anxiety and Depression Scale (HADS) constitutes a validated tool to identify anxiety disorders and depression. The aim of this multicentre study was to evaluate the effect of COVID-19 vaccination on depression and anxiety in IPF patients. Methods: Consecutive IPF patients (median 73.5 years) who are regularly followed-up with were included in the study. Demographics, functional, and clinical were recorded. The HADS score was calculated before and one month after vaccination against COVID-19 in all participants. A Wilcoxon signed ranks test was conducted. Results: A total of 180 IPF patients (median 73.5 years) were included in the study. Among them, 145 patients (81%) received antifibrotic treatment. A significant reduction in HADS, both in anxiety and depression scales, was observed one month after vaccination against SARS-COV-2), independent of age, smoking, lung function impairment, and prior history of depression (p < 0.01). Conclusions: A higher Hospital Anxiety and Depression Scale score was detected before vaccination against COVID-19. It seems that vaccination also offered a beneficial effect on depression and anxiety in IPF patients, independent of age, smoking, lung function impairment, and prior history of depression. 2024-11-06 ARM, Vol. 92, Pages 466-471: Beneficial Impact of Vaccination Against SARS-CoV-2 on the Mental Health of IPF Patients

Advances in Respiratory Medicine doi: 10.3390/arm92060042

Authors: Ioannis Tomos Andriana I. Papaioannou Zoe I. Daniil Ilias E. Dimeas Paraskevi Kirgou Athena Gogali Konstantinos Tatsis Ilias Papanikolaou Vasilios Tzilas Argyrios Tzouvelekis Panayiota Tsiri Paschalis Steiropoulos Pachalis Ntolios Areti Xyfteri Katerina Antoniou Emmanouil Symvoulakis Aggeliki Haritou Maria Maniati Lykourgos Kolilekas Elvira-Markella Antonogiannaki Vasiliki Apollonatou Maria Kallieri Kostas Samaras Stylianos Loukides Anna Karakatsani Demosthenes Bouros Effrosyni Manali Spyros Papiris

Background: Depression and anxiety represent significant comorbidities in idiopathic pulmonary fibrosis (IPF) patients, affecting their quality of life. The COVID-19 pandemic has had an uneven impact on global mental health. The Hospital Anxiety and Depression Scale (HADS) constitutes a validated tool to identify anxiety disorders and depression. The aim of this multicentre study was to evaluate the effect of COVID-19 vaccination on depression and anxiety in IPF patients. Methods: Consecutive IPF patients (median 73.5 years) who are regularly followed-up with were included in the study. Demographics, functional, and clinical were recorded. The HADS score was calculated before and one month after vaccination against COVID-19 in all participants. A Wilcoxon signed ranks test was conducted. Results: A total of 180 IPF patients (median 73.5 years) were included in the study. Among them, 145 patients (81%) received antifibrotic treatment. A significant reduction in HADS, both in anxiety and depression scales, was observed one month after vaccination against SARS-COV-2), independent of age, smoking, lung function impairment, and prior history of depression (p < 0.01). Conclusions: A higher Hospital Anxiety and Depression Scale score was detected before vaccination against COVID-19. It seems that vaccination also offered a beneficial effect on depression and anxiety in IPF patients, independent of age, smoking, lung function impairment, and prior history of depression.

]]> Beneficial Impact of Vaccination Against SARS-CoV-2 on the Mental Health of IPF Patients Ioannis Tomos Andriana I. Papaioannou Zoe I. Daniil Ilias E. Dimeas Paraskevi Kirgou Athena Gogali Konstantinos Tatsis Ilias Papanikolaou Vasilios Tzilas Argyrios Tzouvelekis Panayiota Tsiri Paschalis Steiropoulos Pachalis Ntolios Areti Xyfteri Katerina Antoniou Emmanouil Symvoulakis Aggeliki Haritou Maria Maniati Lykourgos Kolilekas Elvira-Markella Antonogiannaki Vasiliki Apollonatou Maria Kallieri Kostas Samaras Stylianos Loukides Anna Karakatsani Demosthenes Bouros Effrosyni Manali Spyros Papiris doi: 10.3390/arm92060042 Advances in Respiratory Medicine 2024-11-06 Advances in Respiratory Medicine 2024-11-06 92 6 Brief Report 466 10.3390/arm92060042 https://www.mdpi.com/2543-6031/92/6/42