Search Results (2,434)

Background: Pre-Chronic Obstructive Pulmonary Disease (pre-COPD) and Preserved Ratio Impaired Spirometry (PRISm) phenotypes represent important components of the early obstructive lung disease spectrum, characterized by respiratory symptoms and structural lung abnormalities prior to the development of overt airflow limitation. Emphysema is considered one of the major structural phenotypes underlying airway disease and the COPD spectrum. Although cigarette smoking is the best recognized risk factor for these conditions, non-tobacco exposures may also contribute to early structural lung changes. In this study, we evaluated the radiological features, pulmonary function parameters, and dyspnea severity of CT-detected emphysema in symptomatic patients classified as having pre-COPD or PRISm, with particular attention paid to the potential influence of smoking status on disease characteristics. Methods: In this retrospective, single-center study, symptomatic patients aged 20–50 years classified as having pre-COPD or PRISm and in whom emphysema was detected on high-resolution computed tomography (HRCT) were evaluated. Only symptomatic patients who underwent HRCT for clinical indications and in whom emphysema was identified were included. Demographic characteristics, emphysema type and quantitative emphysema severity, pulmonary function parameters, and Modified Medical Research Council (mMRC) dyspnea scores were analyzed. The PRISm and pre-COPD groups were compared in terms of clinical and symptomatic characteristics. In addition, smoking-related clinical and radiological characteristics were also evaluated. Results: A total of 232 patients were included in the study. The median age was 43 years (38–48), and 84.1% of the participants were male. Among the study population, 68.5% were classified in the pre-COPD group and 31.5% in the PRISm group. The most frequently identified emphysema patterns were paraseptal (44.4%) and centrilobular (40.5%). The median total lung emphysema area was 18% (13–22). A weak negative correlation was observed between the degree of emphysema and FEV₁ (r = −0.185; p = 0.005), whereas a weak positive correlation was found between emphysema extent and the mMRC dyspnea score (r = 0.214; p = 0.001). Dyspnea severity was significantly higher in the PRISm group compared with the pre-COPD group (p < 0.001). In the smoking-status subgroup analysis, ever-smokers demonstrated significantly greater dyspnea severity and lower FEV₁ values, whereas never-smokers had a significantly higher proportion of emphysema extent > 18% (all p < 0.05). Conclusions: Radiologically detected emphysema in symptomatic patients without airflow limitation was associated with statistically significant but weak alterations in pulmonary function and dyspnea burden. Dyspnea severity was significantly higher in the PRISm phenotype. In a smoking-status subgroup analysis, ever-smokers had significantly greater dyspnea severity, whereas never-smokers showed a significantly higher proportion of extensive emphysema (>18%), despite similar functional impairment across groups. These findings underscore the importance of non-tobacco exposures in the development of emphysema within pre-obstructive spirometric phenotypes. Multicenter prospective studies incorporating healthy controls and systematic exposure documentation are needed to confirm these observations. Full article

Antimicrobial resistance in Mycoplasma gallisepticum (MG), a primary causative agent of chronic respiratory disease in poultry, has reached alarming levels, underscoring the urgent need for alternative strategies. Natural products have emerged as promising candidates owing to their multi-target mechanisms of action. This review synthesizes current evidence on natural anti-MG agents, critically appraising their in vitro and in vivo efficacy, molecular mechanisms, and translational potential. A mechanistic taxonomy is proposed for distinguishing direct pathogen-directed mechanisms (membrane disruption, adhesion inhibition, virulence factor neutralization) from indirect host-directed mechanisms, notably NF-κB/MAPK pathway modulation and gut–lung axis immunoregulation. Emphasis is placed on anti-infective polypharmacology, exemplified by luteolin’s dual inhibition of the TatD virulence factor and host inflammatory cascades. The gut–lung axis represents a novel therapeutic frontier, with Bacillus subtilis KC1 controlling respiratory mycoplasmosis through intestinal microbiome remodeling and systemic AhR activation. Despite encouraging efficacy data, critical knowledge gaps persist, including a scarcity of rigorous in vivo trials under commercial conditions, incomplete mechanistic characterization, and challenges in standardizing complex natural product formulations. Natural products are best positioned not as wholesale antibiotic replacements but as integral components of integrated, antibiotic-sparing strategies aligned with antimicrobial stewardship and One Health principles. Full article

Phaeohyphomycosis is an opportunistic fungal infection caused by dematiaceous fungi and is considered uncommon in dogs, particularly when associated with visceral or systemic involvement. Pulmonary disease as a primary site of infection is rarely reported in veterinary medicine and is often associated with an unfavorable outcome. This report describes a fatal case of pulmonary phaeohyphomycosis in a dog, characterized by severe granulomatous pneumonia, vascular invasion by pigmented fungal hyphae, and the development of large vessel thrombosis. Histopathological examination revealed septate, pigmented hyphae consistent with dematiaceous fungi associated with an intense granulomatous inflammatory response. Although molecular analysis by polymerase chain reaction was unsuccessful due to the absence of amplifiable DNA in archived FFPE tissue, the clinicopathological correlation and histopathological findings were sufficient to support a diagnosis consistent with phaeohyphomycosis. Severe pulmonary inflammation likely contributed to vascular endothelial injury, resulting in pulmonary hypertension and thrombosis of major veins. This case highlights the diagnostic and clinical challenges associated with phaeohyphomycosis in dogs and emphasizes the importance of considering this infection in the differential diagnosis of chronic or progressive respiratory diseases accompanied by systemic complications. Furthermore, it reinforces the relevance of histopathology and comprehensive clinicopathological evaluation when molecular confirmation of the etiological agent is not achievable. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease that occurs due to fibrotic remodeling of the pulmonary vessels. This leads to increased pressure overload onto the right ventricle, resulting in complications such as heart failure. Pulmonary endarterectomy (PEA) remains the gold standard of treatment for CTEPH, yet many patients experience life-threatening perioperative complications, including refractory right ventricular failure, reperfusion pulmonary edema, and endobronchial hemorrhage. Extracorporeal membrane oxygenation (ECMO) has been used as a form of mechanical circulatory support to aid recovery in patients with perioperative complications in the context of CTEPH. This review identifies preoperative risk factors, including pulmonary vascular resistance, high body mass index, and elevated neutrophil-to-lymphocyte ratios. It also identifies differences in ECMO configuration, with veno-arterial ECMO preferred for hemodynamic instability and veno-venous ECMO for respiratory failure. Finally, we posit that, based on contemporary literature, the implementation of early ECMO in decompensated patients may be associated with reduced hospital mortality, and in those who survive beget excellent mid-term survival. Full article

Chronic respiratory diseases (CRDs) represent a significant global mortality burden, largely driven by viral-triggered exacerbations. In the elderly, susceptibility to viral pathogens is critically linked to the “interferon gap”—a kinetic delay in innate antiviral signaling resulting from immunosenescence and Th2-skewed inflammaging. While traditional vaccines provide pathogen-specific protection, their efficacy is often compromised by age-related immune hyporesponsiveness and antigenic drift. This perspective paper proposes a dual-phase, virus-agnostic immunomodulatory platform designed to restore mucosal immune competence and provide a rapid-response intervention for incipient exacerbations. Rather than acting as a pathogen-specific vaccine, the platform serves as a comprehensive host immune-rejuvenation engine and cellular adjuvant platform. The platform consists of two integrated stages: Allopriming and Alloantigen Inhalation Recall (AIR). Allopriming utilizes AlloStim^® (activated, allogeneic Th1 cells) to leverage the evolutionarily conserved allo-rejection response, establishing a lung mucosal reservoir of allo-specific Th1 tissue-resident memory cells (Trm). Building on previously published Phase I/II data showing that Allopriming reverses biomarkers of immunosenescence and sustains durable heterologous antiviral responsiveness, the AIR strategy is introduced as a patient-administered rescue mechanism for frail CRD patients. AIR is designed to activate pre-positioned Trm cells at the earliest onset of symptoms, inducing a high-magnitude IFN-γ surge in the lung mucosa. By bridging the senescent “interferon gap” with the rapid effector kinetics of Trm activation, this approach represents a novel paradigm toward reconstituting youthful-like antiviral mucosal immunity to both enhance vaccine efficacy in the elderly and protect against both seasonal pathogens and emerging viral triggers (“Disease X”) of CRD. Future randomized studies in long-term care settings are planned to evaluate clinical outcomes in high-risk populations. Full article

Chronic obstructive pulmonary disease remains a leading cause of death worldwide, with emphysema contributing significantly to dyspnea, exercise limitation, and mortality. Bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBVs) has emerged as a minimally invasive, reversible alternative to lung volume reduction surgery for carefully selected patients with severe emphysema who remain symptomatic despite optimal medical therapy. EBVs are one-way valves placed bronchoscopically to achieve complete lobar occlusion, inducing atelectasis of the most diseased lung segments while allowing better ventilated parenchyma to expand, thereby improving respiratory mechanics and reducing hyperinflation. Landmark randomized controlled trials demonstrated that BLVR using EBVs produces significant improvements in forced expiratory volume in one second (FEV₁), exercise capacity, and quality of life comparable to surgical lung volume reduction but with reduced morbidity and mortality. Critical to treatment success is meticulous patient selection based on emphysema distribution, absence of collateral ventilation, and appropriate physiologic parameters. Pneumothorax represents the most common serious complication, occurring in approximately 26% of patients, though paradoxically, it indicates successful lobar occlusion and predicts favorable long-term outcomes. As the most extensively studied BLVR, endobronchial valve therapy represents a cornerstone intervention for appropriately selected patients with severe emphysema. Full article

Liver fibrosis is a chronic disease diagnosed through invasive methods that can worsen patients’ health. Moreover, this disease is diagnosed in terminal stages, when the damage is already widespread and irreversible, which makes it necessary to have minimally invasive diagnostic methods with high performance. The aim was to compare research on non-invasive methods, respiratory footprint, and volatile organic compounds for the diagnosis of liver fibrosis through patient exhalation. Following the PRISMA guidelines, systematic searches were conducted in 13 databases. We could identify 17,454 documents between 2009 and 2022. Inclusion criteria comprised original investigations using Gas Chromatography–Mass Spectrometry (GC-MS), Ion Mobility–Mass Spectrometer (IMR-MS), and e-nose for liver fibrosis diagnosis. We considered the precision, specificity, and sensitivity of each test and the methodological quality of each study according to the PEDro guideline. Seven investigations were included. Four (57%) studies used GC-MS, and two (28.6%) used e-nose. The most commonly used gold standard was liver biopsy, and all studies were of European origin, with only adult populations. Three (42%) studies had a specificity >90%, and five (71.4%) had a sensitivity between 85 and 100%. Isoprene is the most significant and distinguishable biomarker for liver fibrosis diagnosis. Five (71.4%) studies had high methodological quality. GC-MS is the most used technique for detecting liver fibrosis, and isoprene is the most frequent volatile organic compound (VOC) found in the exhalation of patients with liver fibrosis. More studies are needed in areas with high risk and prevalence of hepatic fibrosis. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition where many patients are given antibiotics like amoxicillin and macrolides (clarithromycin, azithromycin, roxithromycin) for bacterial infections. Recent concerns about clarithromycin’s potential link to cardiovascular events have arisen, despite its effectiveness against respiratory pathogens. This study aims to compare the cardiovascular risk of macrolide antibiotics versus amoxicillin in suspected COPD patients. Method: We used the Danish National Health Service Prescription Database (DNHSP) to identify COPD patients and their use of antibiotics. The included COPD patients were divided into four groups: amoxicillin users, roxithromycin users, clarithromycin users and azithromycin users. Data from multiple registries were merged to track hospitalizations, causes of death, and major adverse cardiovascular events (MACEs) as the primary endpoint. Patients were followed for a 3-year period. We applied adjusted Cox regression and sensitivity analyses with IPTW and IPCW to address confounders and censoring. Results: Our study involved 45,869 patients who were prescribed a long-acting muscarinic antagonist, over the age of 40 years old and who received one of the following antibiotics: amoxicillin, azithromycin, clarithromycin, or roxithromycin. No increased risk of MACEs was observed in macrolide-treated patients compared to those treated with amoxicillin (azithromycin: HR 0.97: 95% CI 0.83–1.13 p = 0.69, clarithromycin: HR 1.06 95% CI 0.87–1.28 p = 0.57, roxithromycin: HR 1.04 95% CI 0.91–1.18 p = 0.60), as confirmed by the sensitivity analysis (azithromycin: HR 0.95 95% CI 0.82–1.11 p = 0.52, clarithromycin: HR 1.05 95% CI 0.87–1.27 p = 0.60, roxithromycin: HR 1.05 95% CI 0.92–1.19 p = 0.48). Similarly, hazard ratios for all-cause mortality and cardiovascular death among the antibiotic groups showed no significant statistical differences. Conclusions: These findings suggest that there is no difference in the risk of MACEs, all-cause mortality, or cardiovascular death between the amoxicillin group and the macrolide group in a large and unselected population of COPD patients. Full article

Asthma is the most prevalent chronic respiratory disease in childhood, and the objective assessment of airway inflammation remains a major challenge, particularly in younger children in whom conventional lung function testing is often not feasible. The aim of this narrative review is to evaluate the clinical role of fractional exhaled nitric oxide (FeNO) in pediatric asthma, focusing on its diagnostic utility, role in treatment guidance, and value in disease monitoring. A structured literature search was conducted in PubMed for studies published between January 2015 and October 2025, using predefined keywords related to FeNO, asthma, and pediatric populations. After applying the eligibility criteria, 47 studies were included in the final synthesis. Evidence from systematic reviews and clinical studies indicates that FeNO has moderate-to-good diagnostic accuracy for childhood asthma, with a pooled sensitivity of 0.79 and specificity of 0.81, and is most useful as an adjunct to clinical assessment and lung function testing. FeNO-guided therapy may reduce exacerbation rates in selected pediatric populations, although its effects on symptom control and corticosteroid use remain inconsistent. In the monitoring setting, serial FeNO measurements may provide additional information on inflammatory control, treatment adherence, and risk of future exacerbations. However, interpretation is influenced by multiple confounding factors, including atopy, allergic rhinitis, corticosteroid therapy, and asthma phenotype. In conclusion, FeNO is a valuable complementary biomarker in pediatric asthma, with particular utility in improving diagnostic and therapeutic precision. Its optimal use requires careful integration within a multimodal clinical framework rather than reliance as a standalone tool. Full article

Severe asthma (SA) is a chronic respiratory disease characterized by clinical heterogeneity and poor therapeutic response. Variants in the IL4 gene, including rs2243250 and rs2243248, have been associated with asthma susceptibility and severity in different populations; however, their role in the Mexican population remains unclear. This study evaluated the association of IL4 promoter variants rs2243250 and rs2243248 with SA and related clinical characteristics in a Mexican population using genetic and in silico approaches. In total, 106 patients with SA and 180 healthy individuals were included. Genotyping was performed using allelic discrimination assays with TaqMan^® probes, and associations between genotypes and clinical variables were assessed. No significant differences in allele or genotype frequencies were observed between groups. However, the rs2243250 TT genotype was associated with nocturnal symptoms (OR = 3.03, 95% CI = 1.31–7.00, p = 0.009) and increased use of rescue medication (OR = 3.16, 95% CI = 1.41–7.07, p = 0.005). The rs2243248 TG/GG genotypes were associated with epithelial allergy (p < 0.05). In silico analysis suggested a regulatory role for both variants. These findings suggest that IL4 variants may not influence overall disease risk but could modulate clinical features of asthma severity. Full article

SIRT2 (Sirtuin 2) is an NAD+-dependent deacetylase that exerts crucial regulatory effects on immune homeostasis and macrophage activation. While chronic cold exposure is a known predisposing factor for pulmonary dysfunction, the precise mechanisms by which SIRT2 potentially modulates lung macrophage polarization under cold stress remains poorly understood. In this study, we evaluated the protective capacity of SIRT2 using both wild-type (WT) and Sirt2-knockout (Sirt2−/−) murine models subjected to chronic cold exposure (4 °C for 3 h daily over 21 days). Our results demonstrated that Sirt2 deficiency significantly exacerbated cold-induced pulmonary histopathological damage and increased the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) (p < 0.05). Furthermore, chronic cold stress triggered a macrophage-centered inflammatory response, a process wherein SIRT2 was found to curtail M1 pro-inflammatory polarization. To further investigate these mechanisms, in vitro experiments were conducted using the mouse alveolar macrophage cell line MH-S. While LPS was utilized as a canonical inflammatory stimulus to mimic the injury environment, SIRT2 overexpression was found to reverse the LPS-induced increase in M1 markers and attenuate inflammatory cytokine secretion. These findings suggest that SIRT2 maintains intracellular homeostasis by modulating macrophage plasticity and plays a protective role in the development of chronic cold stimulus-induced lung injury. Consequently, SIRT2 activation may represent a potential therapeutic pathway for the treatment of environment-related respiratory diseases. Full article

Global climate change and air pollution jointly threaten respiratory health. Asthma, a prevalent chronic inflammatory airway disease, is exacerbated by both traditional air pollutants such as particulate matter (PM_2.5), ozone (O₃), nitrogen dioxide (NO₂), sulfur dioxide (SO₂) and emerging contaminants like microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS), with effects amplified under extreme temperature conditions. In reality, individuals face complex combined exposures, yet the synergistic effects of these factors on asthma pathogenesis remain poorly understood. This narrative review synthesizes epidemiological and toxicological evidence. It aims to elucidate both the individual and the notably synergistic effects of these factors on asthma pathogenesis. The central mechanistic pathway is initiated by oxidative stress, which activates key inflammatory signaling pathways, thereby driving immune imbalance and airway inflammation. Our review underscores that the combined exposure to traditional pollutants, emerging pollutants, and extreme temperatures may pose a greater threat than individual factors. These findings underscore the critical need for an integrated perspective in asthma research and public health policy. Moving beyond single-pollutant approaches, we advocate for combinatorial risk assessment and synergistic intervention strategies to effectively mitigate the growing burden of asthma in a changing climate. Full article

Acute respiratory failure (ARF) often leads to ICU admission, ventilatory support, illness, and death. The usual classification into hypoxemic and hypercapnic types does not capture its full complexity. Precision medicine uses the concept of “treatable traits” to guide care based on traits that are clinically relevant, identifiable, measurable, and possibly changeable. Arterial carbon dioxide pressure (PaCO₂) reflects factors like alveolar ventilation, dead space, respiratory mechanics, and how patients respond to ventilatory support. This makes it clinically relevant in selected situations. We carried out a scoping review using PRISMA-ScR and JBI guidelines to summarize evidence on hypocapnia and hypercapnia as prognostic, stratification, or clinically relevant variables during respiratory support. We searched PubMed/MEDLINE, ScienceDirect, and Web of Science (1994–2025), and checked references by hand. Thirty-four studies met our criteria and were grouped into four areas: pre-intubation or early acute presentation, non-invasive support (NIV/HFNC), invasive mechanical ventilation (IMV), and weaning or post-extubation. In summary, hypocapnia was linked to worse outcomes or failure of support in hypoxemic or cardiogenic cases. Hypercapnia helped identify patients who benefited from NIV, such as those with chronic obstructive pulmonary disease or obesity hypoventilation. For IMV, the effects depended on the presence and severity of acidosis and on its duration. Overall, PaCO₂ showed context-dependent clinical relevance, acting mainly as a prognostic or stratification marker and, in narrower settings, as a variable that may inform monitoring or support decisions. This review provides a pragmatic framework for interpreting PaCO₂ across respiratory support contexts and highlights the need for safe and clinically meaningful targets. Full article

Chronic obstructive pulmonary disease (COPD) imposes a substantial physical and psychosocial burden, yet the role of loneliness remains under-recognised in clinical practice. Loneliness, defined as a subjective discrepancy between desired and actual social relationships, has emerged as a clinically relevant determinant of patient outcomes. This narrative review synthesises current evidence on the epidemiology, mechanisms, and clinical consequences of loneliness in COPD, and evaluates its implications for disease management. Available evidence indicates that loneliness affects a considerable proportion of individuals with COPD, with prevalence estimates ranging from approximately 18% to over 30%, particularly among patients with greater symptom burden, functional limitation, and oxygen dependence. Dyspnoea and advancing disease severity reduce social participation and increase vulnerability to perceived social disconnection. Loneliness influences COPD outcomes through interconnected behavioural, biological, and healthcare engagement pathways, including systemic inflammation, neuroendocrine stress responses, physical inactivity, impaired self-management, and reduced engagement with healthcare services. These mechanisms contribute to poorer clinical trajectories, as loneliness is consistently associated with reduced health-related quality of life, increased exacerbations, higher healthcare utilisation, greater risk of hospitalisation, and elevated mortality, independent of depression and anxiety. Despite this, loneliness is rarely assessed in routine respiratory care, and targeted interventions remain limited. Emerging strategies, including pulmonary rehabilitation, peer support, and digital health interventions, show promise in reducing loneliness and improving outcomes. Loneliness represents a modifiable and clinically actionable risk factor in COPD, and its integration into routine assessment and management may enhance patient engagement, optimise treatment effectiveness, and reduce healthcare burden. Addressing loneliness represents a critical opportunity to advance more effective and comprehensive COPD care. Full article

Background: Fiberoptic bronchoscopy (FOB) is a procedure routinely performed in clinical practice for both diagnostic and therapeutic purposes. FOB frequently impairs respiratory function, which may exacerbate respiratory failure. Currently, conventional oxygen therapy (COT) is the most commonly used form of respiratory support; however, non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) are being used increasingly. The optimal settings and indications for NIV and HFNC in patients with respiratory acidosis undergoing FOB have not yet been determined. Methods: This is a prospective, multicenter, randomized controlled trial including two parallel study populations defined by the indication for bronchoscopy and the type of respiratory acidosis. Therapeutic FOB (Study 1): Patients with decompensated type 2 respiratory failure (pH < 7.35 and PaCO₂ > 45 mmHg) will be randomized to receive one of four methods of respiratory support during bronchoscopy: COT, NIV, HFNC, or invasive mechanical ventilation (IMV) (n = 315). Diagnostic FOB (Study 2): Patients with chronic respiratory acidosis (pH ≥ 7.35, PaCO₂ > 45 mmHg, and/or HCO₃⁻ > 27 mmol/L) will be randomized to receive COT, NIV, or HFNC during bronchoscopy (n = 210). Before FOB, patients in both groups will undergo arterial blood gas (ABG) analysis. During FOB, vital signs will be continuously monitored, including SpO₂, FiO₂, TcCO₂, ECG, and heart rate. After FOB, ABG analysis will be repeated, and study endpoints and complications, if any, will be recorded. The planned study period is from April 2026 to April 2029. Results: Based on the study results, we aim to evaluate the effectiveness and safety of different respiratory support strategies during flexible bronchoscopy, with the primary objective of comparing the rate of treatment failure among COT, HFNC, NIV, and IMV. Treatment failure is defined as the need for endotracheal intubation, premature termination of the procedure, or escalation of respiratory support. Additionally, we aim to identify the optimal NIV and HFNC settings, as well as complication rates in both study groups. Conclusions: The results of this study will help define the role of optimal respiratory support in patients with respiratory acidosis undergoing FOB, potentially leading to a shorter time from admission to diagnosis, better tolerance of the procedure, and faster recovery afterward. Full article