Search Results (230)

Recent documents from leading international pediatric respiratory societies have strongly encouraged the use of lung function tests in clinical practice and research. These tests can explore ventilatory function across its volumetric and temporal domains, providing information on the intrapulmonary location and extent of damage caused by respiratory diseases. The choice of which test to use in each case to investigate presenting respiratory symptoms depends on the patient’s symptoms and the diagnostic–therapeutic phase being addresse d. In the most common and representative chronic pediatric condition—bronchial asthma—lung function tests play an especially important role due to the disease’s complexity and the fluctuating nature of airway obstruction. This review aims to examine the potential of various lung function tests in asthma, helping clinicians and researchers to optimize diagnosis and follow-up with the most appropriate methodology. While spirometry and flow resistance measurements using the interrupter technique have historically been the cornerstones of diagnosis and clinical monitoring in childhood asthma, the advent of new technologies—such as multiple breath nitrogen washout (MBNW) and the forced oscillation technique (FOT)—is opening up the door to a more nuanced view of the disease. These tools allow for an evaluation of asthma as a structurally complex and topographically and temporally disorganized condition. FOT, in particular, facilitates measurement acceptability in less cooperative subjects, both in respiratory physiology labs and even at the patient’s home. Full article

The FOT is a non-invasive method for assessing respiratory mechanics. It enables the measurement of respiratory system impedance by applying pressure oscillations through a loudspeaker at the subject mouth and then studying its deformation, which is commensurate to the resistance opposed by the respiratory system. The main parameters which can be determined with the FOT are the impedance (Z) and the components of respiratory resistance (Rrs) and reactance (Xrs). The FOT has been predominantly applied to the study of respiratory mechanics for research purposes; however, preclinical experiments and subsequently observational clinical studies have demonstrated that FOT can effectively assess airway obstruction, bronchodilator response, bronchial hyperresponsiveness, and the presence of small airways disease. More recently, studies on the FOT in restrictive lung diseases have also been reported. Nonetheless, international guidelines on the precise applications of the FOT in lung diseases are still lacking. The aim of the review was to describe the technical aspects related to the FOT methodology in clinical practice and to provide a concise state of the art on the applications of the FOT in obstructive and restrictive lung diseases. Full article

Metastatic dissemination defines a complex phenomenon driven by genetic forces and, importantly, determined by interaction between cancer cells and the surrounding stroma. Although the biologic and immune reactions which characterize the process have been widely and extensively evaluated, fewer data are available regarding the mechanical and physical forces to which circulating neoplastic clones are exposed. It should be hypothesized that this interaction can be modified in case of concomitant pathologic conditions, such as chronic vasculopathy, which frequently occurs in lung cancer patients. We here aim at analyzing and discussing the complex interplay between lung malignant transformation and arteriopathy, mainly focusing on the immune–inflammatory systemic reaction. Notably—in most instances—smoking-related fixed airflow obstruction, including but not limited to COPD, frequently coexists and contributes to both tumor progression and vascular complications. Attention is paid mainly to the analysis of the role of immune checkpoint inhibitors and their interaction with triple bronchodilation and antiaggregants. Understanding the biomechanical and molecular dynamics of lung cancer progression in altered vascular territories has several translational implications in defining risk stratification and in surgical planning and therapeutic targeting. Moreover, computational modeling of the physical forces which regulate the transit and extravasation of metastatic clones in altered contexts could be of help in deciphering the whole process and in determining more effective blockade strategies. Full article

Asthma is a persistent ailment that impacts the respiratory system and stands as a formidable public health challenge globally. Inhaled corticosteroids and bronchodilators, while effective in asthma management, are accompanied by side effects and high costs. Recently, nutraceuticals have gained significant attention as adjuvant therapy due to their promising outcomes. Given the antioxidant properties, nutrient richness, and an array of health benefits, beetroot and its bioactive compounds have been tested as an adjuvant therapy for asthma management. Although its main bioactive compound, betalains (betanin), has demonstrated promising results in mouse studies, beetroot juice has been found to worsen asthma. This review investigated the full spectrum of active compounds associated with beetroots to understand the underlying factors contributing to the conflicting findings. The finding suggests that individual bioactive compounds, such as phenolic compounds, flavonoids, nitrates, betalains, saponins, vitamins, fiber, and carotenoids, possess asthma-managing properties. However, the consumption of juice may exacerbate the condition. This discrepancy may be attributed to the presence of sugars and oxalates in the juice, which could counteract the beneficial effects of the bioactive compounds. Full article

Background/Objective: The COVID-19 pandemic profoundly transformed social life worldwide, indiscriminately affecting individuals across all age groups. Children have not been exempted from the risk of severe illness and death caused by COVID-19. Objective: This paper sought to describe the clinical findings, laboratory and imaging results, and hospital care provided for severe and critical cases of COVID-19 in unvaccinated children, with or without severe asthma, hospitalized in a public referral service for COVID-19 treatment in the Brazilian state of Pernambuco. Methods: This was a case series study of severe and critical COVID-19 in hospitalized, unvaccinated children, with or without severe asthma, conducted in a public referral hospital between March 2020 and June 2021. Results: The case series included 80 children, aged from 1 month to 11 years, with the highest frequency among those under 2 years old (58.8%) and a predominance of males (65%). Respiratory diseases, including severe asthma, were present in 73.8% of the cases. Pediatric multisystem inflammatory syndrome occurred in 15% of the children, some of whom presented with cardiac involvement. Oxygen therapy was required in 65% of the cases, mechanical ventilation in 15%, and 33.7% of the children required intensive care in a pediatric intensive care unit. Pulmonary infiltrates and ground-glass opacities were common findings on chest X-rays and CT scans; inflammatory markers were elevated, and the most commonly used medications were antibiotics, bronchodilators, and corticosteroids. Conclusions: This case series has identified key characteristics of children with severe and critical COVID-19 during a period when vaccines were not yet available in Brazil for the study age group. However, the persistence of low vaccination coverage, largely due to parental vaccine hesitancy, continues to leave children vulnerable to potentially severe illness from COVID-19. These findings may inform the development of public health emergency contingency plans, as well as clinical protocols and care pathways, which can guide decision-making in pediatric care and ensure appropriate clinical management, ultimately improving the quality of care provided. Full article

Background and Objectives: The common complaints of head and neck cancer patients receiving concurrent chemo-radiotherapy (CCRT) are dry mouth, dysphagia, trismus, hoarseness, sore throat, and oral mucosal damage, which result in retained secretions and difficult expectoration. We aimed to investigate the effect of adjuvant respiratory therapy on secretion expectoration and treatment completion in patients with head and neck cancer receiving CCRT. Materials and Methods: From November 2016 to May 2018, 56 head and neck cancer patients were recruited retrospectively, and according to their respiratory therapy in the medical record, were divided into the control group (CG, n = 27) or the research group (RG, n = 29). In the CG, the patients were treated via the teaching of routine breathing exercises and expel techniques, while patients in the RG were treated with the inhalation of a ß-agonist bronchodilator agent five times each week, in addition to the standard treatment administered in the CG. Results: The total completion rate of treatment was significantly higher in the RG (21 patients) compared with the CG (12 patients) (72.4% vs. 44.4%, p < 0.05). After therapy, the rates of clinical symptoms were significantly increased in the RG compared with the CG, including smooth expectoration (76.2% vs. 75.0%), decreased secretions (61.9% vs. 58.3%), reduced viscosity of secretions (66.7% vs. 58.3%), lower cough frequency (71.4% vs. 50.0%), improved sore throat (52.4% vs. 41.7%), and swallowing function (52.4% vs. 50.0%). The continuation of chemo-radiotherapy without disruption was higher in the RG than it was in the CG (66.7% vs. 50.0%). There was no significant difference in adverse effects between the two groups. Conclusions: Adjuvant respiratory therapy not only improves secretion expectoration, but also reduces side effects, thus promoting the completion of the CCRT schedule in patients with head and neck cancer. Full article

Background: Patients with mild coronavirus disease 2019 (COVID-19) are usually managed in an outpatient setting. Pulmonary functions in this setting have not been explored. This study aimed to determine abnormal lung functions in COVID-19 patients under a home isolation program. Methods: A prospective study was conducted in asymptomatic or mild COVID-19 patients with normal chest radiographs at two medical centers in Thailand. Spirometry data, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), forced expiratory flow at 25–75% of FVC (FEF25–75), and bronchodilator responsiveness (BDR), were collected. Spirometry was performed after disease resolution at baseline and 3-month follow-up. Abnormal lung functions were classified into airway obstruction, restrictive defect, mixed defect, small airway disease, and BDR. Results: A total of 250 patients (58% female) were included. The mean age was 37.4 ± 15.2 years. Asymptomatic patients accounted for 7.6%. Common symptoms included fever (55.6%) and cough (60.0%). Abnormal lung functions were observed in 28.4% of patients, with a restrictive lung pattern (14.4%), airway obstruction (4.8%), mixed defect (0.4%), small airway disease (8.4%), and BDR (2.8%). Significant changes from baseline were noted in FVC (1.21%), FEV₁/FVC (−1.51%predicted), PEF (0.06%), and FEF_25–75 (−2.76%). Logistic regression analysis indicated that a higher body mass index was associated with a lower risk of abnormal lung function. Conclusions: Ventilatory defects were observed in one-third of patients with mild COVID-19 who did not require hospitalization, mainly presenting as restrictive patterns and small airway disease. Even mild cases may have residual pulmonary impairment, warranting further long-term studies. Full article

G-protein-coupled receptors (GPCRs) are vital transmembrane proteins that regulate a wide range of physiological processes by transmitting extracellular signals into intracellular responses. Among them, the β2-adrenergic receptor (β2-AR) plays a central role in bronchodilation, smooth muscle relaxation, and cardiovascular modulation, making it a key therapeutic target for diseases such as asthma, chronic obstructive pulmonary disease (COPD), and hypertension. This study explores the potential of natural bioactive compounds like ephedrine, quercetin, catechin, and resveratrol as alternative ligands for β2-AR through molecular docking analysis. Using AutoDock 4.6, these compounds were docked with the binding site of the β2-AR (PDB ID: 2RH1), and their binding affinities and interaction map were evaluated. Results showed that all compounds exhibited favorable binding energies and stable interactions with key receptor residues, with quercetin demonstrating the highest affinity. The findings suggest that these natural compounds may serve as promising leads for the development of safer, plant-derived modulators of β2-AR, supporting the role of computational approaches in natural product-based drug discovery. However, as docking cannot determine functional activity, these findings should be interpreted as preliminary and require experimental validation. Full article

Objectives: Although patients with bronchiectasis tend to have obstructive nonreversible lung functions, some have bronchodilator response (BDR), and a relatively large number are treated with bronchodilators. We assessed BDR in patients with cystic fibrosis (CF) and other bronchiectatic diseases and healthy controls (HCs) in a randomized controlled setup. Methods: Patients with cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and non-CF non-PCD bronchiectasis (non-CF/PCD), as well as HCs, were recruited. Participants were randomly assigned to receive salbutamol (four puffs) and then a placebo or a placebo and then salbutamol. BDR was calculated using the American Thoracic Society (ATS)/European Respiratory Society (ERS) standard, defined as the change related to the individual’s predicted value (new method) or to the initial value (old method). Results: Sixty-nine patients (CF = 30, PCD = 20, non-CF/PCD = 19) and 20 HCs were included. Patients with CF and PCD (but not non-CF/PCD) had a statistically greater mean response to salbutamol compared with the placebo, (CF–salbutamol first: 2.82 vs. 0.85%, p = 0.01; placebo first: 2.39 vs. −0.27%, p = 0.02; PCD–salbutamol first: 5.32 vs. 1.88%, p = 0.01; placebo first: 2.24 vs. 0.77%, p = 0.05). Few patients had significant BDR (new method, >10%)—CF (0), PCD (2), non-CF/PCD (0) and HCs (2)): using the old method, an additional PCD patient and three non-CF/PCD had significant BDR (>12%). Conclusions: Significant BDR seems to be rare in patients with bronchiectasis. In CF and PCD, the response was greater than the placebo; the clinical significance of this difference and its therapeutic implications, as well as the best method to determine BDR, have yet to be determined. Full article

Asthma is a highly heterogeneous respiratory disease that, in its severe forms, is characterized by persistent symptoms, frequent exacerbations, and a significant impact on patients’ quality of life. Despite high-dose inhaled corticosteroids and long-acting bronchodilators, a subset of patients remains uncontrolled, necessitating advanced therapeutic strategies. The advent of biologic therapies has revolutionized the management of severe asthma, offering targeted interventions based on the underlying inflammatory endotypes, primarily T2-high and T2-low. However, selecting the most appropriate biologic remains challenging due to overlapping phenotypic features and the limited availability of validated biomarkers. This narrative review explores the clinical utility of key biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin, and total and specific IgE, in guiding biologic therapy. All the information provided is based on an extensive literature search conducted on PubMed. We also examine the clinical characteristics and comorbidities that influence therapeutic choices. Furthermore, we present a practical decision-making platform, including a clinical table matching phenotypes with biologic agents, such as omalizumab, mepolizumab, benralizumab, dupilumab, and tezepelumab. By integrating biomarker analysis with clinical assessment, based on current guidelines and our extensive real-life experience, we aim to offer a logical framework to help clinicians select the most suitable biologic treatment for patients with uncontrolled severe asthma. Future research should focus on identifying novel biomarkers, refining patient stratification, and evaluating long-term outcomes to further advance precision medicine in the management of severe asthma. Full article

Background: The associations between physical activity (PA) and all-cause mortality remain under-investigated among individuals with impaired lung function. Methods: With 201,596 participants from the UK Biobank cohort, baseline pre-bronchodilation lung function tests and a modified International Physical Activity Questionnaire were used to assess lung function status (normal, restricted, obstructed) and PA attributes (volume, intensity, duration). All-cause mortality was determined through linkage to the National Health Services Register. Cox proportional hazard regression was applied to characterize the associations between PA metrics and all-cause mortality among people with different lung function statuses. Dose–response relationships between PA metrics and all-cause mortality risks were examined using restricted cubic splines (number of knots = 4). Results: Over a 11.81-year median follow-up, 5.24% of participants died. All-cause mortality risk declined with increasing total PA volume, plateauing at 1800 MET-min/week without further reduction in individuals with and without impaired lung function. Similar trends were observed for PA intensity and duration, with both factors demonstrating reduced mortality risk that plateaued after reaching a specific threshold. Notably, 24.1% (95% CI: 16.7%, 30.8%) and 43.1% (95% CI: 36.1%, 49.7%) lower mortality risk was observed among individuals with and without impaired lung function for PA with 1201–1800 MET-min/wk. Conclusions: PA was associated with a decreased risk of all-cause mortality among individuals with and without impaired lung function, suggesting that those with impaired lung function might also benefit from PA. Full article

G-protein-coupled receptors (GPCRs) are a group of various membrane proteins that mediate essential physiological processes by translating extracellular signals into intracellular responses. The β2-Adrenergic Receptor (β2-AR), a key GPCR, plays a critical role in smooth muscle relaxation, bronchodilation, and cardiovascular function, making it an important therapeutic target for diseases such as asthma and hypertension. Diketopiperazines (DPKs), as cyclic peptides, have shown promise as scaffolds for inhibiting protein interactions and modulating receptor activity, offering a potential alternative to traditional small-molecule inhibitors with reduced side effects. In this study, five DPK derivatives were selected from the PubChem database and evaluated for their binding affinity to the 3D structure of β2-AR (PDB ID = 2RH1) through molecular docking studies using AutoDock 4.6 and MGLTools. The binding energy and hydrogen bond formation of each compound were evaluated to determine their interaction efficiency. Among the compounds, tryptophan-proline diketopiperazine (compound 3) exhibited the highest binding affinity with a binding energy of −5.89 kcal/mol. This enhanced interaction is attributed to the aromatic nature of tryptophan, which promotes strong π-π stacking interactions, and the rigidity of proline, which optimally fits within the receptor’s binding pocket. Hydrophobic interactions further stabilized the complex. These findings highlight compound 3 as a promising β2-AR modulator, providing valuable insights for the design of peptide-based inhibitors targeting β2-AR-related pathologies. Full article

Indomethacin, ibuprofen, and acetylsalicylic acid (ASA) are non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit prostaglandin (PG) synthesis. Previous studies in airway smooth muscle demonstrated that chronic exposure to testosterone (TES, 40 nM) enhances the relaxation induced by salbutamol and theophylline due to K⁺ channel increment, without modifying cyclooxygenase expression. This study examines how indomethacin, ibuprofen, and ASA affect K⁺ currents and the relaxation response to these bronchodilators. In organ baths, tracheas from young male guinea pigs chronically (48 h) treated with 40 nM TES showed increased relaxation to salbutamol and theophylline, which was completely abolished by indomethacin. Patch-clamp recordings revealed that TES increased salbutamol- and theophylline-induced K⁺ currents, and only indomethacin fully inhibited this potentiation; ibuprofen and ASA had partial effects. The involved currents included voltage-dependent K⁺ (K_V) and high-conductance Ca²⁺-activated K⁺ (BK_Ca) channels. Our results demonstrate that indomethacin exerts a dual action, inhibiting K⁺ channel activity and PG synthesis, unlike ibuprofen and ASA. This dual mechanism explains its stronger inhibitory effect on TES-enhanced ASM relaxation. These findings suggest that indomethacin may counteract the protective effects of TES, which promotes anti-inflammatory and smooth muscle-relaxing states. Therefore, it is advisable to exercise caution when prescribing indomethacin to young males with asthma, as the protective role of TES may diminish, potentially resulting in an exacerbation of asthma symptoms. Full article

Background/Objectives: Asthma outcomes in children and adolescents largely depend on parental adherence to prescribed treatment plans. This study investigates how the COVID-19 pandemic influenced parental decision-making in managing their children’s asthma, regardless of whether the children were infected with SARS-CoV-2. Material and method: In this research, 146 children with asthma were analyzed based on the following data: demographic parameters (gender, age group, and residence), before and after measurements of FeNO and pulmonary function test parameters were performed to assess the evolution of asthma for infected and non-infected children, exacerbations, parents’ compliance with the treatment, changes in treatment steps performed by physicians, and the GINA asthma control levels. Results: The effect of parent self-management of doses was evident in the variation of FeNO and pulmonary function test parameters before and after COVID-19 disease, including children with asthma who did not contract the virus, in the decrease in well-controlled asthma cases, as well as in the number of exacerbations per year. A step-down in treatment doses was statistically associated with increased FeNO values (p < 0.0005), and decreased FEV1 values (p = 0.025). Higher values of FeNO were statistically significantly associated with a higher number of exacerbations per year (p < 0.0005). There was a statistically significant moderately strong association between the treatment steps evolution (decided by the attending physician) and parents’ self-management of doses in the attempt to assess the control of the disease of children with asthma (p = 0.019). Also, 80.95% of children for whom the parents performed a step-down in dose no longer presented well-controlled asthma, leading to a statistically significant association relative to the level of asthma control and doses adjustments (p < 0.0005). Conclusions: During epidemiological circumstances, a strong collaboration between the parents/caregivers/pediatric patients with asthma and attending physicians is essential to correctly assess the symptoms and to comply the asthma treatment with ICS and a bronchodilator in order to control the disease. Full article

The aim of this narrative review is to explore possible connections that might lead to both obesity and asthma; it will explain factors and mechanisms involved in disease pathogenesis, focusing particularly on diet and nutrients, the microbiome, inflammatory and metabolic dysregulation, lung function, the genetics/genomics of obese asthma, risk of exacerbation, atopy, and response to treatment. It highlights the role that obesity plays as a risk factor for and disease modifier of asthma, understanding the evidence supporting lifestyle changes in influencing disease progression. Pathophysiological mechanisms in obesity-related asthma have influences on the course of disease pathology. Due to these factors, the child with obese asthma needs a specific therapeutic approach taking into account the common unresponsiveness to bronchodilators, increased requirements for controller medications, poorer steroid effectiveness, and better response to leukotriene receptor (LTR) inhibitors. Therapeutic strategies centered on prevention are suggested and the development of resources to assist families with weight loss strategies and lifestyle changes is shown to be useful for effective weight control and optimal asthma management. Obese children with asthma generally should receive interventions that encourage daily physical activity, weight loss, and normalization of nutrient levels, and monitoring of common obesity-related sequelae should be considered by healthcare providers managing obese children with difficult to control asthma. Recognizing and identifying an asthmatic patient is not always easy and a detailed medical history of the patient, with particular attention paid to their presenting and past symptoms, and a complete physical examination play pivotal and fundamental roles in determining the final diagnosis. Full article