Respir Med [JOURNAL]
Sun
200 papers
Prediction of therapeutic effect of antifibrotic therapy for idiopathic pulmonary fibrosis using quantitative CT texture analysis.
Yabuuchi H, Sagiyama K, Tsubouchi K … +9 more , Hashisako M, Takano T, Yamasaki Y, Hida T, Hino T, Tashiro K, Nishizawa N, Kojima T, Ishigami K
Respir Med · 2026 Jul · PMID 42401375 · Publisher ↗
OBJECTIVES: To determine whether CT texture analysis can predict therapeutic response after antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS: Forty-one IPF patients treated with antifib...
OBJECTIVES: To determine whether CT texture analysis can predict therapeutic response after antifibrotic therapy for idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS: Forty-one IPF patients treated with antifibrotic drugs for more than 1 year were enrolled. Ratios of 7 lesion types (air space; consolidation; consolidation with bronchiectasis, i.e., fibrosis; ground-glass opacity; honeycombing; reticular opacity; and traction bronchiectasis), normal lungs, emphysema, and vascular-related structures were compared between responders and non-responders. Clinical and spirometric parameters were also compared. Univariate and multivariate logistic regression analyses were used to compare all parameters. Predictive capability was evaluated using a receiver operating characteristic (ROC) curve. Kaplan-Meier curves of overall survival were compared between the high ratio group and the low ratio group of the significant parameter. In a validation study, 25 IPF patients were examined. RESULTS: Fibrosis and traction bronchiectasis ratios showed significance in the univariate logistic regression analysis. Fibrosis ratio alone showed significance and revealed the best odds ratio (2.09) in the multivariate logistic regression analysis. Diagnostic capability of fibrosis ratio in upper lobes (AUC, 0.85) was superior to that of entire lung or lower lobes. Median overall survival for a high fibrosis ratio in upper lobes group was 41.6 months, and that for a low fibrosis ratio group was 69.2 months (P = 0.026). The validation study also yielded high diagnostic capability of F ratio in upper lobes (AUC, 0.83). CONCLUSION: Fibrosis ratio in upper lobes seems to be a promising tool for predicting therapeutic response in patients with IPF treated with antifibrotic drugs.
Obesity and Early Sepsis-Associated Acute Respiratory Distress Syndrome: A Prospective Multicenter Study.
Zhao L, Li Y, Lin X … +12 more , Cui Q, Liu J, Yang F, Wang Y, Wang J, Liu Y, Shi X, Cao D, Li J, Su F, Zhang H, Xie K
Respir Med · 2026 Jul · PMID 42401374 · Publisher ↗
PURPOSE: The role of obesity in sepsis-associated acute respiratory distress syndrome (SA-ARDS) remains uncertain, particularly amid evolving diagnostic criteria. We aimed to assess whether obesity differentially influen...
PURPOSE: The role of obesity in sepsis-associated acute respiratory distress syndrome (SA-ARDS) remains uncertain, particularly amid evolving diagnostic criteria. We aimed to assess whether obesity differentially influences SA-ARDS incidence and mortality under the Berlin definition versus an expanded framework incorporating high-flow nasal cannula (HFNC). METHODS: This prospective multicenter cohort study included 1,799 adults with sepsis 3.0 from three ICUs. SA-ARDS was diagnosed using (1) Berlin criteria and (2) a new definition integrating HFNC. The primary outcome was incidence of SA-ARDS. Secondary outcomes included 28- and 90-day mortality in SA-ARDS patients. RESULTS: Obesity was independently associated with elevated SA-ARDS incidence under the new definition (adjusted OR 5.61, 95% CI 4.56-6.92; AUC = 0.700), with even higher risk in ARDS patients under Berlin criteria (OR 6.66, 95% CI 5.01-8.91) and HFNC recipients (OR 5.77, 95% CI 3.85-8.85). These associations remained robust in PSM and IPW analyses. However, in ARDS patients of the new definition (including HFNC patients), no survival differences were observed across BMI categories. However, under the Berlin definition, obesity patients had significantly lower 90-day mortality than underweight and normal-weight patients, particularly in the elderly and those with prolonged hospital stays (P < 0.05). CONCLUSIONS: Obesity independently increased SA-ARDS risk across both diagnostic frameworks. However, the mortality benefit (Berlin definition) was absent when using the expanded criteria incorporating HFNC. This indicates obesity drives susceptibility but confers no universal survival advantage in new ARDS cohorts.
Adults with Congenital Lung Malformations: A Descriptive Analysis of an Underexplored Population.
Dossche LWJ, Heijne den Bak AM, Zuidweg MJP … +4 more , Ciet P, Caudri D, Schnater JM, Kamphuis LS
Respir Med · 2026 Jul · PMID 42398841 · Publisher ↗
INTRODUCTION: Congenital lung malformations (CLM) comprise various developmental respiratory tract anomalies. Long-term outcomes in adulthood remain poorly defined because structured follow-up often ends after childhood....
INTRODUCTION: Congenital lung malformations (CLM) comprise various developmental respiratory tract anomalies. Long-term outcomes in adulthood remain poorly defined because structured follow-up often ends after childhood. We aimed to determine the clinical, functional, and imaging characteristics of adults with CLM. METHODS: A retrospective study was carried out in adults with CLM followed up at our center. We assessed clinical characteristics, spirometry measures (FEV1, FVC, FEV1/FVC, and MMEF25-75), adult body plethysmography (TLC, RV, RV/TLC), and longitudinal volumetric quantification of CLM size on computed tomography (CT). RESULTS: Thirty patients with CLM were included (14 diagnosed prenatally, 16 referred). Seventeen (57%) underwent surgery at a median age of 4 years (interquartile range 0-24.5). Adult symptoms occurred in 17 (57%) patients, with 86% of episodes managed conservatively. Two pulmonary malignancies (pleuropulmonary blastoma and adenocarcinoma) were identified in referrals, aged 24 and 31 respectively. Childhood spirometry showed reduced mean z-scores for FEV1 (-1.1±1.6; p=0.02) and FEV1/FVC (-1.3±1.6; p=0.01), as well as scores below the lower limit of normal (LLN; z-score <-1.64) for MMEF25-75 (-1.7±1.4; p<0.001). In adulthood, mean z-scores remained negative for all indices, with FEV1 (-1.7±1.5; p<0.001) and MMEF25-75 (-1.8±1.3; p<0.001) averaging below the LLN, while body plethysmography outcomes were mixed. Longitudinal volumetric CT analysis revealed that lesion size increased in 8 patients, fluctuated in 2, and decreased in 6. CONCLUSION: Adults with CLM show persistent functional impairments and heterogeneous lesion progression on imaging. These findings mandate a standardized, multimodal surveillance protocol beyond childhood to proactively monitor for signs of late-onset disease progression.
Risk Factors and Microbiological Characteristics of Ventilator-Associated Pneumonia in a Tunisian Intensive Care Unit During the COVID-19 Pandemic.
Ben Fredj H, Sakhri S, Hafyene A … +3 more , Mtimet F, Abdeljaoued Y, Jebri A
Respir Med · 2026 Jul · PMID 42398840 · Publisher ↗
BACKGROUND: Ventilator-associated pneumonia (VAP) is a major intensive care unit (ICU) complication, particularly in North Africa where multidrug-resistant (MDR) organisms are frequent. This study aimed to determine risk...
BACKGROUND: Ventilator-associated pneumonia (VAP) is a major intensive care unit (ICU) complication, particularly in North Africa where multidrug-resistant (MDR) organisms are frequent. This study aimed to determine risk factors, microbiological patterns, and outcomes of VAP in a Tunisian tertiary ICU during the COVID-19 pandemic. METHODS: We conducted a retrospective observational study including 422 mechanically ventilated patients. VAP was defined using modified Johanson criteria. A multivariable logistic regression model was performed to identify independent risk factors for VAP development, in accordance with STROBE guidelines. Time-related outcomes were not included in the model to avoid temporal bias. RESULTS: The VAP incidence was 24.2% (6.2 per 1,000 ventilator-days), with a median onset of 8 days after intubation. Independent risk factors for VAP included polytrauma, intrahospital transport, diabetes, male sex, and age > 75 years. COVID-19 ARDS was associated with a lower adjusted risk of VAP, likely reflecting selection and competing risk biases during the pandemic. Microbiological analysis showed a strong predominance of Gram-negative bacilli. Overall, 59% of isolates were MDR, mainly Acinetobacter baumannii and Klebsiella pneumoniae. Prior antibiotic exposure was strongly associated with MDR infections. ICU mortality among VAP patients was 40%, and hospital mortality reached 44%. CONCLUSION: In this pandemic-era single-center ICU cohort, VAP was associated with high morbidity and mortality and a substantial burden of MDR Gram-negative pathogens. These results highlight the impact of ICU-specific risk factors and prior antibiotic exposure, and should be interpreted within the context of a COVID-19-dominated ICU, limiting generalizability to non-pandemic settings.
Impact of Therapeutic Hypothermia on Oxygen Demand and Respiratory Function in Post-Cardiac Arrest Patients: A Retrospective Cohort Study.
Cheng TJ, Lai YH, Liao JC … +2 more , Wu BR, Yeh Z
Respir Med · 2026 Jul · PMID 42392280 · Publisher ↗
OBJECTIVE: This study aimed to evaluate the effects of therapeutic hypothermia (TH) on oxygen demand, respiratory function, and overall clinical outcomes in post-cardiac arrest patients, specifically focusing on improvem...
OBJECTIVE: This study aimed to evaluate the effects of therapeutic hypothermia (TH) on oxygen demand, respiratory function, and overall clinical outcomes in post-cardiac arrest patients, specifically focusing on improvements in oxygenation, ventilatory parameters, and metabolic status. METHODS: A retrospective cohort study was conducted from January 1, 2018, to June 30, 2022, including patients who received therapeutic hypothermia after cardiac arrest. Initially, 146 patients with bilateral lower-lung infiltrates suggestive of pneumonia on chest radiographs were screened. After applying exclusion criteria-such as in-hospital death during hypothermia (n = 58), non-pneumonia cases (n = 3), use of ECMO (n = 2), missing data (n = 3), and uncommon ventilator modes (n = 2)-79 patients remained for final analysis. Key ventilator parameters, including FiO and minute ventilation (MV), were assessed over time. RESULTS: Of the 146 patients screened, 79 met the inclusion criteria. The PaO/FiO (P/F) ratio remained stable throughout the therapeutic hypothermia period, indicating no significant deterioration in pulmonary oxygenation. Conversely, lactate levels progressively decreased, reflecting improved systemic oxygenation. Both minute ventilation (MV) and oxygen demand declined over time, suggesting a more favorable oxygen supply-demand balance under the reduced metabolic conditions induced by hypothermia. CONCLUSION: Therapeutic hypothermia did not significantly alter pulmonary oxygenation, as evidenced by stable P/F ratios. However, it effectively reduced metabolic demand, cardiac output, and overall oxygen consumption, potentially improving tissue-level oxygenation and enhancing clinical outcomes, particularly in terms of survival and recovery. Further prospective studies are needed to clarify its impact on pulmonary circulation, long-term prognosis, and its role in optimizing post-cardiac arrest care strategies. TRIAL REGISTRATION: CMUH114-REC2-096(AR-1) ; date of registration: 2026-06-02.
The longitudinal decrease in exercise tolerance and disease progression in mild-to-moderate COPD.
Wan Q, Deng Z, Wu F … +19 more , Zhou K, Tang G, Huang S, Dai C, Lu L, Wu X, Cai G, Wu F, Wang X, Lin J, Xu B, Li S, Yang C, Chen S, Huang Y, Yu S, Zhou Y, Ran P, ECOPD Study Investigators
Respir Med · 2026 Jul · PMID 42392279 · Publisher ↗
INTRODUCTION: Exercise intolerance serves as a prognostic marker for poor respiratory outcomes in mild-to-moderate COPD. However, the longitudinal change in exercise tolerance and its association with disease progression...
INTRODUCTION: Exercise intolerance serves as a prognostic marker for poor respiratory outcomes in mild-to-moderate COPD. However, the longitudinal change in exercise tolerance and its association with disease progression remains unknown. To explore the association of longitudinal change in exercise tolerance with disease progression in mild-to-moderate COPD. METHODS: This community-based, prospective cohort study was conducted in China from 2019 to 2024. The participants completed baseline questionnaires, spirometry, chest computed tomography, and cardiopulmonary exercise testing (CPET), and underwent annual acute exacerbation assessment and spirometry over 3 years. Participants were categorized by the longitudinal change in peak oxygen uptake from baseline to 3 years into groups with non-declined or declined exercise tolerance. RESULTS: Overall, 213 patients with mild-to-moderate COPD who completed baseline and 3-year CPET were analyzed, including 131 (61.5%) with exercise tolerance decline. For every 5% longitudinal decrease in exercise tolerance, there was greater progression of air trapping (adjusted difference=0.18%/year, 95% CI 0.01-0.34, P = 0.033) and a faster decline in postbronchodilator FEV (adjusted difference=-4.2 mL/year, 95% CI -8.3 to -0.1, P = 0.044). Compared with the non-declined exercise tolerance group, the group with exercise tolerance decline demonstrated greater progression of emphysema (adjusted difference=0.40%/year, 95% CI 0.10-0.69, P = 0.008) and air trapping (adjusted difference=1.26%/year, 95% CI 0.41-1.84, P = 0.002). CONCLUSIONS: The longitudinal decrease in exercise tolerance over 3 years was associated with accelerated lung function decline and air trapping progression, suggesting it may be a marker associated with disease progression in mild-to-moderate COPD.
The implications of adopting the race-neutral spirometry equations in the detection of airway obstruction in Chilean children with asthma.
Rodríguez-Martínez CE, Rojas-Soto GE, Aguirre-Camposano V … +2 more , Sossa-Briceno MP, Mallol J
Respir Med · 2026 Jul · PMID 42392278 · Publisher ↗
OBJECTIVES: This study compared the performance of the GLI-2012 and GLI-2022 equations for detecting airway obstruction in Chilean asthmatic children. METHODS: This cross-sectional analytical study compared the predicted...
OBJECTIVES: This study compared the performance of the GLI-2012 and GLI-2022 equations for detecting airway obstruction in Chilean asthmatic children. METHODS: This cross-sectional analytical study compared the predicted values and z-scores for forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), and the FEV/FVC ratio, calculated using the GLI-2012 Caucasian and race-neutral GLI-2022 equations, in 885 Chilean children with asthma aged 6-16 years. Airway obstruction was defined as an FEV/FVC z-score of less than -1.64. Multivariable generalised estimating equations (GEE) logistic regression was used to identify the independent predictors of obstruction classification. This accounted for paired observations and adjusted for age, sex, and anthropometric covariates, including height-for-age and FVC z-scores. RESULTS: Switching from the GLI-2012 equations to the race-neutral GLI-2022 equations increased the prevalence of airway obstruction from 12.9% to 14.0% (p = 0.002). Multivariable GEE analysis revealed that the GLI-2022 model was an independent predictor of obstruction (OR: 1.10; 95% CI: 1.02-1.19; p = 0.014). Meanwhile, height-for-age was a significant protective factor (OR: 0.72; 95% CI: 0.59-0.89; p = 0.003), while higher FVC z-scores were associated with an increased likelihood of an obstructed result (OR: 1.41; 95% CI: 1.12-1.77; p = 0.003). CONCLUSIONS: Using the race-neutral GLI-2022 reference equations was associated with a higher detection of airway obstruction in Chilean children, resulting in unidirectional diagnostic reclassification. This transition is independent of sex but is significantly influenced by individual lung geometry and dysanapsis. These findings emphasise the importance of taking a nuanced, patient-specific clinical approach when implementing global reference standards.
Long-term outcomes of home mechanical ventilation in Duchenne Muscular Dystrophy - an observational study.
Benning L, Brunner TS, Mollet M … +4 more , Bradicich M, Bousraou Z, Ulrich S, Schwarz EI
Respir Med · 2026 Jul · PMID 42386012 · Publisher ↗
BACKGROUND AND METHODS: Home-mechanical-ventilation in Duchenne muscular dystrophy improves survival and quality of life. In this observational study in Duchenne muscular dystrophy patients, lung function and respiratory...
BACKGROUND AND METHODS: Home-mechanical-ventilation in Duchenne muscular dystrophy improves survival and quality of life. In this observational study in Duchenne muscular dystrophy patients, lung function and respiratory muscle strength at the time of ventilation-initiation and their change under home-mechanical-ventilation were investigated. Main outcomes of interest were age and pulmonary function at the time of ventilation-initiation. RESULTS: Age at start of nocturnal home-mechanical-ventilation was 19.8 ± 4.8 years (n = 80) and 23.8 ± 5.4 years when home-mechanical-ventilation was extended to daytime (63/80). 25/80 patients were ventilated via tracheostomy (8% initially, 92% switched after 86 ± 46 months of non-invasive ventilation). Forced vital capacity, maximal inspiratory pressure and sniff nasal pressure at the start of home-mechanical-ventilation were 21 ± 13% predicted, -26.9 ± 15.4 cmH2O, and -20.3 ± 11.7 cmH2O, respectively. Forced vital capacity was an independent negative predictor of sleep-hypoventilation, even after adjustment for body-mass-index and age, whereas inspiratory muscle strength measures were not. Starting home-mechanical-ventilation slowed the decline in forced vital capacity and inspiratory muscle strength. Median survival was 33 (28-39) years. CONCLUSIONS: In summary, indication of home-mechanical-ventilation can be expected at a median age of 20 (16-22) years and at a forced vital capacity of 18% (12-20) predicted in Duchenne muscular dystrophy. Initiation of home-mechanical-ventilation slows the decline in lung function.
CT-derived vascular parameters and bone mineral density in adults with cystic fibrosis.
Çınar C, Alev E, Mercancı Z … +3 more , Kanık KBK, Kanık A, Karakurt S
Respir Med · 2026 Jul · PMID 42386011 · Publisher ↗
BACKGROUND: Cystic fibrosis (CF) is a multisystem disorder in which reduced bone mineral density (BMD) is a common and clinically significant complication. While dual-energy X-ray absorptiometry (DEXA) is the standard di...
BACKGROUND: Cystic fibrosis (CF) is a multisystem disorder in which reduced bone mineral density (BMD) is a common and clinically significant complication. While dual-energy X-ray absorptiometry (DEXA) is the standard diagnostic method, imaging-derived parameters from routinely performed thoracic computed tomography (CT) may provide additional insight into systemic disease burden. This study aimed to investigate the association between CT-derived vascular metrics and BMD in adults with CF. METHODS: This retrospective observational study included adult CF patients who underwent dual-energy X-ray absorptiometry (DEXA) and thoracic CT between 2017 and 2023 at a tertiary referral center. Clinical variables, pulmonary function, hospitalization history, inflammatory markers, and CT-derived vascular measurements including pulmonary artery (PA) diameter, ascending aortic (Ao) diameter, and PA/Ao ratio were analyzed. Patients were categorized according to World Health Organization osteopenia criteria and a low BMD subgroup (T-score < -1.5). Receiver operating characteristic (ROC) analyses and multivariate logistic regression were performed to identify factors associated with low BMD. RESULTS: Seventy-four adult CF patients were included. Using the standard osteopenia threshold (T-score < -1.0), patients with low BMD had significantly lower FEV, lower body mass index, and higher CF-ABLE scores. In the low BMD subgroup (T-score < -1.5), patients were younger (p = 0.008), had smaller ascending aortic diameters (p = 0.005), higher PA/Ao ratios (p = 0.029), and more hospitalizations (p = 0.046). ROC analysis demonstrated moderate discriminatory performance for CT aortic diameter (AUC = 0.746) and age (AUC = 0.723). In multivariate analysis, younger age remained the only independent predictor of low BMD (OR 0.81, 95% CI 0.67-0.97, p = 0.025). CONCLUSION: CT-derived vascular parameters were associated with low BMD in adults with CF, particularly in patients with more advanced bone loss. These findings suggest that vascular metrics may reflect more advanced systemic disease involvement rather than early osteopenia. However, given the cross-sectional design, causality cannot be inferred. Prospective longitudinal studies are needed to validate the predictive value of these imaging markers and clarify the relationship between vascular alterations and bone health.
Effects of integrated inspiratory-expiratory muscle training within hybrid cardiac rehabilitation following cardiac surgery: A randomized controlled study.
Eksi BU, Cilbir CE, Ucgun H … +6 more , Ertan Harputlu O, Aslan GK, Ezelsoy M, Ugurlucan M, Sagbas LE, Akinci B
Respir Med · 2026 Jul · PMID 42386010 · Publisher ↗
BACKGROUND: Cardiac surgery may reduce pulmonary function, respiratory muscle strength, and functional capacity after surgery. Respiratory muscle training (RMT) is recommended in cardiac rehabilitation; however, evidence...
BACKGROUND: Cardiac surgery may reduce pulmonary function, respiratory muscle strength, and functional capacity after surgery. Respiratory muscle training (RMT) is recommended in cardiac rehabilitation; however, evidence regarding RMT within HCR remains limited. OBJECTIVE: To evaluate the effects of adding RMT to an HCR program following cardiac surgery in a randomized controlled trial. METHODS: In this randomized controlled trial, 20 patients were randomized to HCR (n = 10) or HCR + RMT (n = 10). Rehabilitation started in postoperative week 1 and continued for 8 weeks. Both groups received HCR, while the HCR + RMT group performed combined inspiratory and expiratory muscle training. Primary outcomes were pulmonary function, respiratory muscle strength, and 6-min walk distance. Secondary outcomes included quality of life, physical activity, usability, feasibility, and satisfaction. RESULTS: Twenty participants completed the study, with 100% retention and attendance in both groups and no adverse events. At postoperative week 1, respiratory and functional parameters declined in both groups. By week 8, 6-min walk distance increased by 49.5 m in the HCR group and 55.5 m in the HCR + RMT group. Duke Activity Status Index scores improved by 5.25 and 4.95 points, respectively, while Minnesota Living with Heart Failure Questionnaire scores decreased by 7-9 points. No significant between-group differences were found for any outcome (all p > 0.05). CONCLUSIONS: Adding RMT to HCR is feasible, safe, and well accepted. Both interventions improved respiratory function, respiratory muscle strength, functional capacity, physical activity, and quality of life. Although no additional short-term benefit was observed with RMT, it may be considered complementary to HCR programs. CLINICAL TRIAL REGISTRATION NUMBER: NCT06258681.
Prognostic and incremental value of the red cell distribution width-to-albumin ratio for in-hospital mortality in acute respiratory failure.
Delen LA, Aydın A, Dişli ZK
Respir Med · 2026 Jul · PMID 42386009 · Publisher ↗
BACKGROUND: Acute respiratory failure (ARF) is a life-threatening condition associated with substantial mortality in intensive care units. Biomarkers reflecting both inflammatory burden and nutritional status may enhance...
BACKGROUND: Acute respiratory failure (ARF) is a life-threatening condition associated with substantial mortality in intensive care units. Biomarkers reflecting both inflammatory burden and nutritional status may enhance prognostic accuracy beyond conventional clinical scores. This study evaluated the independent and incremental prognostic value of the red cell distribution width-to-albumin ratio (RAR) for predicting in-hospital mortality in patients with ARF. METHODS: In this retrospective cohort study, 1581 patients admitted to the intensive care unit with ARF between January 2023 and December 2025 were analyzed. Demographic characteristics, admission laboratory parameters, and APACHE II scores were recorded. Discriminatory performance was assessed using receiver operating characteristic (ROC) analysis. The incremental contribution of RAR beyond a baseline clinical model was evaluated using continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Internal validation was performed using bootstrap resampling. RESULTS: Overall, 450 patients (28.5%) died during hospitalization. RAR values were significantly higher among non-survivors compared with survivors (6.00 vs. 4.57; p < 0.001). The area under the curve for RAR in predicting mortality was 0.711 (95% CI: 0.68-0.74). In multivariable analysis, RAR remained independently associated with mortality (OR 1.176; 95% CI 1.107-1.250; p < 0.001). Similar findings were observed in Cox proportional hazards models and in sensitivity analyses using 28-day mortality. Addition of RAR to the baseline model was associated with improved risk classification (continuous NRI 0.384; p < 0.001) and discrimination (IDI 0.014; p < 0.001). CONCLUSIONS: RAR independently predicts in-hospital mortality in ARF and provides modest incremental prognostic value beyond conventional risk scores. Further external validation is warranted before routine clinical implementation.
Irisin in airway remodeling in COPD: Regulatory mechanisms from epithelial barrier to smooth muscle.
Yang X, Wang X
Respir Med · 2026 Jul · PMID 42386008 · Publisher ↗
This review synthesizes the emerging evidence positioning irisin, a myokine released during physical activity, as a critical molecular link in chronic obstructive pulmonary disease (COPD) airway remodeling. Clinically, i...
This review synthesizes the emerging evidence positioning irisin, a myokine released during physical activity, as a critical molecular link in chronic obstructive pulmonary disease (COPD) airway remodeling. Clinically, irisin deficiency is consistently observed in COPD and correlates with key features including reduced physical activity, respiratory muscle weakness, sarcopenia, emphysema severity, and exacerbation risk, supporting a hypothesis of a "muscle-lung crosstalk" axis. At the cellular level, irisin exerts direct protective effects on airway structural cells by preserving epithelial barrier integrity via anti-apoptotic and antioxidant mechanisms, while modulating airway smooth muscle tone, proliferation, and extracellular matrix dynamics. Mechanistically, these actions converge on core signaling networks centered on AMPK activation, coordinating downstream pathways such as PGC-1α-mediated mitochondrial regulation, mTOR-dependent autophagy, and SIRT1-driven anti-inflammatory cascades. Emerging layers of complexity involve non-coding RNAs, extracellular vesicles, integrin αVβ5 receptor signaling, and intracellular interactions like Enolase 1 (ENO1) ubiquitination. Collectively, these findings form an "exercise/pharmacology-irisin-airway structural cell-signaling pathway-airway remodeling" framework. Beyond irisin, other adipomyokines (leptin, adiponectin, BDNF, and erythropoietin) exhibit distinct-often opposing-inflammatory and immune profiles in COPD, underscoring a broader multi-hormone network. Future directions should focus on validating irisin as a clinical biomarker and exploring irisin-based therapeutic interventions, which represent a promising avenue for improving COPD management.
Lung ultrasound in interstitial lung disease: from bedside screening to prognostic integration and AI-assisted standardization.
Yang J, Lin Y, Bai J … +2 more , Zhu Z, Lian X
Respir Med · 2026 Jun · PMID 42379532 · Publisher ↗
Interstitial lung diseases (ILDs) require early recognition and longitudinal assessment, yet repeated high-resolution computed tomography (HRCT) is often limited by access, cost, and cumulative radiation exposure, partic...
Interstitial lung diseases (ILDs) require early recognition and longitudinal assessment, yet repeated high-resolution computed tomography (HRCT) is often limited by access, cost, and cumulative radiation exposure, particularly in connective tissue disease-associated ILD (CTD-ILD). Lung ultrasound (LUS) is a bedside, radiation-free, repeatable adjunct that primarily evaluates B-line burden and pleural line abnormalities. In this review, we summarize core sonographic signs and key diagnostic pitfalls, and synthesize the evidence for three clinical domains: screening, case finding and triage in high-risk populations, phenotype-relevant cues, and interval monitoring between HRCT examinations, ideally alongside pulmonary function tests. We further compare scanning protocols and scoring approaches, including B-line-dominant, pleural line-dominant, and composite frameworks, and outline practical strategies for harmonized acquisition, reproducible scoring, and structured reporting. We also review the emerging role of artificial intelligence (AI) in acquisition guidance, quality control, and feature quantification, while emphasizing important boundaries related to device variability, disease-spectrum shift, and limited specificity. Current evidence most strongly supports LUS as a complementary tool for screening, triage and bedside trend monitoring, particularly in CTD-ILD, whereas phenotype-oriented interpretation, progression-sensitive markers, and AI-enabled deployment remain developmental. Future priorities include multicentre harmonization of protocols and scoring, prospective validation of clinically meaningful change, and transparent external evaluation to support safe integration into multidisciplinary care pathways.
Pathophysiology of silenthypoxia in COVID-19: Truth and mystery.
Alsulami AS, Al-Kuraishy HM, Al-Gareeb AI … +3 more , Abdelnaby MA, Haggag MM, El-Saber Batiha G
Respir Med · 2026 Jun · PMID 42379531 · Publisher ↗
Coronavirus disease 2019 (COVID-19) is a highly infectious viral disease caused by the SARS-CoV-2. COVID-19 commonly leads to mild flu-like illness in most of cases. However, severe COVID-19-induced pneumonia and associa...
Coronavirus disease 2019 (COVID-19) is a highly infectious viral disease caused by the SARS-CoV-2. COVID-19 commonly leads to mild flu-like illness in most of cases. However, severe COVID-19-induced pneumonia and associated acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) may lead to ventilation-perfusion mismatch and the development of silent hypoxia. Silent hypoxemia is observed in critically COVID-19 patients without signs of subjective dyspnea that is often linked with poor clinical outcomes. Proposed mechanisms include impairment of peripheral carotid chemoreceptors, attenuation of the sensitivity of the respiratory center, and the development of acute vascular distress syndrome (AVDS). However, it should be noted that while AVDS is supported by imaging and pathological evidence, the roles of carotid body dysfunction and other proposed mechanisms remain incompletely validated and require further investigation. The pathophysiology of silent hypoxia in COVID-19 and other viral infections is a complex condition. Accordingly, this review aims to explain and discuss the pathophysiology of silent hypoxia, and its critical role in COVID-19.
Transformations within cystic fibrosis model of care in the era of CFTR modulators: a Scoping Review.
Gautiez R, Reix P, Poupon-Bourdy S … +5 more , Reynaud Q, Fayolle R, Cornec S, Durieu I, Haesebaert J
Respir Med · 2026 Jun · PMID 42379530 · Publisher ↗
BACKGROUND: Highly effective CFTR modulator therapies have substantially transformed the clinical course of cystic fibrosis (CF), raising questions regarding the organisation and delivery of CF care. However, how CF care...
BACKGROUND: Highly effective CFTR modulator therapies have substantially transformed the clinical course of cystic fibrosis (CF), raising questions regarding the organisation and delivery of CF care. However, how CF care models are adapting to this new therapeutic context remains unclear. METHODS: A scoping review was conducted to identify literature published from 2012 onwards addressing organisational changes and stakeholder needs related to CF care in the context of CFTR modulator therapies. We included empirical studies evaluating organisational interventions, opinion or position papers proposing adaptations of care organisation, and studies exploring the needs and perceptions of people with CF, families, and healthcare professionals. RESULTS: Nineteen publications were included, most originating from North America and Western Europe. The available literature suggests that organisational adaptations in CF care remain at an early stage and are primarily characterised by targeted or incremental changes rather than comprehensive redesign of care models. Telehealth and hybrid follow-up approaches were the most frequently described adaptations, alongside evolving multidisciplinary team roles and increasing interest in personalised care pathways. However, robust empirical evaluations of system-level organisational transformation remain limited. CONCLUSIONS: While highly effective CFTR modulators are reshaping the clinical landscape of CF, evidence supporting large-scale transformation of CF care organisation remains limited. Current findings suggest a gradual evolution toward more flexible and individualised care models, but further longitudinal and system-level evaluations are needed to guide evidence-based adaptation of CF care delivery.
Targeting the neutrophil-DPP-1-protease axis in airway disease: current evidence and future indications.
Pastorino L, Ferraris M, Robbiano M … +3 more , Staffiere C, Riccio AM, Braido F
Respir Med · 2026 Jun · PMID 42372954 · Publisher ↗
Neutrophils contribute to chronic airway diseases with variable pathogenic relevance across conditions. In bronchiectasis, persistent airway neutrophilia and sustained activity of neutrophil serine proteases (NSPs) - neu...
Neutrophils contribute to chronic airway diseases with variable pathogenic relevance across conditions. In bronchiectasis, persistent airway neutrophilia and sustained activity of neutrophil serine proteases (NSPs) - neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG) - directly drive structural damage and exacerbations. In Chronic Obstructive Pulmonary Disease (COPD), neutrophils participate in parenchymal destruction and systemic inflammation within a broader network of oxidative and immune dysregulation. In T2-low asthma, neutrophilic inflammation is heterogeneous and context-dependent, suggesting a less uniform contribution of NSP-mediated injury. Therapeutic strategies targeting neutrophils downstream have yielded limited clinical success: selective NE inhibitors and C-X-C motif chemokine receptor 2 (CXCR2) antagonists reduced protease activity or neutrophil recruitment but failed to produce consistent improvements in lung function or exacerbation rates. These evidences reflect redundancy among NSPs, compensatory inflammatory pathways, and the presence of pre-activated circulating neutrophils whose proteolytic potential is already established before tissue recruitment. This has shifted attention upstream to the neutrophil-DPP-1-protease axis. Dipeptidyl peptidase-1 (DPP-1) activates NSPs during neutrophil maturation in the bone marrow; its inhibition reduces the protease load of circulating neutrophils without broadly suppressing innate immunity. In bronchiectasis, DPP-1 inhibitors have demonstrated clinically meaningful reductions in exacerbations and airway NSP activity, providing proof of concept for disease modification. In COPD, this strategy is biologically compelling, particularly in neutrophil-predominant phenotypes, but requires dedicated clinical validation. In asthma, any therapeutic role is likely restricted to highly selected T2-low, neutrophil-driven subsets. Future progress will depend on biomarker-guided stratification to define where modulation of the neutrophil-NSP axis can meaningfully alter disease trajectory.
The lung microbiome in hematopoietic stem cell transplantation: immune interactions, clinical consequences, and emerging interventions.
Hajjar C, Saint-Criq V, Thomas M … +3 more , Butel MJ, Bazarbachi A, Abifadel M
Respir Med · 2026 Jun · PMID 42364737 · Publisher ↗
Hematopoietic stem cell transplantation (HSCT) offers curative potential for hematologic malignancies and immune disorders, yet pulmonary complications remain major contributors to non-relapse morbidity and mortality. Tr...
Hematopoietic stem cell transplantation (HSCT) offers curative potential for hematologic malignancies and immune disorders, yet pulmonary complications remain major contributors to non-relapse morbidity and mortality. Traditionally attributed to immune suppression and graft-versus-host disease (GvHD), these complications are increasingly recognized to involve disruption of pulmonary microbial communities. A growing body of clinical and experimental evidence indicates that HSCT-associated perturbations in the lung microbiome, driven by conditioning, antimicrobials, immune injury, and infection, are associated with distinct post-transplant pulmonary phenotypes and, in some cohorts, with mortality risk. Whether these microbial shifts represent causal contributors to lung injury or contextual biomarkers of immune vulnerability remains unresolved, and this distinction carries direct implications for microbiome-targeted intervention. Dysbiotic shifts in the lung have been associated with both infectious and non-infectious complications, including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and fibrotic lung disease. Gut-lung microbial crosstalk may amplify or reflect systemic immune dysfunction, though the directionality of this relationship remains incompletely characterized. Multi-omics approaches, integrating metagenomics, metatranscriptomics, and metabolomics, are beginning to define the host-microbiome interaction signatures that distinguish injury subtypes and predict outcomes. This review synthesizes mechanistic insights into lung microbiome-immune interactions after HSCT, critically appraises the methodological constraints on the current evidence base, and evaluates microbiome-based interventions, including fecal microbiota transplantation, inhaled postbiotics, and precision antimicrobials, as candidate strategies for respiratory protection in transplant recipients, while acknowledging that prospective interventional evidence in this population remains limited.
GLP-1 receptor agonists in obstructive sleep apnea: A propensity score-matched real-world analysis.
Rai P, Bathla G, Praveen N … +13 more , Chen HA, Salim HA, Azzam AY, Essibayi MA, Altschul DJ, Dmytriw AA, Yedavalli VS, Latifi S, Malhotra A, Colasurdo M, Gandhi D, Sharma S, Lakhani DA
Respir Med · 2026 Jun · PMID 42362122 · Publisher ↗
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1As) confer cerebrovascular benefits in diabetes and obesity, but their long-term effects in obstructive sleep apnea (OSA), which is frequently associated with o...
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1As) confer cerebrovascular benefits in diabetes and obesity, but their long-term effects in obstructive sleep apnea (OSA), which is frequently associated with obesity and linked to poor cerebrovascular outcomes, remain unclear. METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network between January 1st 2016 to December 31st 2025. Adults with OSA were identified; exposure was initiation of a GLP-1A within 6 months before up to 1 month after OSA diagnosis. Propensity score matching was performed 1:1. Outcomes were assessed at 1, 3, and 5 years and included ischemic stroke, intracranial hemorrhage, emergency department visits, inpatient hospitalizations, and all-cause mortality. Kaplan-Meier analyses and Cox proportional hazards models were used. CPAP-restricted and tirzepatide-specific subgroup analyses were also performed. RESULTS: After matching, 438,844 patients were included in each cohort. Across 1-, 3-, and 5-year follow-up, GLP-1A exposure was associated with lower hazards of ischemic stroke (HRs, 0.75, 0.83, and 0.87), intracranial hemorrhage (HRs, 0.44, 0.56, and 0.61), emergency department visits (HRs, 0.77, 0.86, and 0.87), inpatient hospitalizations (HRs, 0.59, 0.67, and 0.69), and all-cause mortality (HRs, 0.38, 0.49, and 0.54; all p < 0.001). Associations were directionally consistent in CPAP-restricted and tirzepatide-specific subgroup analyses. CONCLUSIONS: In this large real-world cohort of patients with OSA, GLP-1A exposure was associated with lower hazards of cerebrovascular events, healthcare utilization, and all-cause mortality across 1-, 3-, and 5-year follow-up. These findings are hypothesis-generating and require validation in prospective studies evaluating incretin-based therapies as potential adjuncts to standard OSA management.
The hidden burden of overlap syndrome: Sleep quality and functional impairment in chronic obstructive pulmonary disease.
Camargo PF, Back GD, Carvalho LCS … +5 more , Arêas GPT, Goulart CDL, Anjolim LF, Lourencetti LR, Borghi-Silva A
Respir Med · 2026 Jun · PMID 42362121 · Publisher ↗
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with reduced functional capacity and a high prevalence of sleep-related disturbances. However, the relationship between sleep-related disturbances an...
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with reduced functional capacity and a high prevalence of sleep-related disturbances. However, the relationship between sleep-related disturbances and functional capacity remains incompletely understood. OBJECTIVE: To investigate the associations between COPD severity, sleep quality, nocturnal respiratory disturbances, and functional capacity assessed by the 6-min walk test (6MWT). METHODS: Eighty clinically stable patients with COPD underwent spirometry, home sleep monitoring, Pittsburgh Sleep Quality Index (PSQI), and 6MWT. Correlation and multiple linear regression analyses were performed. RESULTS: Patients with more severe disease exhibited higher apnea-hypopnea index values, lower mean SpO, and longer periods with SpO<90% (p = 0.001). Poorer sleep quality, higher apnea-hypopnea index, and greater nocturnal hypoxaemia were associated with shorter 6MWT distance. In multiple regression analyses, FEV and dyspnoea (mMRC) were the strongest predictors of functional capacity, while PSQI score, apnea-hypopnea index, and time spent with SpO<90% remained independently associated with walking distance. CONCLUSION: Increasing COPD severity was associated with poorer sleep quality, greater nocturnal oxygen desaturation, and lower functional capacity. Sleep-related variables were independently associated with 6MWT performance, suggesting that sleep assessment may provide complementary information in the evaluation of patients with COPD.
Quantitative CT-Derived extrapulmonary body composition and the risk of acute exacerbations in COPD: A prospective cohort study.
Miao C, Feng S, Wang F … +7 more , Yang Y, Chen Z, Li X, Zhou Z, Liu F, Chen R, Liang Z
Respir Med · 2026 Jun · PMID 42362120 · Publisher ↗
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently accompanied by systemic manifestations, including muscle wasting, osteoporosis, and cardiovascular disease. However, the associations between extrapu...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently accompanied by systemic manifestations, including muscle wasting, osteoporosis, and cardiovascular disease. However, the associations between extrapulmonary CT features and acute exacerbation (AE) risk remain incompletely understood. We investigated whether chest CT-derived measures of body composition, bone mineral density (BMD), and coronary artery calcification (CAC) are associated with AE risk and frequency in COPD. METHODS: In this prospective observational cohort study, 306 patients with COPD and 83 healthy controls were enrolled. Quantitative chest CT was used to assess pectoralis muscle area (PMA), subcutaneous adipose tissue (SAT), thoracic vertebral BMD, and CAC. COPD patients were categorized according to the occurrence and frequency of AEs within one and two years. Group comparisons were performed using nonparametric and categorical statistical tests. RESULTS: Compared with controls, patients with COPD had significantly lower PMA, SAT, and BMD (all p < 0.001), while CAC did not differ. Within one year, patients with AEs showed lower BMD than those without AEs (p = 0.032). Frequent exacerbators had reduced PMA and altered left circumflex artery calcification indices (p < 0.05). Over two years, patients with AEs exhibited greater left circumflex and total coronary calcification (p < 0.05). CONCLUSION: CT-derived muscle mass, BMD, and coronary calcification are associated with AE risk and frequency in COPD, supporting the clinical relevance of extrapulmonary CT markers for exacerbation risk stratification.
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