Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.

Background:Non-invasive ventilation (NIV) is recommended as the first-line treatment for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by decompensated hypercapnic acute respiratory failure (ARF). High-flow nasal cannula oxygen therapy (HFNO), given its superior tolerance and patient adherence, has emerged as a promising alternative non-invasive respiratory support modality applicable across a wider range of clinical scenarios. This study aimed to investigate the neurophysiological effects of NIV and HFNO in AECOPD patients with hypercapnic ARF. Methods:A prospective, randomised, crossover trial involving 10 AECOPD patients with decompensated hypercapnic ARF was conducted. Each patient underwent 30 min of treatment with both NIV and HFNO, with the neural respiratory drive (NRD) measured via a multi-pair oesophageal electrode catheter. Results:NIV significantly improved neuro-ventilatory coupling compared with HFNO (treatment difference: 1.73 L/%, 95% CI: 0.95 to 2.51 L/%, p = 0.001). Both HFNO and NIV enhanced NRD efficiency relative to conventional oxygen therapy (COT). Furthermore, NIV led to more pronounced improvements in inspiratory workload, respiratory muscle contraction, and work of breathing-evidenced by reductions in Peso, Pdi, PTPdi/breath, and PTPdi/min-compared with both COT and HFNO. HFNO also demonstrated physiological benefits over COT, with the unexpected exception of the neuro-mechanical efficiency and PTPdi/breath. Conclusion:In AECOPD patients with decompensated hypercapnic ARF, NIV significantly enhances NRD efficiency and reduces respiratory workload and related respiratory mechanics. HFNO, while less effective than NIV, still confers measurable physiological benefits and may serve as a viable alternative in resource-limited settings or those who are intolerant to NIV, potentially more appropriate for patients with less severe respiratory failure. Trial registration:ClinicalTrials.gov, NCT04212182. Registered 23 December 2019, https://clinicaltrials.gov/study/NCT04212182.

Galectin-7, a β-galactoside-binding lectin involved in inflammation, immune regulation, and apoptosis, has been implicated in the development and progression of various lung diseases. Inflammation, immune dysregulation, and epithelial cell apoptosis are key pathophysiological mechanisms underlying chronic obstructive pulmonary disease (COPD). However, the clinical significance of galectin-7 in COPD remains unclear. This study aimed to investigate the association between sputum galectin-7 levels and the clinical characteristics and prognosis of patients with COPD. In this prospective study, 150 patients with stable COPD and 50 healthy controls were enrolled. Demographic data, clinical parameters, and sputum samples were collected. Baseline galectin-7 concentrations in sputum supernatants were measured using an enzyme-linked immunosorbent assay (ELISA). Patients with COPD were followed for one year to document acute exacerbation events. Among COPD patients, Spearman correlation analysis and multivariable linear regression were performed to examine the associations between galectin-7 levels and clinical parameters or inflammatory markers, adjusting for sex, age, smoking status, and body mass index (BMI). Multivariable Poisson regression and logistic regression models were further applied to assess the relationship between galectin-7 levels and acute exacerbations within one year, with adjustment for the number of exacerbations in the previous year, sex, age, smoking status, BMI, and post-bronchodilator FEV1

BACKGROUND AND OBJECTIVE:Mixed granulocytic asthma (MGA) is clinically characterized by poor responsiveness to corticosteroid and a high predisposition of refractory asthma. While emerging evidence has implicated S100A8/A9 in the pathogenesis of asthma, its specific role in MGA remains unexplored. Therefore, this study aimed to investigate the role of S100A8/A9 signaling in Toluene diisocyanate (TDI)-induced asthma. METHODS:A murine model of TDI-induced MGA was established. Asthmatic mice were treated with S100A8/A9 specific inhibitors ABR-25757 (0.5 mg/kg) or ABR-238901 (20 mg/kg), respectively. Bronchoalveolar lavage fluid (BALF) and lungs tissues were collected for subsequent analysis. RESULTS:Increased S100A8/A9 expression was observed in the airway mucosa of asthmatic subjects. TDI exposure upregulated S100A8/A9 expression in the inflammatory cells infiltrating the periairway region and in bronchial epithelial cells, accompanied by increased airway hyperresponsiveness (AHR), mixed granulocytic inflammation, significant airway smooth muscle (ASM) thickening and extensive collagen deposition. All these pathological responses were markedly attenuated by treatment with ABR-25757 or ABR-238901. Additionally, TDI sensitization and challenge increased expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), toll-like receptor 4 (TLR4) and receptor for advanced glycation end-product (RAGE), as well as elevated BALF levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Notably, the upregulated expression of ICAM-1, VCAM-1, TLR4, RAGE and IL-6 were recovered by ABR-25757 or ABR-238901. CONCLUSION:Blockade of S100A8/A9 with specific inhibitors effectively suppressed the development of TDI-induced asthma, suggesting that S100A8/A9-targeted therapy holds potential as a clinical intervention for patients with MGA.

Analysis of proteins and other molecular components in induced sputum provides critical insights for the diagnosis, pathological assessment, and therapeutic monitoring of respiratory diseases. In this study, we collected three distinct types of induced sputum samples from patients with chronic obstructive pulmonary disease (COPD) and subjected them to proteomic and phosphoproteomic analysis using three different enzymatic digestion methods. We found that raw sputum samples yielded a higher number of uniquely identified proteins and phosphoproteins (1313 proteins and 1603 phosphorylation sites, corresponding to 782 phosphoproteins) and provided a more comprehensive characterization of COPD pathology. Furthermore, compared to in-gel digestion and in-solution digestion, the filter-aided sample preparation method increased protein identification by approximately 30% and yielded the highest number of unique protein identifications. Our study is the first to demonstrate that raw induced sputum can serve as a viable alternative source for liquid biopsy in respiratory diseases. We have also established the first methodological framework and dataset for proteomic and phosphoproteomic analysis of raw induced sputum, generating a preliminary map of the COPD sputum proteome and phosphoproteome. This novel proteomic and phosphoproteomic approach has untangled biologically relevant pathways in respiratory physiology, highlighting potential avenues for future research. Significance In this study, we aimed to investigate the feasibility of establishing and evaluating proteomic research methods using sputum samples from patients with chronic obstructive pulmonary disease (COPD). The ultimate goal was to develop analytical approaches suitable for sputum proteomics and phosphoproteomics and to preliminarily map the sputum proteome and phosphoproteome in COPD. It was found that raw sputum samples more comprehensively reflect the disease characteristics of COPD and are therefore more suitable for proteomic and phosphoproteomic studies of COPD. Among three mainstream enzymatic digestion methods, the Filter-Aided Sample Preparation (FASP) method demonstrated superior identification rates and was deemed most suitable for processing raw sputum samples. Furthermore, this study reports for the first time a draft map of the proteome and phosphoproteome of COPD sputum. This research provides valuable insights into sputum proteomic analysis and offers a useful resource for the study of respiratory diseases.

Background:Although dual bronchodilators represent the cornerstone of pharmacological therapy for chronic obstructive pulmonary disease (COPD), few affordable generic products are available worldwide. This study aimed to evaluate the clinical equivalence between TQC3403 [the first generic umeclidinium/vilanterol (UMEC/VI) dry powder inhaler (DPI)] and ANORO®. Methods:This multicenter, randomized, open-label, phase 3 equivalence trial was conducted at 56 centers in China. Eligible patients with moderate-to-severe COPD were randomized in a 1:1 ratio to receive either TQC3403 or ANORO® for 24 weeks. The primary efficacy endpoint was the change in trough forced expiratory volume in 1 second (FEV1) from baseline to week 24, with the equivalence interval set at ±70 mL. A mixed-effects model for repeated measures (MMRM) was used to evaluate the primary efficacy endpoint, presented as least squares mean (LSM) difference and its 95% confidence interval (CI). Secondary efficacy endpoints included peak FEV1 on day 1 and at week 24, trough FEV1 at weeks 4, 8, 12, and 18, COPD Assessment Test (CAT) score at week 24, incidence of moderate-to-severe acute exacerbations of COPD (AECOPD), average use of rescue medication, and percentage of days without rescue medication use. Safety outcomes included adverse events (AEs), treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs). Results:A total of 414 patients were enrolled, with 207 in each group. Baseline demographic and clinical characteristics of the two groups were similar. The LSM difference in the change in trough FEV1 from baseline to week 24 was 16 mL (95% CI: -30 to 62; P=0.49), entirely within the equivalence interval. The LSM differences in the change in peak FEV1 within 3 hours post-administration on day 1 and at week 24 were 8 mL (95% CI: -22 to 38; P>0.05) and 23 mL (95% CI: -29 to 74; P>0.05). The mean changes in CAT score were -4.1±5.91 in TQC3403 group and -4.1±5.15 in generic ANORO® group (P=0.97). The incidence of moderate-to-severe AECOPD was 4.35% in TQC3403 group and 2.42% in ANORO® group (P=0.28). Safety and tolerability profile was comparable between two groups. Conclusions:TQC3403 demonstrated clinical equivalence to ANORO® with respect to efficacy, safety, and tolerability in patients with COPD, supporting its clinical use as an effective and well-tolerated alternative for this population. Trial registration:The clinical research was registered at Chinese Clinical Trial Register (Ref: ChiCTR2600120078).

Background Chronic obstructive pulmonary disease (COPD) remains a major global health burden and is currently the third leading cause of death worldwide. Acute exacerbations accelerate disease progression and contribute substantially to mortality, underscoring the urgent need for reliable prognostic biomarkers. The endothelial activation and stress index (EASIX), a composite indicator of endothelial dysfunction, has demonstrated prognostic utility across diverse critical illnesses. However, its association with clinical outcomes in critically ill patients with COPD has not been clearly established. Methods In this retrospective cohort study, data of critically ill patients with COPD were extracted from the Medical Information Mart for Intensive Care (MIMIC) database. Participants were stratified into tertiles based on EASIX values, and intergroup differences in clinical characteristics were analyzed. The relationship between EASIX and 28-day all-cause mortality was examined using Kaplan-Meier survival analysis, Cox proportional hazards regression, and restricted cubic spline modeling. The Boruta algorithm was applied to assess the relative importance of candidate predictors, and prognostic models were subsequently developed using six machine learning algorithms. Results A total of 4,590 patients met the inclusion criteria. The incidence of 28-day ICU mortality increased progressively across higher EASIX tertiles (p < 0.001). EASIX was independently associated with 28-day ICU all-cause mortality, with both unadjusted and fully adjusted Cox models confirming this relationship (unadjusted HR = 1.21, p < 0.001; adjusted HR = 1.082, p < 0.001). Subgroup analyses demonstrated that the association between elevated EASIX and mortality risk remained consistent across demographic and comorbidity categories (p for interaction > 0.05 for all). The Boruta algorithm identified EASIX as one of the most important predictors of 28-day mortality. Among the six machine learning models evaluated, the XGBoost algorithm yielded the highest discriminative (AUC = 0.823), calibration and clinical application. Conclusions EASIX serves as an independent prognostic marker for 28-day all-cause mortality in critically ill COPD patients. Furthermore, the EASIX-based machine learning model demonstrated strong predictive accuracy, supporting its potential as a valuable clinical tool or early risk stratification and decision-making in intensive care settings.

Purpose:Patients with chronic obstructive pulmonary disease (COPD) with a history of frequent exacerbations have a high disease burden and poor progression, demanding optimized management. This study aimed to evaluate the real-world clinical situation, adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations, and the associated factors. Patients and Methods:We conducted a cross-sectional analysis of baseline data from the national multi-center Quality Improvement Program, which enrolled 1055 COPD patients with a high exacerbation risk from 40 hospitals across five geographic regions in China (NCT05638646). Patient characteristics, disease burden, management patterns and the associated factors were analyzed. Results:The study population had a mean age of 66.2 years, and 85.6% were male. Most patients had substantial disease burden, with 43.3% classified as GOLD stages 3-4 and 93.6% categorized into GOLD group E. In previous 12 months, 39.0% and 67.2% of these patients experienced at least one moderate or severe exacerbation, respectively. Overall, 75.1% received maintenance therapy using long-acting bronchodilators, but only 17.7% were receiving maintenance therapy consistent with the GOLD recommendations for initial treatment. Among patients receiving inhaled therapy, 70.9% initiated maintenance therapy within one month after diagnosis, whereas the self-reported good compliance was only 47.3%. Despite most patients received inhalation technique checks and education, only 61.9% can use the inhalation device appropriately, as evaluated by research team. Hospital level, hospital region, availability of blood eosinophil counts, and disease severity were significantly associated with the management patterns. Conclusion:COPD patients with a high exacerbation risk in China had a substantial disease burden and important gaps between real-world management patterns and GOLD recommendations. These findings suggest opportunities to improve guideline implementation, particularly in secondary and county-based hospitals. Future studies should evaluate whether targeted quality improvement interventions can improve patient outcomes. Trial Registration Number:NCT05638646.

Eosinophilic granulomatosis with polyangiitis (EGPA) and severe eosinophilic asthma (SEA) share a Type 2 (T2) inflammatory signature but exhibit distinct pathophysiology. We hypothesized that EGPA involves additional inflammatory mechanisms, beyond T2 immunity, that drive its systemic manifestations and treatment resistance. Using single-cell RNA sequencing, we identify interferon (IFN-I)-driven inflammation in EGPA, in contrast to TNF predominant pathway activation in SEA. IL1B+MX1+ neutrophils in EGPA express IFN-stimulated genes and promote tertiary lymphoid structure formation with autoantibody production. In addition, other IFN-activated granulocytes, including APOC1+ eosinophils, SCN7A+ mast cells, and basophils, further contribute to immune dysregulation in EGPA, unlike TNF activated granulocytes in SEA. Longitudinal single-cell analysis of EGPA reveals an IGF1+ macrophage population linked to EGPA relapse. In animal models of both conditions, IGF1 blockade attenuates T2 inflammation, mucin production, and goblet cell hyperplasia, highlighting IGF1 as a possible therapeutic target in T2 inflammation disease. There are similarities in airway inflammatory endotype between eosinophilic granulomatosis with polyangiitis (EGPA) and type 2 eosinophilic asthma. Here, the authors perform single-cell transcriptomics to compare EGPA with severe eosinophilic asthma and find differences in the innate immune cell populations and use mouse models to characterise the function and phenotype of these cells.

Background: Pneumonia is a common acute respiratory infection that contributes to significant mortality and morbidity worldwide. The disruption of the airway microbiome in respiratory infection has been extensively reported. However, whether the changes in respiratory tract microbial communities during pneumonia were related to disease severity remains elusive. Herein, we aimed to investigate the correlation between the changes in airway microbiome and immune response in pneumonia patients. Methods: We performed metagenomic and metatranscriptomic sequencing on immunocompetent (ICO) and immunocompromised host (ICH) with pneumonia using bronchoalveolar lavage fluid (BALF), blood, sputum, and swab samples. Results: Compared to ICO patients with pneumonia, ICH patients had higher Pneumonia Severity Index (PSI) score. BALF metagenomic and metatranscriptomic sequencing showed higher microbial diversity in ICH patients, while ICH patients exhibited lower microbial diversity in sputum samples. Additionally, pneumonia patients with different PSI scores exhibited different microbial communities. Relative abundance of Human Gammaherpesvirus 4 (EBV) was positively correlated with PSI score. For ICH patients, BALF metatranscriptomic sequencing found 183 up-regulated genes and 85 down-regulated genes in EBV-detected group compared with EBV not-detected group, while there was no significant difference in ICO patients, indicating that EBV might be reactivated in ICH patients, while EBV might be latent in ICO patients. In ICH patients, we observed significant down-regulation of immune related genes and interferon stimulated genes in EBV-detected group compared to the not-detected group, including CSF1R, CXCR6, IL10, IL16, and TNFRSF25. Co-occurrence network analysis found positive correlations between EBV and Citrobacter freundii or Campylobacter concisus, indicating that synergistic effects on exacerbating the severity of pneumonia might exist between EBV and these two microbes. Conclusion: EBV might be considered as a microbial signature for disease severity, which could regulate immune-related signaling pathways. Notably, we unravel that EBV presence might inhibit the immune response of hosts, reduce anti-inflammatory responses, and increase the possibilities of infections caused by other pathogens, exacerbating the pneumonia severity.

PURPOSE:SARS-CoV-2's persistent circulation and evolution necessitate development of antiviral drugs. This first-in-human Phase I study aimed to evaluate the safety, tolerability, pharmacokinetics (PK), and food effect (FE) of SAL0133, an orally bioavailable 3-chymotrypsin-like protease (3CLpro) inhibitor, in healthy participants through single ascending dose (SAD) and multiple ascending dose (MAD) parts. METHODS:Both SAD and MAD parts were randomized, double-blind, and placebo-controlled. The SAD part included 6 dose cohorts: 50 mg (fasted), 150 mg (fasted), 300 mg (fasted); and 150 mg (fed), 300 mg (fed), 600 mg (fed). The MAD part consisted of 3 dose cohorts: 150 mg (fasted); and 150 mg (fed), 300 mg (fed), with once-daily dosing for 7 days. Participants were randomized (6:2) to receive SAL0133 or placebo. FE evaluation was integrated into both parts. Safety and tolerability were assessed throughout the study. PK parameters were analyzed using non-compartmental methods, with dose proportionality evaluated using a confidence interval (CI)-based approach. Food effects were assessed by calculating 90% CIs for geometric least squares mean ratios of ln-transformed PK parameters. FINDINGS:SAL0133 was well tolerated. All treatment-emergent adverse events were mild except one grade 2 increased blood triglycerides. No dose-related adverse events were detected. Following a single oral administration, the median time to maximum concentration (Tmax) ranged from 3 to 6 hours, which was slightly delayed by food ingestion. Absorption saturation was reached at a single 150 mg dose under fasted conditions, while dosing after a high-fat meal significantly increased plasma maximum concentration (Cmax) by 1.89- and 3.42-fold and the area under the curve from time zero to infinity (AUCinf) by 1.45- and 3.78-fold at the 150 and 300 mg dose levels, respectively. Over the 50-150 mg dose range under fasted conditions, Cmax exhibited non-dose-proportionality, and AUC dose proportionality was inconclusive; over the 150-600 mg dose range under fed conditions, dose proportionality was also inconclusive for both AUC and Cmax, which may be partially attributable to absorptive saturation and the limited dose range under each dietary setting. Mean elimination half-lives (T1/2) ranged from 10.67 to 21.54 hours. Following multiple administrations, steady-state plasma concentrations were achieved by day 4. Under fed conditions, Cmax and AUC over the dosing interval (AUCtau) increased by approximately 1.7-fold at steady state as the dose doubled. IMPLICATIONS:Safety and PK results support once-daily administration without CYP3A4 inhibitor co-administration. Food significantly enhances its bioavailability, suggesting that dietary conditions require strict control while dosing.

Airway mucus overproduction (predominantly MUC5AC) is a well-recognized pathogenic feature in asthma, but the upstream regulatory mechanisms were enigmatic. Emerging evidence has implied the crucial role for transient receptor potential canonical channel 5 (TRPC5) in the pathogenesis of allergic diseases. Yet, the specific role of TRPC5 in asthma still remains unclear. Thus, this study was aimed to explore the functional role of TRPC5 in toluene diisocyanate (TDI)-induced mixed granulocytic asthma and to delineate the mechanisms by which TRPC5 regulate MUC5AC secretion. Bronchoalveolar lavage fluid (BALF) and mucosal biopsy samples were collected from asthmatic subjects and control. Using a murine model of TDI-induced asthma, we gave the asthmatic mice selective TRPC5 inhibitors ML204, AC1903 or an NLRP3 inhibitor, MCC950. In vitro experiments were performed in a human airway epithelial cell line BEAS-2B. BALF levels of MUC5AC were significantly increased in the recruited asthmatic patients, as well as the levels of HMGB1, and a positive correlation was observed between the two. Expression of TRPC5 was elevated in the airway epithelium of asthmatics when compared to the control. In mice, TDI exposure raised the expression of TRPC5. Blocking TRPC5 with either ML204 or AC1903 dramatically attenuated TDI-induced airway hyperresponsiveness (AHR), airway inflammation and remodeling. Additionally, both antagonists led to inhibited activation of NLRP3 inflammasome and muc5ac secretion in TDI-exposed mice. While pharmacological inhibition of NLRP3 inflammasome suppressed TDI-induced muc5ac secretion. In vitro, TDI induced increased expression of MUC5AC, NLRP3 and TRPC5 in BEAS-2B. Silence of either trpc5 or nlrp3 effectively inhibited MUC5AC hypersecretion in airway epithelium induced by TDI. Besides, TRPC5 agonist (Riluzole) promoted MUC5AC overproduction in airway epithelial cells, which could be suppressed by nlrp3 siRNA. TRPC5 contributes to TDI-induced asthma, and mediates airway epithelial muc5ac hypersecretion by partially activating NLRP3 inflammasome. TRPC5 Mediates MUC5AC Secretion via NLRP3 Inflammasome in Toluene Diisocyanate-Induced Asthma

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.

Pulmonary vascular diseases may affect arteries and veins through different physiological mechanisms, necessitating separate assessment of the two vascular trees. However, manual analysis of chest computed tomography (CT) images is time-consuming, subjective, and challenging to scale for clinical studies. To address this, we propose a novel Human-in-the-Loop (HITL) framework for annotation and model training to develop an automated pulmonary artery-vein segmentation model. Through three iterative HITL rounds, we constructed 30 gold-standard annotated datasets and trained three deep learning models. The optimal model achieved strong performance, with a Dice coefficient of 86.2%, IoU of 75.7%, sensitivity of 85.8%, and precision of 88.1%. This model was then applied to segment pulmonary arteries and veins in CT scans from patients with chronic obstructive pulmonary disease (COPD). Quantitative analysis revealed that, as COPD progresses, the volume and surface area of both pulmonary arteries and veins increase. Moreover, small vessel truncation becomes more pronounced, with small arteries showing greater structural loss than veins. These findings suggest distinct vascular remodeling patterns between arterial and venous trees across different disease stages. Our HITL-based framework not only enhances annotation efficiency but also supports the development of robust segmentation models. This approach holds promise for broader applications in medical image analysis and provides a valuable tool for characterizing vascular changes in COPD, contributing to improved diagnosis and patient management.

Noninvasive evaluation of partial pressure of carbon dioxide (PCO2) is clinically important for screening and monitoring of hypercapnia, especially in patients with chronic obstructive pulmonary disease (COPD). However, the comparative accuracy of end-tidal PCO2 (PetCO2) and transcutaneous PCO2 (PtcCO2) monitoring in COPD remains uncertain. This study aimed to evaluate the agreement between PetCO2 obtained by using modified method of prolonged expiration with an integrated calculation algorithm (PetCO2-PA) and PtcCO2 with arterial PCO2 (PaCO2) in patients with COPD. In this single-center study, 83 patients with COPD (48 at stable phase and 35 during acute exacerbation) underwent arterial blood gas (ABG) analysis followed with simultaneous measurement of PetCO2-PA and PtcCO2. Agreement between different measurements was assessed using Bland–Altman analysis (bias and limits of agreement (LOA)), and intraclass correlation coefficients. The receiver operating characteristic curve was used for evaluation of ability to detect hypercapnia, defined as PaCO2 ≥ 45 mmHg and ≥ 50 mmHg. Bland–Altman analysis revealed a small bias of − 1.7 mmHg but a relatively wide LOA of − 8.6 to 5.1 for PtcCO2 and − 2.4 mmHg (LOA: − 9.9 to 5.1) for PetCO2-PA. The similar results were observed across disease states (stable vs. exacerbation) and degrees of hypercapnia. PetCO2-PA and PtcCO2 exhibited comparably diagnostic accuracy for hypercapnia (PaCO2 ≥ 45 or 50 mmHg), each achieving an area under the curve (AUC) greater than 0.94, with no statistically significant inter-method differences. The proportions of measurements exceeding the clinical acceptability thresholds of ± 4 mmHg and ± 7 mmHg did not differ significantly between techniques. PetCO2-PA demonstrated a small bias but a relatively wide LOA with PaCO2, non-inferior to PtcCO2, in patients with COPD. Owing to its cost-effectiveness, rapid operation, and portability, PetCO2-PA represented a practical alternative for screening and monitoring of hypercapnia in COPD patients. The trial was registered at ClinicalTrials.gov (identifier: NCT04051931).

Background:History of exacerbations is a predictor of future exacerbations in COPD but there are also predictors that are independent of exacerbation history. However, it is unclear whether their relative contribution is consistent across different degrees of airflow limitation. Methods:This analysis used data from COMPASS, a prospective study in COPD. Baseline demographics, clinical history, spirometry and patient-reported outcomes were collected. Multivariable models were created to predict moderate or severe exacerbations in the 18 months after baseline. Covariates included forced expiratory volume in 1 s (FEV1) % predicted, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade, modified Medical Research Council (mMRC) and COPD Assessment Test (CAT) scores, and exacerbation history. Goodness of fit was tested using C-statistics. Results:At baseline there were 1696 patients; 89.6% males, 46.9% current smokers, mean±sd age of 65.4±7.5 years, post-bronchodilator FEV1 66.6±20.1% predicted and 0.5±1.0 moderate/severe exacerbations in the prior year. Over 18 months, 17.8% of patients had ≥1 moderate/severe exacerbation. The best fit model identified six independent variables, C-statistic 0.739. Subgroup analysis into GOLD grades I, II and III+IV combined showed different predictor patterns. In grade I, history of moderate exacerbations was the strongest predictor, together with chronic bronchitis and gastro-oesophageal reflux. In grades III+IV, only history of severe exacerbations and mMRC score were significant. Grade II showed an intermediate picture in which severe exacerbations, chronic bronchitis and gastro-oesophageal reflux were all significant. Conclusions:There are multiple predictors of COPD exacerbations, which differ between GOLD grades. Future predictive models for exacerbation risk should take this into account.

Background:There is limited information available on patients with asthma in hospitals in China. We investigated their clinical and phenotypic characteristics and management. Methods:The China Asthma Data Registry Project (CHART) study is a multicentre, hospital-based, prospective, observational study in which patients were recruited from outpatient clinics. This analysis used baseline cross-sectional data from patients with asthma (≥12 years) enrolled at 58 tertiary hospitals in China between 25 March 2018 and 11 July 2019. Results:A total of 20 683 patients with asthma (56.2% female, 15.0% patients with active tobacco use) were enrolled. Overall, 22.8% had uncontrolled asthma, 39.5% had partially controlled asthma. Furthermore, 45.3% experienced ≥1 exacerbation annually, including 31.7% who required hospitalisation, with only 21.4% having previously used inhaled corticosteroids (ICSs) in the past year. Cough (80.0%) was the most common symptom, followed by wheezing (70.7%), with 14.6% having cough-predominant asthma and 11.4% having cough-variant asthma. Multivariate logistic regression revealed that cough severity independently predicted poor control, irrespective of airflow limitation or inflammatory status. The association was stronger in ICS users than in nonusers across all cough severity metrics: a visual analogue scale (VAS) score ≥40 (aOR 3.88-5.47 versus 2.49-2.94), a cough evaluation test (CET) score ≥12 (aOR 11.15-20.91 versus 3.97-5.55), and a Leicester Cough Questionnaire (LCQ) score <15 (aOR 6.15-13.66 versus 2.45-3.18). Conclusions:We found significant suboptimal control, a high prevalence of cough-related phenotypes, frequent exacerbations and hospital admissions in patients with asthma attending hospitals. This underscores the need to prioritise the assessment and treatment of cough in asthma.

Background: Following the 2021 first International Consensus on Severe Lung Cancer, global attention to patients with PS 2-4 has grown significantly. Recent advances in novel therapies, interventional techniques, and supportive care, along with emerging real world data, have expanded treatment opportunities for this population. To incorporate these advances, we have updated the consensus. Methods: A multidisciplinary panel comprising experts from oncology, radiation oncology, thoracic surgery, radiology, interventional medicine, respiratory medicine, critical care medicine, and nursing. After being presented with a comprehensive review of the current evidence pertaining to severe lung cancer and thorough discussions, the panel reached a consensus on 11 recommendations, each with over 70% expert agreement. Results: The 11 consensus points focused on definition and causes (n=2), assessment and general strategies (n=4), and specific treatment modalities (n=5) were updated or newly developed. This updated consensus emphasizes dynamic and precise detection, robust life support, flexible application of novel therapies, and MDT guided treatment adjustment based on PS dynamics. Early rehabilitation and comprehensive supportive care are integral to disease management. Conclusions: This consensus updates the definition, diagnostic evaluation, and treatment strategies, providing a practical framework for clinicians based on current evidence and multidisciplinary expert consensus. Prospective trials focusing specifically on patients with severe lung cancer are urgently needed.

BACKGROUND:Bronchiectasis and diabetes commonly coexist and are associated with immune dysfunction and increased susceptibility to infection. Although diabetes is associated with worse prognosis in cystic fibrosis-related bronchiectasis, data are scarce for its impact on non-cystic fibrosis bronchiectasis. This study aimed to characterise the impact of diabetes on clinical outcomes and microbial and inflammatory profiles in patients with bronchiectasis. METHODS:This analysis comprised data from the European Bronchiectasis Registry (EMBARC), Respiratory Research Network of India (EMBARC-India), Chinese Bronchiectasis Registry (BE-China), and Australian Bronchiectasis Registry (ABR); 30 263 patients with CT-confirmed bronchiectasis in 33 countries were included in the analysis: 16 963 from EMBARC (Jan 12, 2015, to April 12, 2022), 2361 from EMBARC-India plus additional Asian countries (June 1, 2015, to Sept 1, 2017), 10 324 from BE-China (Jan 10, 2020, to March 31, 2024), and 615 from the ABR (March 7, 2016, to Sept 11, 2018). Clinical data were compared between patients with and without diabetes. Long-term outcome data were available in EMBARC and EMBARC-India. Microbiome and inflammatory profiles were characterised in a sub-cohort of EMBARC patients by sputum 16S rRNA sequencing (n=433) and serum Olink (n=479). FINDINGS:2487 (8·2%) of 30 263 patients with bronchiectasis had diabetes. Patients with diabetes had a higher prevalence of comorbidities than those without diabetes, including cardiovascular disorders (53·5% vs 21·8%, p<0·0001), asthma (27·5% vs 21·0%, p<0·0001), and chronic obstructive pulmonary disease (34·3% vs 19·0%, p<0·0001). Patients with diabetes had more severe disease than those without diabetes, with higher Bronchiectasis Severity Index scores (8 [IQR 5-12] vs 7 [4-10], p<0·0001) and UK Medical Research Council (MRC) dyspnoea scores (p<0·0001) and more hospital admissions in the previous year (p<0·0001). After adjustment for confounders, outcomes were significantly worse in patients with diabetes than in those without diabetes, including more frequent exacerbations (incidence rate ratio [IRR] 1·18 [95% CI 1·09-1·28], p<0·0001), hospital admissions (IRR 1·57 [1·40-1·76], p<0·0001), and higher 5-year mortality (hazard ratio 1·80 [1·53-2·12], p<0·0001). The sputum microbiome was significantly altered in patients with diabetes compared to those without diabetes, with increased isolation of Enterobacteriaceae (p<0·0001), Moraxella catarrhalis (p=0·0035), and Haemophilus influenzae (p=0·046). In serum, Gal-4 and GDF-15, established biomarkers of disease severity and cardiovascular risk in diabetes, were significantly increased in patients with diabetes (Gal-4, p<0·0001; GDF-15, p=0·0019). INTERPRETATION:Patients with diabetes and bronchiectasis are a high-risk population with more severe disease, worse outcomes, increased comorbidities, and increased risk of infections compared with patients without diabetes. These findings support inclusion of diabetes as a risk factor in individualised risk assessments for bronchiectasis. FUNDING:European Respiratory Society, Armata, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Grifols, Insmed, Janssen, Lifearc, Roche, Verona Pharma, Zambon, National Natural Science Foundation of China, Innovation Program of the Shanghai Municipal Education Commission, Program of the Shanghai Municipal Science and Technology Commission, Program of the Shanghai Shenkang Development Center, EU/European Federation of Pharmaceutical Industries and Associations, Innovative Medicines Initiative, and Inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium.

Background:Airway clearance techniques (ACTs) are guideline-recommended in bronchiectasis, while contemporary patterns and determinants of ACTs adoption remain unclear in China. Methods:A multicentre cross-sectional study was conducted using data from the BE-China cohort between 10 Jan 2020 and 31 Mar 2024. Clinical characteristics and prespecified ACT modalities were collected across 92 hospitals. Multivariable logistic regression identified important associations of ACTs utilization. Findings:Among 9647 patients, 12.2% (1177) used regular ACTs at baseline, and regional heterogeneity in ACTs utilization was observed. Moreover, ACTs users exhibited prolonged disease duration, a higher proportion of severe disease, greater comorbidity, heavier cough and sputum burden, and more frequent pharmacological and ventilatory interventions. Variables associated with increased ACTs utilization included comorbid burden (OR 1.47, 1.28-1.70; p < 0.0001), daily sputum (OR 1.68, 1.33-2.10; p < 0.0001), expectorants usage (OR 3.19, 2.74-3.71; p < 0.0001), inhaled antibiotics (OR 2.04, 1.35-3.07; p = 0.00065), macrolide therapy (OR 2.31, 1.78-2.99; p < 0.0001), other long-term oral antibiotics (OR 1.37, 1.13-1.66; p = 0.0013), noninvasive ventilation requirement (OR 4.11, 3.14-5.39; p < 0.0001), and disease duration (per SD increase, OR 1.08, 1.01-1.15; p = 0.027). Both BE-China and the similar European Bronchiectasis Registry (EMBARC) cohorts showed distinct etiological and comorbidity profiles, yet consistently revealed a higher medication burden among ACTs users. Interpretation:In China, ACTs utilization is primarily concentrated among patients with bronchiectasis who have a heavier symptom burden and greater treatment intensity. Clinicians may leverage the identified associations to optimize adherence and guide phenotype-targeted ACTs implementation strategies, and these findings may serve as a reference for future research. Funding:Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Innovation Program of Shanghai Municipal Education Commission, Program of Shanghai Municipal Science and Technology Commission, Major Project of Guangzhou National Laboratory.