Wiley: Respirology: Table of Contents

An Age‐Friendly Approach to Caring for Chronic Lung Disease in the Ambulatory Setting

Angela O. Suen, Lauren R. Pollack, C. Adrian Austin, Leah J. Witt — Wed, 10 Jun 2026 20:20:44 -0700

ABSTRACT

Many common chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), have much greater prevalence among older adults and as a result, pose a substantial burden of morbidity, disability, and mortality. The care of older adults with chronic lung disease necessitates an age-friendly approach due to marked differences in physiology, clinical presentation, disease trajectories, and healthcare priorities as compared to younger adults. Pulmonary care models have historically prioritised disease-focused approaches over person-centered care. Disease-focused care fails to adequately address geriatric syndromes that complicate the management of chronic disease, such as multicomplexity, functional impairment, cognitive dysfunction, and psychosocial complexity. In this narrative review, we propose a deliberate, geriatrics-informed approach to ambulatory pulmonary care using the Age-Friendly 5Ms framework—What Matters, Medications, Mentation, Mobility, and Multicomplexity. This framework is an easy-to-use reference for chronic disease management and offers a practical roadmap to support clinical decision-making, inform health system improvement, and guide future research focused on outcomes that matter most to older adults living with chronic lung disease. We review how the 5 M framework helps to align care with patients' goals and values, minimize medication-related harms, address cognitive, psychological, and caregiving needs, preserve mobility and functional independence, and manage the intersecting medical and social challenges common in later life.

Supplemental Oxygen Therapy in Advanced Lung Disease—New Evidence Raises New Questions

Kristopher P. Clark, Anne E. Holland — Wed, 10 Jun 2026 01:30:46 -0700

Respirology, EarlyView.

Professional Development for the Clinician‐Educator in Respiratory and Sleep Medicine

Mark Lavercombe — Wed, 10 Jun 2026 01:21:13 -0700

Respirology, EarlyView.

Walking With Huffing: A Practical New Option for Airway Clearance During Bronchiectasis Exacerbations?

Xiu‐min Wu, Yong‐hua Gao — Thu, 04 Jun 2026 07:10:48 -0700

Respirology, EarlyView.

Baseline Neutrophil‐To‐Lymphocyte Ratio as a Risk Stratification Marker for Severe Checkpoint Inhibitor Pneumonitis in Patients With Non‐Small Cell Lung Cancer: A Two‐Cohort Study With Retrospective Discovery and Prospective Validation

Thu, 04 Jun 2026 05:44:56 -0700

The association between baseline neutrophil-to-lymphocyte ratio (NLR) and severe checkpoint inhibitor pneumonitis (CIP) was analyzed in discovery retrospective and validation prospective cohorts. Higher baseline NLR (≥ 4.75) was associated with increased severe CIP incidence in both cohorts. Baseline NLR is a promising risk stratification marker for severe CIP.

ABSTRACT

Background and Objective

Severe checkpoint inhibitor pneumonitis (CIP), particularly when it develops within 6–12 weeks, is a potentially fatal adverse event in patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Although neutrophil-to-lymphocyte ratio (NLR) has been reported to predict immune-related adverse events, its role in severe CIP remains unclear.

Methods

The discovery cohort retrospectively enrolled 102 patients with NSCLC treated with ICI monotherapy at Hiroshima University Hospital. The validation cohort prospectively enrolled 191 NSCLC patients receiving first-line treatment, including ICI, at 15 institutions. Severe CIP was defined as grade 3–5 pneumonitis occurring within 3 months of treatment initiation. The cut-off level of the baseline NLR was identified by receiver operating characteristic curve analysis in the discovery cohort, and the predictive accuracy was analyzed and confirmed in both cohorts.

Results

Severe CIP was observed in seven (6.9%) and 11 (5.8%) patients in the discovery and validation cohorts, respectively. In the discovery cohort, the baseline NLR was higher in patients with severe CIP than in those without (17.29 [4.76–20.73] vs. 3.70 [2.64–6.68], p = 0.006), and the cut-off level of the baseline NLR was set at 4.75 (AUC 0.81; sensitivity 85.7%, specificity 64.2%). The incidence of severe CIP was significantly higher in patients with higher baseline NLR levels (≥ 4.75) than in those without, in both cohorts (discovery: 15.0% vs. 1.6%, p = 0.009; validation: 10.3% vs. 3.3%, p = 0.046).

Conclusion

Baseline NLR is a promising risk stratification marker for severe CIP.

Recommendations From the Medical Education Editor

Mark Lavercombe — Thu, 04 Jun 2026 05:32:14 -0700

Respirology, EarlyView.

From Residency to Tissue Inflammatory Memory: HLF as a Transcriptional Gatekeeper of CD4 + Tissue‐Resident Memory T Cells

Masahiro Nemoto, Masahiro Kiuchi, Kiyoshi Hirahara — Tue, 02 Jun 2026 02:36:08 -0700

Respirology, Volume 31, Issue 6, Page 555-557, June 2026.

Thoracic Ultrasound as a Useful Adjunct to Examination of the Respiratory System

Fifian Ka‐yan Chiang, Macy Mei‐sze Lui — Tue, 02 Jun 2026 02:36:08 -0700

Respirology, Volume 31, Issue 6, Page 558-560, June 2026.

Breathing New Life Into Lung Cancer Detection: The Emerging Role of Breathomics

Chui Lyn Leong, Tracy Leong — Tue, 02 Jun 2026 02:36:08 -0700

Respirology, Volume 31, Issue 6, Page 552-554, June 2026.

Overcoming Missed Opportunities and Diagnostic Delay in Interstitial Lung Disease

Gin Tsen Chai — Tue, 02 Jun 2026 02:36:08 -0700

Respirology, Volume 31, Issue 6, Page 550-551, June 2026.

Issue Information

Tue, 02 Jun 2026 02:36:08 -0700

Respirology, Volume 31, Issue 6, Page 545-549, June 2026.

Novel Therapeutics for Chronic Obstructive Pulmonary Disease: From Empirical Bronchodilation to Precision Medicine

Naoya Fujino, Hisatoshi Sugiura — Tue, 02 Jun 2026 02:36:08 -0700

ABSTRACT

Chronic obstructive pulmonary disease (COPD) remains the third leading cause of death worldwide, and conventional bronchodilator-based therapies have limited efficacy in preventing exacerbations and disease progression. The 2024–2026 period represents a historic inflection point: three mechanistically distinct agents received Food and Drug Administration approval, marking the first substantive pharmacological innovation in over two decades and catalyzing a fundamental paradigm shift from empirical symptom management towards biomarker-driven, pathobiology-aligned precision medicine. In this comprehensive review, we synthesized emerging evidence on novel COPD therapeutics, encompassing dual phosphodiesterase-3/4 inhibitors, biologics targeting type 2 inflammatory pathways (interleukin [IL]-4/IL-13 and IL-5 axes), upstream alarmin antagonists (IL-33 and thymic stromal lymphopoietin), and emerging technologies including gene editing and senolytic therapy. We evaluated randomized controlled trials reporting reductions in exacerbations with biologic therapy in eosinophil-enriched populations. Central to this transformation is the “treatable traits” framework, in which COPD management shifts from categorical diagnosis towards identification and targeting of specific, modifiable pathobiological characteristics. We provide respiratory physicians with evidence-based guidance for treatment selection by leveraging validated biomarkers, discussing pharmacoeconomic considerations and implementation barriers in resource-limited settings, and identifying critical knowledge gaps requiring resolution. The convergence of biologics, small molecules, and emerging technologies positions COPD therapeutics at the threshold of disease modification.

Letter from the Singapore Thoracic Society: Vapours, Vapes, and Vaccines—Advancing Population Lung Health in Singapore

Jeffrey Shuen Kai Ng, Shera Tan, Sean Chee Hong Loh — Tue, 02 Jun 2026 02:36:08 -0700

Respirology, Volume 31, Issue 6, Page 651-653, June 2026.

Predicting Postoperative Complications in Patients With Lung Cancer and Idiopathic Pulmonary Fibrosis

Tue, 02 Jun 2026 02:36:08 -0700

This study introduces a novel scoring system to predict postoperative pulmonary complications in idiopathic pulmonary fibrosis patients undergoing lung cancer surgery. Validated across cohorts, it aids in risk assessment, offering a tool for safer and tailored management strategies.

ABSTRACT

Background and Objective

Postoperative pulmonary complications are common and can be fatal in patients with IPF undergoing lung cancer surgery. This study aims to develop a novel scoring system for predicting postoperative pulmonary complications (PPCs) in patients with idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC) undergoing surgical resection and help establish optimal treatment strategies.

Methods

We analysed data from 225 patients consisting of two cohorts who were diagnosed with IPF and who underwent curative resection for NSCLC. A scoring system was developed to predict postoperative pulmonary complications based on regression coefficients derived from a multivariable logistic regression model that included the following predictors: age, sex, diabetes, American Society of Anesthesiologists, diffusing capacity, and extent of surgery. Validation of the score was assessed through discrimination and calibration using a separate cohort of 51 patients.

Results

Among the 276 patients analysed, 95 (34%) experienced postoperative pulmonary complications. The final model identified six predictors (with corresponding scores), resulting in a total score of 0–10 points: age ≥ 65 years (1 point), male (1 point), American Society of Anesthesiologists class ≥ 3 (1 point), diabetes (2 point), diffusing capacity ≤ 65% (2 point), and extent of surgery (3 points). The area under the curve for the scoring system was 0.75 (95% CI, 0.69–0.82) in the derivation cohort and 0.73 (95% CI, 0.57–0.88) in the validation cohort.

Conclusions

This novel scoring system consisting of six easily accessible clinical variables may help predict postoperative pulmonary complications and guide treatment decisions.

Sympatho‐Excitation in Pulmonary Hypertension: The Potential Role of Pulmonary Arterial Baroreceptors: An Acute Physiologic Intervention Study

Tue, 02 Jun 2026 02:36:08 -0700

Pulmonary arterial baroreceptors reflexively stimulate sympathetic nerve activity (SNA) in response to elevated pulmonary artery pressure and distension. In pulmonary hypertension patients, changes in muscle SNA were proportional to changes in pulmonary haemodynamics following nebulised iloprost. Pulmonary arterial baroreceptor activation may contribute to deleterious sympatho-excitation in some patients with pulmonary hypertension.

ABSTRACT

Background and Objective

Sympathetic nerve activity is heightened in pulmonary arterial hypertension (PAH), promotes deleterious pulmonary vascular and right ventricular remodelling, and is associated with worsened exercise capacity and mortality. Pulmonary arterial baroreceptors, activated by increased pulmonary arterial pressure and distension, could drive muscle sympathetic nerve activity (MSNA) in pulmonary hypertension (PH). We hypothesised that pulmonary arterial baroreceptor unloading using nebulised iloprost as a pulmonary arterial vasodilator would lower MSNA in clinically stable treated PAH and chronic thromboembolic PH (CTEPH) patients.

Methods

In eleven PH patients (9 PAH, 2 CTEPH; 6 female; age 54 ± 14 years) common peroneal nerve microneurography was performed to record MSNA (n = 9) at baseline (10 min) and immediately following iloprost nebulisation (10 min). Concurrent measures of cardiorespiratory physiology and pulmonary haemodynamics (transthoracic echocardiography) were obtained.

Results

Iloprost reduced systolic pulmonary artery pressure (50 ± 19 mmHg baseline vs. 44 ± 15 mmHg iloprost; p = 0.040), and increased right ventricular outflow tract acceleration time (RVOT AT; 99 ± 15 ms baseline vs. 117 ± 16 ms iloprost; p < 0.001). Although no overall change was seen in MSNA (p > 0.05), the magnitude of change in MSNA burst size was inversely associated with the increase in RVOT AT (R² = 0.667, p = 0.0133).

Conclusion

These findings provide evidence suggestive of possible pulmonary arterial baroreceptor influence of MSNA burst amplitude in some PH patients. Pulmonary arterial baroreceptor activation may be a contributory mechanism to adverse sympatho-excitation in PH.

Clinical Trial Registration: ACTRN12622000494730

Lower CLAD and Good Survival in Lung Transplant Recipients With Pneumoconiosis: A Spanish National Multicentre Case–Control Study

Tue, 02 Jun 2026 02:36:08 -0700

This multicentre retrospective study evaluates lung transplantation outcomes in patients with pneumoconiosis, almost all with silicosis, comparing postoperative complications, long-term survival, and chronic lung allograft dysfunction (CLAD). Results show that despite higher surgical complexity, patients with pneumoconiosis experience similar postoperative outcomes and survival to other chronic lung disease patients, with a lower incidence of CLAD.

ABSTRACT

Background and Objective

Pneumoconiosis are irreversible fibrosing pulmonary diseases resulting from the inhalation of inorganic dusts. Lung transplantation (LT) is an option in advanced stages, but evidence on outcomes—especially early postoperative outcomes—remains limited. This national multicentre study evaluates LT outcomes in pneumoconiosis patients, almost all with silicosis.

Methods

A retrospective case–control study was conducted in 7 LT centres in Spain (2010–2023). A total of 81 LT cases due to pneumoconiosis (78 silicosis and 3 coal workers' pneumoconiosis) and 152 controls matched for age, sex, LT type, and LT date were included. Demographic, perioperative, and long-term follow-up variables were recorded. Postoperative complications, survival, and Chronic Lung Allograft Dysfunction (CLAD) were compared between groups.

Results

Pneumoconiosis LT recipients (1.77% of LTs performed) had greater surgical complexity, but no differences in immediate postoperative complications, long-term survival, or reinterventions. However, they presented a lower incidence of CLAD (p = 0.007) and a higher proportion of restrictive allograft syndrome (RAS) (p = 0.015) compared to controls. Median survival was 9.1 years (95% CI 4.9–13.2) in the silicosis group and 7.9 years (95% CI 5.2–10.6) in controls (p = 0.839).

Conclusion

LT in well-selected pneumoconiosis patients, predominantly with silicosis, is a viable alternative with outcomes comparable to other chronic lung diseases. Despite surgical complexity, no differences were identified in postoperative outcomes or survival. The lower CLAD incidence opens new research avenues on underlying immunopathogenic mechanisms.

Longitudinal Subphenotyping of Acute Respiratory Distress Syndrome: Implications in Prognostic Prediction and Clinical Intervention

Tue, 02 Jun 2026 02:36:08 -0700

Our findings provided a dynamic perspective on ARDS heterogeneity, which could improve risk prediction and guide personalized treatment decisions.

ABSTRACT

Background and Objective

To identify the longitudinal subphenotypes (LSPs) in patients with acute respiratory distress syndrome (ARDS) and their transitions, and to evaluate their potential for prognostic prediction and guiding interventions.

Methods

This retrospective multicohort study derived its cohort from Zhongshan Hospital, Fudan University, China. Feature selection was performed using univariate analysis, recursive feature elimination, and correlation analysis, followed by longitudinal latent profile analysis. Cox regression model was used to compare differences in mortality and responses to interventions. A predictive model was developed through selection from nine candidate machine learning algorithms followed by grid search optimization and subsequently applied to an independent validation cohort.

Results

Nine hundred ninety seven patients were included in the derivation dataset. Utilizing the 20 most prognostically relevant variables, three distinct LSPs were identified. Based on Day 1, the LSPs accounted for 36.41%, 36.71%, and 26.88%, respectively. LSP 1 (HR 5.119; 95% CI: 3.657–7.165) and LSP 2 (HR 2.922; 95% CI: 2.063–4.139) were associated with higher mortality. Both high-dose corticosteroids and invasive mechanical ventilation failed to elicit a treatment response in LSP 2 and LSP 3. Conversely, prone positioning proved to be an effective intervention for LSP 2. An early shift from LSP 1 to LSP 2 was associated with increased mortality (HR 1.679; 95% CI: 1.051–2.683). Furthermore, the optimized random forest model demonstrated superior performance in differentiating the three LSPs and could identify consistent subphenotypes in validation cohort.

Conclusions

Our findings underscore the importance of incorporating temporal subphenotype evolution into prognostic stratification and personalized treatment.

Breathomics Analysis for Early Diagnosis of Lung Cancer Based on PTR‐TOF MS: A Large Sample Size Cross‐Sectional Study

Tue, 02 Jun 2026 02:36:08 -0700

This study demonstrates that breath analysis using PTR-TOF MS and machine learning accurately distinguishes early lung cancer from benign nodules in a large cohort, identifying key biomarkers like alpha-pinene and methyl methacrylate for non-invasive screening.

ABSTRACT

Introduction

Lung cancer remains a leading cause of cancer mortality globally, emphasising the critical need for non-invasive and cost-effective early screening methods. Breath analysis, detecting disease-specific volatile organic compounds (VOCs), presents a promising diagnostic avenue.

Methods

This cross-sectional study enrolled 4515 participants, including 4099 nonmalignant controls and 416 lung cancer patients. Exhaled breath samples were analysed using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF MS). Machine learning algorithms, particularly Light Gradient Boosting Machine (LGBM), were employed to construct classification models for distinguishing lung cancer from healthy controls and early-stage lung cancer from benign pulmonary nodules. Model interpretability was assessed using SHAP values.

Results

The LGBM model demonstrated superior performance, achieving 95% sensitivity, 98% specificity, and 98% accuracy for discriminating lung cancer from healthy controls. For the clinically challenging task of distinguishing early-stage lung cancer from benign nodules, LGBM achieved 97% sensitivity, 98% specificity, and 98% accuracy. SHAP analysis identified alpha-pinene (m/z 137) and methyl methacrylate (m/z 101) as the most significant VOCs.

Conclusion

This large-scale study validates PTR-TOF MS based breath analysis combined with machine learning as a robust, non-invasive tool for early lung cancer detection. The LGBM model, supported by SHAP interpretability, offers high diagnostic accuracy in large cohorts. Future work will expand to diverse histological subtypes and multicenter validation.

Trial Registration

ChiCTR2500101879

Characterising Patient Pathways Prior to the Diagnosis of Interstitial Lung Disease

Tue, 02 Jun 2026 02:36:08 -0700

ABSTRACT

Background and Objective

Interstitial lung diseases (ILDs) lead to breathlessness, cough, deteriorating quality of life and early death. Patients are typically diagnosed late in their disease course when existing lung damage cannot be reversed. Accordingly, early diagnosis is the best strategy for preserving lung function and extending lifespan. Our aim was to identify signs, symptoms and health patterns and determine when they arise in the years preceding ILD diagnosis.

Methods

We identified incident ILD cases from a large primary care electronic medical record database from the United Kingdom. Prevalence and timing of symptoms, signs and health patterns were compared to matched controls in the 10 years preceding diagnosis.

Results

ILD patients (N = 18,914) had symptoms of dyspnoea, cough, fatigue, weight loss and loss of appetite recorded more frequently compared to controls (N = 60,156). Most patients (73%) reported cough or dyspnoea at least once at a primary care visit, with 13%–17% recording symptoms on ≥ 5 separate occasions (dyspnoea: 13% cases, 5% controls; cough: 17% cases, 7% controls). ILD patients had a greater cumulative incidence of cough and dyspnoea even 10 years before diagnosis (OR: 1.73 [1.58, 1.89], p < 0.001), with the odds ratio increasing to 2.38 at 1 year before diagnosis. Most ILD patients were initially diagnosed with another respiratory condition (95%–97%) or heart failure (4%–9%).

Conclusion

Gradual onset of non-specific symptoms over 10 years, coupled with referrals to other specialities and misdiagnoses, delays ILD diagnosis. Improving awareness of ILD among primary care practitioners may shorten the time to diagnosis and expedite access to treatments.

Association of Endotypic Traits and Their Interaction With Severity of Obstructive Sleep Apnea

Tue, 02 Jun 2026 02:36:08 -0700

ABSTRACT

Background and Objective

Endotypic traits of obstructive sleep apnea (OSA) are being increasingly identified as potential treatment targets. Nevertheless, their clinical relevance remains debated, as they are not consistently associated with OSA severity. This study aimed to examine endotypic traits' associations and their interaction effects with OSA severity.

Methods

A total of 1167 adults with moderate-to-severe OSA were prospectively recruited from a sleep center and underwent in-laboratory full-night polysomnographic studies. Endotypic traits—collapsibility (V_passive, ventilation at eupenic drive), loop gain, arousal threshold, and compensation—were estimated using polysomnographic signals, and OSA severity was examined by apnea-hypopnea index (AHI) and hypoxic burden. The associations between individual endotypic traits and OSA severity were visualised using generalised additive models. The interaction between arousal threshold and compensation on OSA severity was examined.

Results

A more collapsible upper airway and higher loop gain were linearly associated with greater OSA severity. Arousal threshold was positively associated with hypoxic burden, whereas the relationship between arousal threshold and AHI followed an inverse U-shaped pattern. Among patients with a relatively low arousal threshold (< 173.5 %eupnea), favourable upper airway patency was observed, and AHI increased with rising arousal threshold. The combination of a high arousal threshold and high compensation was associated with elevated AHI during NREM sleep, where the high compensation resulted from a very low V_passive.

Conclusions

A higher arousal threshold predicted a more severe hypoxic burden but showed a nonlinear association with AHI. Arousal threshold and compensation should be considered together when evaluating OSA severity.

New Obstructive Sleep Apnoea Multi‐Night Diagnostic Devices. Is a Single Night of Measurement Now Considered Enough?

Thomas J. Altree, Robert J. Adams — Sun, 24 May 2026 19:19:37 -0700

Respirology, EarlyView.

Few‐Shot Lung Cancer Classification via Electronic Nose Using Large Language Models: A Multicentre Prospective Study

Thu, 21 May 2026 16:21:08 -0700

Few-shot adaptation of pretrained large language models for lung cancer classification using electronic nose breathprints. LLM achieved AUC 0.76–0.79 with only 6 samples per class, significantly outperforming CNN models in few-shot scenarios. LLM facilitates practical eNose-based lung cancer classification by reducing dependence on large training datasets.

ABSTRACT

Background and Objective

Electronic Nose (eNose) breathprints are promising non-invasive lung cancer diagnostic tools, but cross-site validation and adaptation remain barriers to clinical applications. It remains unknown whether a natural language processing-pretrained large language model (LLM) can enable few-shot, site-specific classification of lung cancer using eNose breathprints.

Methods

We collected eNose breathprints of lung cancer and non-lung cancer patients from two medical centres in Taiwan. A GPT-2–backbone LLM with parameter-efficient adaptation was compared with convolutional neural networks (CNN) trained from scratch or pretrained on CIFAR-100. Few-shot protocols (2–6 shots per class) and full-data training were evaluated.

Results

We collected 432 eNose breathprints from two sites (S1 and S2). With 6 labelled samples per class (6 shots), LLM achieved an area under the curve (AUC) of 0.79 (95% CI: 0.71–0.87), sensitivity of 0.74 (0.63–0.83), and specificity of 0.77 (0.67–0.87) on S1. On S2, it achieved an AUC of 0.76 (0.69–0.82), sensitivity of 0.77 (0.69–0.84), and specificity of 0.61 (0.51–0.70). LLM outperforms scratch CNN models (S1; AUC: 0.44, p = 0.0002) (S2; AUC: 0.63, p = 0.0198) and CNN pretrained on CIFAR-100 images (S1; AUC: 0.57, p = 0.0100) and (S2; AUC: 0.61, p = 0.0248). LLM or a CNN model trained on the source site fails to improve performance after transferring to the target site for fine-tuning; for the LLM, performance even deteriorates.

Conclusion

Our study demonstrates the potential of pretrained LLMs for few-shot lung cancer classification in a real-world mixed clinical cohort, reducing dependence on large training datasets.

Preliminary Development of a Patient‐Reported Outcome Measure for Inducible Laryngeal Obstruction: Findings From a Delphi Process

Siobhan Ludlow, Stephen Fowler, Jamie Kirkham, Lucie Byrne‐Davis — Tue, 19 May 2026 16:18:27 -0700

Currently there are few patient-reported outcome measures for inducible laryngeal obstruction which characterise the multidimensional impact of the disease. The Delphi survey identified which items were important to include from a patient and health care professional perspective. The ILO-PROM will be a valuable clinical and research outcome measure in the future.

ABSTRACT

Background and Objective

Inducible laryngeal obstruction (ILO) is a laryngeal disorder that intermittently affects breathing. A psychometrically robust patient-reported outcome measure for ILO is required. We have generated items from individual patient interviews and a scoping review. The objective of this study is to ascertain which items covering the physical, social, and psychological impact of ILO were relevant for measuring the impact of living with ILO to inform a new patient-reported outcome measure.

Methods

An international two-round online Delphi study was conducted amongst a group including patients with ILO and relevant health care professionals. Participants judged the relevance of 80 items about the impact of ILO on a 9-point scale. We defined consensus as a minimum of 70% of participants rating items as 7–9. Participants were asked to give a reason for their ratings.

Results

Forty-six participants registered for the Delphi survey, with 37/46 (80%) and 29/37 (78%) completing rounds one and two, respectively. Participants were patients living with ILO (63%), respiratory physicians (10%), speech and language therapists (16%), physiotherapists (5%), a psychologist (3%) and a nurse (3%). Consensus was reached after round two for 37/80 (46%) to include, 11/80 (14%) not important to include and 32/80 (40%) being important but not critical to include [therefore 43/80 (54%) excluded].

Conclusion

Stakeholders agreed on 37 items that should be included in a PROM for ILO. Further studies to establish the psychometrics of a PROM based on these items are required.

Active Cycle of Breathing Technique Versus Oscillating Positive Expiratory Pressure Therapy Versus Exercise With Huffing During an Exacerbation of Bronchiectasis: A Randomised, Controlled Trial

Tue, 19 May 2026 16:04:21 -0700

Walking with huffing and the active cycle of breathing technique produced similar improvements in sputum expectoration and quality-of-life during hospitalisation for individuals experiencing a bronchiectasis exacerbation, while oscillating positive-expiratory-pressure therapy produced minimal changes.

ABSTRACT

Background and Objective

The relative effectiveness of airway clearance techniques (ACTs) during an exacerbation of bronchiectasis is unknown. This study aimed to compare the effects of three ACTs on sputum expectoration, health-related quality-of-life (HRQOL), and exacerbation rates in adults hospitalised with an exacerbation of bronchiectasis.

Methods

A randomised controlled trial of active cycle of breathing technique (ACBT), oscillating positive expiratory pressure (OPEP) therapy and walking with huffing. Sputum wet weight was collected during ACT sessions, 1-h post-session and the following 23 h on day 2 and day of discharge. HRQOL was assessed using the Quality of Life-Bronchiectasis (QoL-B) questionnaire and Leicester Cough Questionnaire (LCQ) on day 2 and day of discharge. Time to first exacerbation was explored for 6 months following discharge.

Results

Fifty-five participants were recruited. ACBT was associated with smaller sputum wet weight 1-h post session on day of discharge compared to walking with huffing (mean difference −2.58 g); no other significant differences between groups in sputum weights were observed. ACBT and walking with huffing significantly improved selected measures of HRQOL (LCQ total score and multiple QOL-B domains) at hospital discharge while OPEP therapy produced minimal changes. ACBT (158 days, 95% CI 139–177) resulted in a longer time to first exacerbation than walking with huffing (118 days, 95% CI 83–154) and OPEP therapy (89 days, 95% CI 69–111) but this finding should be interpreted with caution due to loss to follow-up.

Conclusion

Walking with huffing and ACBT gave similar improvements in sputum expectoration and HRQOL during hospitalisation in adults with an exacerbation of bronchiectasis.

Trial Registration

The study was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12621000428864) on 16-04-2021

RAP/PAWP Following CTEPH Surgery: A Simple Ratio for Complex Risk

Saeed Torbati, Colm McCabe — Mon, 18 May 2026 20:15:28 -0700

Respirology, EarlyView.

High Respiratory Arousal Threshold as a Potential Pathophysiological Biomarker of Excessive Daytime Sleepiness in Obstructive Sleep Apnoea

Danny J. Eckert — Mon, 11 May 2026 18:14:37 -0700

Respirology, EarlyView.

Microbial Phenotyping in COPD Exacerbations: One Step Closer to Precision‐Based Management

Carlos Andrés Celis‐Preciado, Simon Couillard — Tue, 05 May 2026 22:00:37 -0700

Respirology, EarlyView.

Prenatal PM2.5 Exposure and Airway Mechanics in Taiwanese Schoolchildren: Identifying Critical Windows of Susceptibility

Fri, 24 Apr 2026 00:39:29 -0700

This study investigated the association between prenatal PM_2.5 exposure and airway mechanics in school-age children. Elevated PM_2.5 exposure during late pregnancy was associated with adverse changes in childhood airway mechanics, highlighting a critical window of susceptibility. The findings suggest that reducing prenatal PM_2.5 exposure may improve long-term respiratory health in children.

ABSTRACT

Background and Objective

Exposure to ambient particulate matter ≤2.5 μm (PM_2.5) is associated with lung function impairment, particularly in children. However, the impact of prenatal PM_2.5 exposure on childhood airway mechanics remains unclear. We aimed to assess associations between prenatal PM_2.5 exposure and airway mechanics in school-age children.

Methods

Data from 1324 singleton children (745 boys, 56.3%; mean age, 6.5 years) participating in a population-based cohort in Taiwan were analysed. Prenatal ambient PM_2.5 exposure near residence was estimated using hybrid kriging-land use regression models with an XGBoost algorithm. Airway mechanics were measured by impulse oscillometry.

Results

Each 10 μg/m³ increase in prenatal PM_2.5 exposure across the entire pregnancy was associated with higher total airway resistance (R₅: β, 0.67; 95% CI, 0.30–1.03), proximal airway resistance (R₂₀: β, 0.37; 95% CI, 0.12–0.62), peripheral airway resistance (R₅-R₂₀: β, 0.30; 95% CI, 0.05–0.55), and airway impedance (Z₅) (β, 0.58; 95% CI, 0.21–0.94). Distributed lag nonlinear models identified sensitive windows during late pregnancy: 30–34 gestational weeks for R₅, 30–34 gestational weeks for Z₅, and at 26–33 gestational weeks for AX, respectively. Stratified analyses indicated stronger associations in girls, children exposed to prenatal environmental tobacco smoke, and those not breastfed.

Conclusion

Higher prenatal PM_2.5 exposure, particularly during late pregnancy, may be associated with adverse changes in airway mechanics in school-age children, especially girls, children exposed to prenatal environmental tobacco smoke, and those not breastfed, highlighting the importance of minimizing PM_2.5 exposure during late pregnancy to protect long-term respiratory health.

Heated Tobacco Product Use and Lower Physical Activity Among Japanese Adults With and Without Respiratory Diseases: Findings From the JACSIS Study

Mitsuo Hashimoto, Hiroki Yoshida, Takahiro Tabuchi — Thu, 23 Apr 2026 23:09:58 -0700

This study examined the association between heated tobacco product (HTP) use and physical activity among Japanese adults, including those with respiratory diseases. HTP users showed markedly lower activity levels than never smokers. Smoking cessation, particularly in asthma, should be prioritized, alongside promoting physical activity among tobacco users.

ABSTRACT

Background and Objective

Physical inactivity contributes to adverse health outcomes and is particularly detrimental in respiratory diseases. Despite being promoted as safer cigarette alternatives, the behavioural effects of heated tobacco products (HTPs) on physical activity remain unclear. This study examined the association between HTP use and physical activity among Japanese adults, particularly those with respiratory diseases.

Methods

A cross-sectional study used data from the 2023 Japan COVID-19 and Society Internet Survey (JACSIS), including 28,353 participants aged ≥ 15 years. Tobacco use was classified as never, current, or former use of cigarettes and/or HTPs. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) and expressed in MET-min/week. Multivariable analyses applied analysis of covariance (ANCOVA) and logistic regression comparing low versus moderate/high physical activity, adjusting for demographic, behavioural, and health factors.

Results

Predicted means of physical activity from the ANCOVA model were 1100.9 for never smokers, 1006.8 for cigarette smokers, and 945.6 MET-min/week for HTP users. Current cigarette smokers (β = −94.1 [95% CI: −176.7 to −11.5], p = 0.026) and current HTP users (β = −155.3 [95% CI: −252.7 to −57.9], p = 0.002) exhibited significantly lower physical activity than never smokers. Sensitivity analyses using log-transformed IPAQ scores and logistic regression confirmed these findings. Subgroup analyses indicated reduced activity among HTP users with asthma, but no clear pattern for COPD.

Conclusion

Cigarette smoking and HTP use were associated with lower physical activity, independent of confounders. Smoking cessation, particularly in asthma, should be prioritized, alongside promoting physical activity among tobacco users.

Right Atrial Pressure/Pulmonary Artery Wedge Pressure Ratio Correlates With Early Outcomes After Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension

Thu, 23 Apr 2026 22:43:54 -0700

The association between the right atrial pressure/pulmonary artery wedge pressure (RAP/PAWP) ratio and early postoperative outcomes in CTEPH patients undergoing pulmonary endarterectomy. RAP/PAWP ≥ 1 was associated with higher early postoperative complications, including reperfusion edema and prolonged hospital stay. The RAP/PAWP ratio serves as a simple, clinically intuitive tool to identify patients at higher risk for early postoperative morbidity, facilitating preoperative counselling and ICU resource allocation.

ABSTRACT

Background and Objective

The expected right atrial pressure (RAP) to pulmonary arterial wedge pressure (PAWP) ratio is < 1. Inversion of this ratio (RAP ≥ PAWP) has been linked to poor outcomes in pulmonary arterial hypertension, but its relevance in chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. For patients undergoing pulmonary endarterectomy (PEA), this ratio may be associated with postoperative outcomes and guide postoperative management.

Methods

We retrospectively reviewed consecutive CTEPH patients who underwent PEA at the University of California San Diego from January 2021 to December 2023. RAP/PAWP ratios ≥ 1 and < 1 were compared for postoperative outcomes. Haemodynamic data were derived from preoperative right heart catheterization. Outcomes included reperfusion pulmonary edema (RPE), ventilator days, re-intubation, ICU and hospital length of stay (LOS), and 30-day mortality.

Results

A total of 462 CTEPH patients met study criteria. Of these, 128 (27.7%) were in the inverse group (RAP/PAWP ≥ 1) and 334 (72.3%) in the control group (RAP/PAWP < 1). The inverse group had worse baseline functional class, cardiac index, NT-proBNP, and more haemoptysis. Postoperatively, rates of RPE (14% vs. 6%, p = 0.005) and re-intubation (5% vs. 1%, p = 0.036) were higher in the inverse group. They also required more ventilator days (2 vs. 1, p < 0.001) and had longer ICU (4 vs. 3 days, p = 0.002) and hospital LOS (13 vs. 11 days, p < 0.001). Thirty-day mortality was numerically higher in the inverse group (3% vs. 1%), though not statistically significant (p = 0.080).

Conclusion

RAP/PAWP ratio > 1 prior to PEA surgery was associated with higher rates of early postoperative complications.

Upadacitinib Versus Tofacitinib in Anti‐MDA5‐Positive Dermatomyositis With Interstitial Lung Disease: A Multi‐Centre Cohort Study Emulating a Target Trial

Wed, 15 Apr 2026 06:04:34 -0700

Comparative effectiveness of upadacitinib versus tofacitinib in anti-MDA5-positive dermatomyositis with interstitial lung disease was tested. Upadacitinib was found to be non-inferior to TOFA in improving 6-month lung transplantation-free survival. Our findings support upadacitinib as an effective therapeutic option in this high mortality population.

ABSTRACT

Background and Objective

The treatment of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (MDA5⁺DM-ILD) remains a significant clinical challenge. To compare the effectiveness and safety of upadacitinib (UPA) versus tofacitinib (TOFA) upon 6-month lung transplantation-free survival in newly diagnosed MDA5⁺DM-ILD patients.

Methods

This multi-centre cohort study in China enrolled MDA5⁺DM-ILD patients treated from January 2020 to February 2025. Prevalent/incident new users and non-inferior design along with inverse probability treatment weighting (IPTW) were implemented to emulate randomized controlled trial.

Results

In the eligible cohort, a total of 106 patients were treated with UPA and 328 with TOFA. The crude 6-month lung transplantation-free survival rates were 71.7% (76/106) in the UPA group and 67.4% (221/328) in the TOFA group. In the IPTW-adjusted cohort, UPA showed a trend toward higher survival than TOFA (p = 0.067), with a weighted risk difference of 10.3% (95% confidence interval −0.4% to 20.2%) meeting the non-inferiority margin (non-inferiority p = 0.003). Sensitivity and subgroup analyses showed consistent results, with potentially greater benefit of UPA in incident JAK inhibitor users (as first-line treatment), monotherapy recipients (without combination with other immunosuppressants except steroid), and those with rapidly progressive ILD. Safety profiles were comparable between groups.

Conclusion

UPA was found to be non-inferior to TOFA in improving 6-month lung transplantation-free survival among patients with MDA5⁺DM-ILD, with comparable safety.

Predicting Failure at Initiation of High‐Flow Nasal Oxygen in Patients With COVID‐19: Literature Review, Development and Internal Validation of a Prediction Model

Tue, 14 Apr 2026 21:38:53 -0700

A prediction model was developed for high-flow nasal oxygen (HFNO) failure in acute hypoxemic patients with COVID-19 pneumonia using predictors available prior to HFNO initiation. This stable and good-performing model can assist in clinical decision-making at a critical point, aiding timely intervention for patients at risk of HFNO failure.

ABSTRACT

Background and Objective

High-Flow Nasal Oxygen (HFNO) can reduce the need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure (AHRF) from viral pneumonias, like COVID-19. Early prediction of HFNO failure is useful for timely decision-making at HFNO initiation. This study aimed to develop a prediction model for HFNO failure using predictors available just prior to HFNO initiation in patients with COVID-19 AHRF and compare its performance to existing models.

Methods

This multicenter, prospective observational cohort study included hospitalized patients from 10 centers in the Netherlands between December 2020 and July 2021. Adults who tested positive for SARS-CoV-2, had no treatment limitations, and initiated HFNO for hypoxemia were included. The primary outcome was HFNO failure, defined as the event of endotracheal intubation. Pre-defined candidate predictors were selected by multivariable logistic regression for prediction model development. Internal validation was conducted using bootstrapping.

Results

Out of 608 patients, 277 (46%) experienced HFNO failure. Independent predictors of HFNO failure included (odds ratio [95% CI]): age (1.02 [1.00–1.03]), urea (1.04 [1.00–1.08]), platelet count (0.94 [0.92–0.97]), respiratory rate (1.05 [1.02–1.08]), oxygen saturation (0.89 [0.84–0.94]), and FiO₂ (conventional oxygen 10–15 L/min vs. < 10 L/min: 3.00 [1.71–5.29], 15 L/min vs. < 10 L/min: 4.95 [3.19–7.70]) prior to HFNO initiation. The model C-statistic was 0.767; 95% CI [0.727–0.803], with excellent calibration (intercept: −0.005, slope: 1.001), and stable performance after internal validation.

Conclusions

This newly developed model, using variables available at HFNO initiation, effectively predicted HFNO failure in hospitalized hypoxemic patients due to COVID-19 pneumonia with good performance.

Registration Number Clinical Trial

Dutch Trial Registry: DTR, NL9067.

Ambient Air Pollution and Risk of ARDS and Mortality in Moderate to Severe COVID‐19

Tue, 14 Apr 2026 05:49:23 -0700

Short-term CO exposure increased ARDS incidence and 30-day mortality in moderate to severe COVID-19, while long-term NO₂ and PM₁₀ exposure elevated ARDS risk. Air pollutants, particularly CO, were consistent independent predictors of poor outcomes, highlighting the importance of incorporating air-quality factors into pandemic preparedness.

ABSTRACT

Background and Objective

Ambient air pollution is known to exacerbate respiratory illnesses. However, its impact on COVID-19 outcomes remains underexplored. We investigated the association between ambient air pollution and outcomes in patients with moderate to severe COVID-19.

Methods

We analysed 1867 hospitalized patients from a multicentre Korean cohort. Individual-level exposure to five air pollutants (SO₂, CO, NO₂, PM₁₀ and PM_2.5) was assessed over short-term (3-day) and long-term (3-year) periods. The risks of acute respiratory distress syndrome (ARDS) and 30-day mortality were evaluated using models adjusted for clinical and meteorological factors. Pollutant exposure was analysed both as quartiles and continuous variables to estimate effects per unit increase.

Results

Short-term CO exposure was associated with increased ARDS incidence (per 0.1 ppm increase OR 1.18) and 30-day mortality (HR 1.15). Long-term NO₂ exposure was associated with higher ARDS risk (per 1 ppb OR 1.11). Long-term PM₁₀ exposure was also associated with ARDS incidence (per 10 μg/m³ OR 2.24). For mortality, short-term NO₂ (per 1 ppb HR 1.02) and PM_2.5 (per 10 μg/m³ HR 1.14) exposure were additionally associated with increased risk. These associations were consistent in quartile-based analyses.

Conclusion

Both short- and long-term exposure to ambient air pollution were associated with worse COVID-19 outcomes, including ARDS and mortality. CO, often overlooked in pollution surveillance, showed the most consistent impact. These findings highlight the importance of air quality in pandemic preparedness and public health policy.

Determinants of Improved Dyspnea and Exercise Tolerance With Nasal High‐Flow O2 Therapy in Fibrotic Interstitial Lung Disease: A Pilot Physiological Study

Thu, 09 Apr 2026 00:00:00 -0700

We tested the respective effect of high-flow and supplemental O₂ from nasal high-flow O₂ therapy (NHFO₂) on dyspnea and exercise tolerance in fibrotic interstitial lung disease. Supplemental O₂ and NHFO₂ (but not high-flow) provided improvements in these outcomes at “iso-O₂ saturation” due to reduced ventilatory requirements. Physiological benefits derived from O₂ supplementation are thus likely primary drivers of dyspnea relief and improved exercise tolerance on NHFO₂ (vs air) in these patients.

ABSTRACT

Background and Objective

Severe hypoxemia, heightened dyspnea, and exercise limitation are hallmarks of fibrotic interstitial lung disease (f-ILD). Standard O₂ therapy (nasal prongs) fails, however, to correct hypoxemia with limited symptomatic benefits due to inspiratory flow-patient demand mismatch. Nasal high-flow O₂ therapy (NHFO₂) is a promising alternative, but the respective contribution of high-flow and supplemental O₂ to improved dyspnea and exercise tolerance remains unknown in f-ILD.

Methods

Sixteen patients performed, in a randomized order, endurance tests (70% peak power) under 4 conditions: air, supplemental O₂ (face mask, 9–12 L·min⁻¹), NHF_air [50–70 L·min⁻¹; inspired fraction of O₂ (FiO₂) = 0.21], NHFO₂ (50–70 L·min⁻¹; FiO₂ = 0.5). Endurance time and O₂ saturation (SpO₂), breathing pattern (respiratory plethysmography) and dyspnea (Borg CR-10) were compared across conditions.

Results

Supplemental O₂ (98 [2]%) and NHFO₂ (99 [3]%) increased isotime SpO₂ vs air (87 [17]%, p < 0.001). Exercise time improved on O₂ and NHFO₂ vs air and NHF_air (683[903], 690[1338], 346[247], 319[415]s, respectively, p < 0.001; O₂ vs NHFO₂, p = 0.117). Supplemental O₂ and NHFO₂ reduced isotime ventilation vs air (47 ± 22, 44 ± 20, 63 ± 29 L·min⁻¹, p < 0.001), driven by lower respiratory rates (36 ± 9, 37 ± 8, 44 ± 10 br·min⁻¹, p < 0.001). Supplemental O₂ and NHFO₂ reduced isotime dyspnea vs air (4[3.5], 3.5[2.5], 7 [3], p < 0.001) and NHFO₂ vs NHF_air (3.5[2.5] vs 6[1.5], p = 0.016). NHF_air lowered isotime ventilation (9.0 ± 6.2 L·min⁻¹, p = 0.012) but did not improve dyspnea and exercise time vs air.

Conclusion

Supplemental O₂ and NHFO₂ improved dyspnea and exercise time at “iso-O₂ saturation” in severely hypoxemic f-ILD. Physiological benefits from supplemental O₂ (including lower ventilation) are thus likely primary drivers of dyspnea relief and improved exercise tolerance on NHFO₂ vs air in f-ILD.

Clinical Trial Registration

NCT07129707 (registered at ClinicalTrials.gov).

Deep‐Learning Algorithm Diagnostic Support for Usual Interstitial Pneumonia Pattern Recognition in Fibrotic Interstitial Lung Disease

Wed, 01 Apr 2026 23:06:01 -0700

ABSTRACT

Background and Objective

High resolution computed tomography (HRCT) scan diagnostic classification for usual interstitial pneumonia (UIP) plays a critical role in therapeutic decision-making and clinical trial eligibility for interstitial lung disease (ILD) patients, but is subject to variability. A deep learning algorithm, the Systematic Objective Fibrotic Imaging Analysis Algorithm (SOFIA), has been validated to assist classification of HRCTs based on current guidelines. In this study, we evaluate the impact of SOFIA on inter-observer agreement for UIP classification and prognostic accuracy of clinicians' assessment of ILD HRCTs.

Methods

Radiologists and pulmonologists (reviewers) were invited to evaluate 203 HRCTs from a national fibrotic ILD registry, scoring each of four UIP categories (definite UIP, probable UIP, indeterminate, or alternative diagnosis). SOFIA outputs were then provided, and reviewers were able to reevaluate their scores. Changes in interobserver agreement for UIP classification and prognostic accuracy were calculated.

Results

Three hundred twelve reviewers (120 radiologists, 192 pulmonologists) from 49 countries evaluated 203 HRCT scans. Following SOFIA, inter-observer diagnostic agreement improved for definite UIP from moderate to good (ICC_pre = 0.54[0.50–0.60]; ICC_post = 0.70[0.66–0.74]), and for probable UIP from fair to moderate (ICC_pre = 0.30[0.27–0.35]; ICC_post = 0.53[0.49–0.58]). Following SOFIA, there was improved prognostic accuracy for reviewers' definite UIP, probable UIP, and indeterminate scores (significant change in c-index), and the proportion of reviewers whose probable UIP scores were significantly predictive of transplant-free survival increased by 42%.

Conclusion

Providing SOFIA algorithm output to clinicians reviewing HRCT scans improved diagnostic agreement and prognostic accuracy for fibrotic ILD. SOFIA may be a useful automated assistive tool to support improved diagnostic consistency.

Real‐World Evaluation of a Rapid Multiplex PCR Panel in Adults Hospitalized With COPD Exacerbations

Fri, 27 Mar 2026 00:00:00 -0700

The FilmArray Pneumonia plus Panel (FAPP) demonstrates superior microbial detection and diagnostic accuracy compared to standard-of-care tests in patients with COPD exacerbations. High-abundance bacterial detection is significantly associated with host immune response. Rapid multiplex PCR testing shows potential in guiding antibiotic use and phenotyping COPD exacerbations.

ABSTRACT

Background and Objective

The clinical utility of rapid multiplex PCR panels in patients with exacerbation of COPD (ECOPD) is undefined. We aimed to assess the clinical relevance of the BioFire FilmArray pneumonia plus panel (FAPP) testing in ECOPD in a real-world hospital setting.

Methods

A prospective observational study was conducted on 74 hospitalized ECOPD patients. Spontaneous sputum samples were analysed using FAPP alongside standard-of-care (SOC) tests. Microbial profiles were assessed, and patients were phenotyped based on FAPP findings.

Results

FAPP significantly increased the proportion of patients with identifiable pathogens from 36% by SOC tests to 78% (increase of 42%, p < 0.0001), primarily contributed by increased bacterial detection (increase of 47%, p < 0.0001), with a shorter turnaround time (median 6 h vs. 75 h, p < 0.0001). Staphylococcus aureus was the most prevalent bacteria, while Haemophilus influenzae predominated at high abundance (10⁶–≥ 10⁷ copies/ml). Respiratory viruses were detected in 27%, most frequently Influenza A. All in-panel cultured bacteria were concordantly detected by FAPP at high abundance. High-abundance bacterial detection was associated with significantly higher host immune response markers. The bacterial-predominant phenotype was associated with higher exacerbation severity, while the purely eosinophilic phenotype had a lower 180-day treatment failure rate compared to the unclassified phenotype.

Conclusion

FAPP significantly enhances microbial detection in patients with ECOPD. Appropriate utilization of FAPP might guide antibiotic decision-making and phenotyping in ECOPD. The potential of sputum multiplex PCR-based strategy to guide antibiotic decisions in ECOPD merits further research.

Differences in Endotypic Traits Between Obstructive Sleep Apnoea Patients With and Without Excessive Daytime Sleepiness

Lixia Wang, Xinjie Hui, Rong Huang, Yi Xiao — Wed, 18 Mar 2026 17:03:32 -0700

This study investigated the association between endotypic traits of obstructive sleep apnoea (OSA) and comorbid excessive daytime sleepiness (EDS). Multivariable logistic regression demonstrated that ArTH was independently associated with comorbid EDS. In linear regression model, OSA endotypic traits were associated with OSA severity in OSA with and without EDS.

ABSTRACT

Background and Objective

Obstructive sleep apnoea (OSA) is a heterogeneous disorder. Although excessive daytime sleepiness (EDS) is a hallmark symptom of OSA, many patients remain asymptomatic, and a subset continues to experience EDS despite optimal therapy. The endotypic traits underlying EDS in OSA remain poorly defined.

Methods

We conducted a cross-sectional study of 694 adults at a Beijing sleep center, including 542 participants with AHI ≥ 5 events/h. EDS was defined as an Epworth Sleepiness Scale score > 10. Four endotypic traits were derived from full-night polysomnography using the “Phenotyping Using Polysomnography” method. Associations with EDS were assessed by multivariable logistic regression, and relationships with OSA severity by generalized linear regression.

Results

Compared with OSA without EDS, OSA with EDS exhibited significantly higher loop gain (LG), arousal threshold (ArTH), and upper airway collapsibility, and lower upper airway muscle compensation (Vcomp) (all p < 0.05). Multivariable logistic regression identified ArTH as an independent correlate of comorbid EDS, with an odds ratio of 3.12 (95% CI: 1.24–8.02; p = 0.016) for the highest quartile of ArTH. In the fully adjusted linear regression model, collapsibility, LG, and ArTH were significant determinants of OSA severity in both subgroups, whereas Vcomp was predictive predominantly among patients with EDS.

Conclusions

This study suggests that elevated ArTH is an over-expressed trait in OSA patients with EDS, potentially amplifying the link between respiratory pathophysiology and daytime sleepiness. While LG and collapsibility remain key determinants of OSA severity, these findings highlight the value of ArTH-targeted strategies and endotype-informed stratification for personalized management.