BACKGROUND:Inequalities in chronic respiratory diseases persist, yet up-to-date evidence on outcomes remains limited. We described national mortality and exacerbation rates in people with asthma and chronic obstructive pulmonary disease (COPD) since the beginning of the COVID-19 pandemic and assessed variation by inequalities. METHODS:England primary care records from the General Practice Extraction Service data for Pandemic Planning and Research were linked to Hospital Episode Statistics and Office for National Statistics mortality data. Cohorts of primary care diagnosed asthma and COPD were defined prior to 1 November 2019. Monthly age-sex-standardised exacerbation rates (Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) and Internationl Classification of Diseases (ICD) 10 codes) and mortality rates (ICD-10 codes) were calculated from 1 November 2019 to 31 March 2025, stratified by sex, Index of Multiple Deprivation (IMD), ethnicity and region. RESULTS:The study included 7644 510 people with asthma and 1 211 975 with COPD. Mean monthly exacerbation rates were higher in females than males (33% and 30% higher for asthma and COPD, respectively), while mean monthly all-cause mortality rates were 13% and 15% higher in males than females. Mean monthly exacerbation and all-cause mortality rates were higher in IMD-1 compared with IMD-10 across all conditions (asthma: 123% and 100% higher, COPD: 68% and 41% higher, respectively). Mean monthly all-cause mortality and exacerbation rates were higher in the northeast than the southwest (asthma: 22% and 69% COPD: 15% and 42% higher, respectively). Outcome rates varied by ethnicity across conditions. CONCLUSIONS:Inequalities in chronic respiratory disease outcomes persist across England despite sustained policy focus on reducing health inequalities.
BACKGROUND:This study sought to describe the prevalence of lung hyperinflation in adults (≥18 years) with cystic fibrosis (awCF) and the effects of elexacaftor-tezacaftor-ivacaftor (ETI) on hyperinflation. METHODS:Consecutive awCF who initiated ETI at Cochin Hospital (Paris, France) and had performed body plethysmography within 12 months prior to ETI initiation were included. Abnormal lung volumes (including total lung capacity (TLC) and residual volume (RV)) were defined as > upper limit of normal (ULN) using the Global Lung Initiative reference values. Lung hyperinflation was defined as RV/TLC>ULN. Variables associated with hyperinflation prior to ETI initiation were identified using multivariate logistic regression analysis. Evolution of hyperinflation was examined by comparing data prior to and after 12 months on ETI. FINDINGS:Body plethysmography was available prior to ETI initiation in 297 awCF, of which 286 had also body plethysmography at 12 months after ETI initiation. Prior to ETI initiation, TLC, RV and RV/TLC ratio values greater than ULN were found in 14%, 69% and 76% of awCF, respectively. RV/TLC ratio inversely correlated with percent predicted forced expiratory volume in 1 s (ppFEV1; r=-0.86). Increasing age and the number of days on intravenous antibiotics in the previous year were independently associated with RV/TLC>ULN. RV/TLC decreased after 12 months of ETI (median (IQR) absolute decrease; -5.4 (-10.3 to -0.3) %, p<0.0001; n=286) but remained above ULN in 65% of awCF, including in some with normal ppFEV1. INTERPRETATION:Lung hyperinflation usually persists in awCF treated with ETI despite improvement in ppFEV1 and lung volumes.
Studying the associations between indoor mould contamination and blood inflammatory phenotypes may provide further insight into the mechanisms by which this environmental factor affects asthma.Among 1870 adults with current asthma from a population-based cohort, 29.6% reported visible mould in the dwelling. Paucigranulocytic (reference category), neutrophilic, eosinophilic and mixed phenotypes accounted for 58.8%, 3.8%, 34.5% and 2.9%, respectively. Visible mould was consistently associated with eosinophilic phenotype (OR 1.30 (95% CI 1.04 to 1.63)) whatever the analyses, with no heterogeneity by sex.Our findings suggest that mould contamination may contribute to type 2 inflammation, offering mechanistic insight into the effect of mould on asthma in adults.
Diarrhoea is the primary cause of nintedanib discontinuation in idiopathic pulmonary fibrosis. We investigated predictors in 100 prospective patients; 46% experienced diarrhoea, defined as common terminology criteria for adverse events V.5.0 grade ≥1. In a multivariable model (area under the curve 0.9056), lower standardised body surface area (adjusted OR 0.20, 95% CI 0.06 to 0.55, p=0.004) emerged as a significant independent predictor. A linear mixed model showed that dose adjustments managed symptoms without compromising 12-month forced vital capacity or diffusing capacity of the lungs for carbon monoxide trajectories (p>0.05). Small body size influences drug tolerability, suggesting that simple anthropometric measures can aid in baseline risk stratification to improve adherence.
Abstract Introduction Treatment initiation or intensification to prevent exacerbation of chronic obstructive pulmonary disease (COPD) is based on the identification of patients with high exacerbation risk. The commonly used high-risk category of at least 2 moderate or 1 severe exacerbation within the prior 12 months has limited supporting evidence. We aimed to test the discriminative accuracy and assess the clinical utility of various COPD exacerbation categories for predicting future exacerbations. Methods In the COPDGene and NOVELTY cohorts, for each 1-year and 2-year recall periods, we estimated 6 distinct categories of exacerbation frequencies: ≥1 moderate (M1), ≥2 moderate (M2), ≥1 severe (S1), ≥1 moderate and ≥1 severe (M1andS1), ≥1 moderate or ≥ 1 severe (M1orS1), and ≥2 moderate or ≥ 1 severe (M2orS1), each ascertained in 3 ways: within 1 year, in each of 2 consecutive years (suffix E), and over a rolling combined 2-year period (suffix R). We used the area under the receiver operating characteristic curve (AUC) and decision curve analysis to evaluate the discriminative accuracy and clinical utility of these 18 categories for predicting the occurrence of M2orS1 (current standard) in the subsequent year. Results In COPDGene (n = 3,035), for the prediction of future M2orS1, baseline M1orS1R had the highest AUC (0.69, 95%CI 0.67-0.71) vs. baseline M2orS1 (0.66, 95%CI 0.64-0.67; Δ = 0.03;p<0.001). In NOVELTY (n = 3,080), M1orS1R category had the highest AUC (0.87, 95%CI 0.85-0.88) vs. M2orS1 (0.75, 95%CI 0.72-0.77, Δ = 0.12;p<0.001). Decision curve analysis demonstrated that the two-year rolling patterns provided the highest clinical utility across a clinically relevant treatment threshold range of 5% to 30% (Figure). M1orS1R also had the highest AUC for predicting any exacerbation (M1orS1) in both COPDGene (AUC = 0.68, 95%CI 0.66-0.70) and in NOVELTY (AUC = 0.86, 95%CI 0.85-0.88). Conclusions At least 1 moderate or 1 severe exacerbation over the previous 2 years has the highest discrimination and confers the highest clinical utility for predicting high COPD exacerbation risk. Overall, the combination of higher performance of various exacerbation history patterns in terms of their statistical (AUC) and clinical utility (net benefit) indicates that using a two-year recall and a lower threshold for high-risk classification (any moderate/severe events) is superior to the current standard of care. This abstract is funded by: This work was supported by NHLBI R01 HL151421 (SPB and AN), U01 HL089897 and U01 HL089856, by NIH contract 75N92023D00011, and by a Team Grant from the Canadian Institutes of Health Research (PHT 178432). COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion. The NOVELTY study was funded by AstraZeneca.
BACKGROUND:Lung function measurement is central to assessing disease severity and monitoring progression in bronchiectasis. Although home spirometry is convenient for remote monitoring, there is limited evidence for its performance. AIMS:In an a priori defined substudy in the CLEAR trial (a multicentre, randomised, open-label study of hypertonic saline and carbocisteine versus usual care in bronchiectasis), we assessed the performance of home spirometry in adults with bronchiectasis using the PANACEA framework (seven domains: test Performance, disease mANAgement, Cost, patient Experience, clinician Experience, researcher Experience, and Access). METHODS:Participants performed supervised 'clinic' spirometry at five visits and unsupervised 'home' spirometry weekly and during exacerbations over 52 weeks. Analyses evaluated agreement, longitudinal variation, changes in lung function across exacerbations, measurement quality, adherence and patient experience. Agreement was evaluated using Bland-Altman analysis; other outcomes were summarised descriptively. RESULTS:257 participants had home spirometry data. Clinic and home spirometry demonstrated close agreement, with a mean forced expiratory volume in 1 s (FEV1) difference of 20 mL (95% CI -130 to 170). Variability decreased over time (coefficient of variation 12.25% to 8.81%). Among 462 exacerbations, 195 had spirometry data within 7 days of exacerbation start/end dates. A >100 mL decline in FEV1 occurred in 48% of exacerbations; 35% returned to within 100 mL of pre-exacerbation stable values by exacerbation end. Most spirometry sessions met American Thoracic Society/European Respiratory Society quality criteria, adherence declined over time while patient experience was generally positive. CONCLUSION:Home spirometry demonstrates good agreement with clinic spirometry, with variability between measurements decreasing over time. Home spirometry detected changes in lung function across exacerbations, although variability may limit interpretation at the individual patient level. With appropriate patient support to maintain adherence, home spirometry has potential as a tool for remote monitoring and decentralised clinical trials in bronchiectasis. TRIAL REGISTRATION NUMBER:ISRCTN89040295.
BACKGROUND:The human lung hosts a highly specialised immune microenvironment responsible for defence, repair and responses to pathogens and environmental insults. Animal models insufficiently recapitulate human-specific immune pathways, limiting translational insight into both acute and chronic respiratory diseases. Advances in organoids, organ-on-chip technologies and biofabrication have enabled increasingly realistic in vitro lung models; however, many systems still lack immune components and the complexity required to capture dynamic host-immune interactions. CONTENT:This review outlines the existing impact of immune-competent lung models on clinical drug development and disease mechanistic studies, as well as the future potential and the technical challenges with integrating immune cells into in vitro lung models that need to be overcome to maximise clinical relevance. We discuss major bottlenecks and corresponding potential solutions, including immune cell viability and phenotype maintenance, microenvironmental compatibility, recruitment dynamics and the reproducibility-complexity trade-off. We further explore how cutting-edge biofabrication approaches, including tunable extracellular matrices, bioprinting and engineered microvascular networks, enable physiologically relevant interactions between immune and resident lung cell populations. CONCLUSION:Collectively, these advances pave the way for improved immune-competent lung models to accelerate therapeutic discovery and enhance model translational relevance.
The minimum important difference (MID) for the incremental shuttle walk test (ISWT) in individuals with long covid was estimated using anchor-based and distribution-based methods. 397 participants (56 ± 13 years; 63.7% male) with long covid completed a 6-week rehabilitation programme and rated perceived change using the Global Rating of Change Scale (GRCS). Change in ISWT distance differed across GCRS categories (p<0.05); participants reporting slight improvement increased ISWT distance by 60.7±85.9 m. Receiver operating characteristic analysis identified an optimal cut-off of 35 m (area under the curve 0.70, 95% CI 0.61 to 0.79; p<0.05). Distribution-based methods yielded MID estimates of 40.1 m and 52.5 m, supporting an MID range of 35-60.7 m.
INTRODUCTION:A drug response assessment (DRA) is recommended before starting patients on hypertonic saline (HTS) due to the risk of bronchoconstriction. As part of the CLEAR trial (a randomised, open-label trial of HTS and/or carbocisteine versus usual care in bronchiectasis), we performed a post hoc analysis to explore the implementation and outcomes of DRAs. We aimed to remotely train/assess research coordinators in performing DRAs and determine patient safety/tolerability with HTS. METHODS:Research coordinators were remotely trained/deemed DRA competent. DRAs were conducted only in patients assigned HTS. Failure was classified as ≥15% forced expiratory volume in 1 s (FEV1) drop or 10%-15% drop with respiratory symptoms. RESULTS:54 research coordinators (20 sites) were remotely trained/deemed competent, and 52 conducted at least one DRA. 145 patients completed DRAs: 144 were correctly classified, one was misclassified as pass (found during quality checks). 12 were classified as fail in the first DRA: seven had ≥15% FEV1 drop, two had 10%-15% FEV1 drop with symptoms, one had severe coughing (clinical team did not recruit) and the reason was not documented for two. 11 repeated the DRA; nine passed and continued in the trial, two failed and were excluded. 142/145 were classified as pass and entered the trial. Of 142 patients who continued in the trial, 46 later withdrew from HTS. 17 withdrawals were related to issues with HTS tolerance despite passing the first DRA. DISCUSSION:DRA failure rate was low and did not identify medium-term/long-term tolerance to HTS, indicating that its utility as a screening tool for tolerability in this population is limited. TRIAL REGISTRATION NUMBER:ISRCTN89040295.
BACKGROUND:Pulmonary aspergillosis is a rare, high mortality lung infection caused by the Aspergillus sp. Chronic lung diseases and immunosuppression are known risk factors, but data on the impact of corticosteroids and their route of administration are limited. METHODS:To evaluate the association between corticosteroid use and pulmonary aspergillosis, we conducted a retrospective case-control study in all Danish citizens who redeemed at least one prescription for inhaled medicine between 1994 and 2025. We identified 1351 patients with aspergillosis other than allergic bronchopulmonary aspergillosis (ABPA) and matched them to controls (1:5) by age, sex and calendar year using risk set sampling. Conditional logistic regression was used to estimate adjusted incidence rate ratios (aIRRs) for chronic pulmonary aspergillosis (CPA) and invasive pulmonary aspergillosis (IPA) across dose categories and 90-day exposure windows. The use of risk-set sampling allowed for estimating IRRs. RESULTS:Inhaled corticosteroids were associated with non-ABPA aspergillosis in a dose-dependent manner (aIRR 1.7 (95% CI 1.3 to 2.2) for use ≤640 µg/day, aIRR 2.8 (2.2 to 3.6) for use >640 µg/day, compared with no use) but only associated with IPA for higher doses. Oral corticosteroids (OCS) were similarly associated with non-ABPA aspergillosis (aIRR 3.0 (95% CI 2.2 to 4.1) for OCS use ≤5.6 mg/day, aIRR 4.0 (2.9 to 5.4) for OCS use >5.6 mg/day, both compared with no use), affecting both CPA and IPA. The risk decreased with increasing time since exposure. CONCLUSION:Our results demonstrate a strong and seemingly dose-dependent association between both systemic and inhaled corticosteroid use and aspergillosis.
BACKGROUND:Obstructive sleep apnoea (OSA) is a prevalent sleep disorder strongly associated with metabolic syndrome. Visceral adiposity is the principal culprit of the metabolic syndrome leading to the development of OSA. The longitudinal relation between visceral adiposity and OSA remains unknown. METHODS:We included 311 subjects without OSA at baseline to examine the association between visceral adiposity and incident OSA and 559 subjects without visceral obesity at baseline to examine the association between OSA and incident visceral obesity in a general population sample. OSA was defined as an Apnoea-Hypopnoea Index (AHI) ≥5 events/hour or having been diagnosed or received treatment for OSA. Visceral obesity was defined as a lipid accumulation product (LAP) level higher than the 75th percentile of the overall sample. RESULTS:After a median follow-up duration of 9 years, higher LAP values at baseline predicted higher AHI at follow-up (β=0.19, p=0.001) and visceral obesity at baseline was associated with higher odds of incident OSA (OR 7.10, 95% CI 3.05 to 16.51) after adjusting for confounders. Furthermore, higher AHI values at baseline predicted higher LAP values at follow-up (β=0.09, p=0.002) and OSA at baseline was associated with incident visceral obesity (OR 2.87, 95% CI 1.28 to 6.43) after adjusting for confounders. This bidirectional association was only observed in adults younger than 55 years. CONCLUSIONS:The association between visceral adiposity and OSA is bidirectional and significant in young and middle-aged but not in older adults. Our findings suggest that visceral adiposity might be the target of preventative and therapeutic strategies for OSA.
