Thorax最新文献

{"title":"Early prediction of bronchopulmonary dysplasia by urinary metabolomics: a case-control study.","authors":"Luca Bonadies,Serena Calgaro,Matteo Stocchero,Paola Pirillo,Gabriele Poloniato,Lorenzo Zanetto,Laura Moschino,Giuseppe Giordano,Eugenio Baraldi","doi":"10.1136/thorax-2025-223090","DOIUrl":"https://doi.org/10.1136/thorax-2025-223090","url":null,"abstract":"OBJECTIVEBronchopulmonary dysplasia (BPD), the most frequent complication of extreme preterm birth, lacks not only of a comprehensive definition but also of effective treatments and predictive tools. Metabolomics is a valuable tool to unravel the underlying pathogenetic pathways of diseases and identify possible early markers. The objective of this study was to find metabolic signatures of subsequent BPD development, defined and stratified as per Jobe and Bancalari 2001 NHICD Consensus.METHODSIn this observational case-control study, we initially enrolled 161 very preterm unmatched infants, collected their urine samples during the first 24 hours of life and performed metabolomics evaluations on these samples. Patients were then followed until 36 weeks postmenstrual age. To reduce the influence of gestational age and other confounders on metabolome, we applied a nested case-control matching procedure that allowed the selection of 25 BPD cases and 25 non-BPD controls.RESULTSMultivariate and univariate data analysis led to the recognition of 17 metabolites related to BPD development in the first day of life, of which three were identified: L-Glutamic acid (p value=0.038), o-Hydroxyphenylacetic acid (p=0.039), L-Homoserine (p value=0.020). Some of these metabolites are known to play a role in the protection against oxidative stress and/or inflammatory response, two of the most known factors involved in BPD pathogenesis. In particular, L-Glutamic acid and its ionic form glutamate were increased in infants developing BPD suggesting a role as promising marker of the disease.CONCLUSIONSOur findings pave the way to better characterise early origin of BPD from a metabolic point of view towards a better biological framework of the disease and, eventually, its prediction and possible new treatments.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"29 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paternal prepubertal passive smoke exposure is related to impaired lung function trajectories from childhood to middle age in their offspring","authors":"Jiacheng Liu, Jennifer L Perret, Caroline J Lodge, Don Vicendese, Gayan Bowatte, Adrian J Lowe, Nur Sabrina Idrose, Peter Frith, Richard Wood-Baker, Gita D Mishra, John W Holloway, Cecilie Svanes, Michael J Abramson, Eugene Haydn Walters, Shyamali C Dharmage, Dinh S Bui","doi":"10.1136/thorax-2024-222482","DOIUrl":"https://doi.org/10.1136/thorax-2024-222482","url":null,"abstract":"Introduction Paternal prepubertal passive smoke exposure may increase the risk of childhood asthma. However, its association with impaired lung function trajectories at risk of chronic obstructive pulmonary disease in offspring was not investigated. We assessed the association between paternal prepubertal passive smoke exposure and lung function from childhood to middle age in their offspring. Methods Data were analysed from 890 father-offspring pairs from the Tasmanian Longitudinal Health Study. The offspring were probands in the original cohort who underwent spirometry at six time points from ages 7 to 53 years. Lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) trajectories were previously derived using group-based trajectory modelling. Fathers reported their own passive smoke exposure before age 15 years. Multinomial logistic regressions assessed associations between paternal prepubertal passive smoke exposure and lung function trajectories in offspring. Potential mediations and interactions were assessed for active paternal smoking, offspring passive smoke exposure and respiratory illnesses during childhood, and subsequent active smoking. Results Paternal prepubertal passive smoke exposure was associated with the below average FEV1 (adjusted multinomial OR (aMOR) 1.56; 95% CI 1.05 to 2.31) and early low-rapid decline FEV1/FVC trajectories (aMOR 2.30; 95% CI 1.07 to 4.94) in offspring. The association with the below average FEV1 trajectory was augmented for offspring exposed to childhood passive smoke (aMOR 2.36; 95% CI 1.34 to 4.13; p-interaction=0.053). Observed associations partly mediated through smoking and respiratory illnesses in fathers and offspring (each contributing <15%). Conclusions Paternal prepubertal passive smoke exposure was associated with impaired lung function trajectories in offspring, which highlights the adverse impact of smoking on multiple generations. Data are available on reasonable request. Individual participant data can be provided on request to anyone with a suitable proposal. The proposal will be reviewed by the steering committee of the Tasmanian Longitudinal Health Study (TAHS). Requests can be directed to SCD, the principal investigator of the TAHS and the corresponding author of this paper. Individual deidentified data for all TAHS participants may be provided.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"162 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of regional asthma guidelines on SABA prescribing patterns across England: an interrupted time series analysis","authors":"Dominic L Sykes, Michael D Clarkson, Anita Negbenebor, Helena Cummings, Shoaib Faruqi, Oscar Lau, Niranjanlal Ahilal, Michael G Crooks","doi":"10.1136/thorax-2025-223239","DOIUrl":"https://doi.org/10.1136/thorax-2025-223239","url":null,"abstract":"The 2024 British Thoracic Society/ National Institute for Health and Care Excellence/ Scottish Intercollegiate Guidelines Network asthma guidelines recommend anti-inflammatory reliever (AIR)-based management, providing opportunity to reduce short-acting beta agonist (SABA) over-use. Many English regions also publish local guidelines. Analysis of 34 regional guidelines enabled grouping into three categories: SABA-first, inhaled corticosteroid (ICS) plus SABA and AIR (as-needed AIR), based on recommended initial treatment. Interrupted time series analysis using publicly available data demonstrated that AIR guideline publication resulted in the greatest decline in SABA prescribing, expressed as the proportion of all ICS-containing and SABA inhaler prescriptions (AIR: −0.26% (SD 0.09%) per month; SABA-first: −0.1% (SD 0.03%) per month, p=0.001 vs AIR; and ICS plus SABA: −0.16% (SD 0.06%) per month, p=0.004, vs AIR). Therefore, regional guidelines do affect local prescribing practice and alignment with the latest national recommendations could improve asthma prescribing and resulting patient outcomes.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"28 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Journal club","authors":"Miguel Jiménez-Gómez","doi":"10.1136/thorax-2025-223776","DOIUrl":"https://doi.org/10.1136/thorax-2025-223776","url":null,"abstract":"Metastatic malignant pleural effusion (MMPE) is associated with highly variable survival, highlighting the need for accurate prognostic tools to guide clinical decision-making. The LENT score has traditionally been used to estimate median survival, whereas the PROMISE score was developed to predict 3 month mortality. A recent external validation of both models (ERJ Open Res 2025, DOI: 10.1183/23120541.01019–2024) in 773 patients revealed limitations. Although both scores demonstrated moderate discriminative ability for overall survival (Harrell’s C-statistics 0.72 for LENT, 0.73 for PROMISE), their median survival estimates lacked precision. Performance improved at fixed timepoints (3-, 6-, and 12 months mortality), with C-indices approaching 0.8. However, both scores underestimated survival in low-risk patients and lacked integration of tumor-specific features or oncogenic drivers such as EGFR mutations. Additionally, LENT includes mesothelioma and unconfirmed effusions, which may inflate survival estimates, while PROMISE requires biomarkers not always available in routine practice. To overcome these limitations, the GASENT model was recently developed prospectively in Galicia (Arch Bronconuemol 2025, DOI: 10.1016/j.arbres.2025.04.001) using a derivation cohort (n=475) and validated in an independent cohort (n=205). It incorporates six widely available variables: Age, Sex, ECOG-Performance Status, Neutrophil-to-Lymphocyte Ratio, and Tumour type. GASENT …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"24 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: British Thoracic Society Winter Meeting 2024","authors":"BMJ Publishing Group Ltd and British Thoracic Society","doi":"10.1136/thorax-2024-btsabstracts-corr1","DOIUrl":"https://doi.org/10.1136/thorax-2024-btsabstracts-corr1","url":null,"abstract":"Abstract withdrawn as it was not presented at the Meeting S34 - Reduced mucus plugging with tezepelumab is spatially associated with reduced air trapping in a broad population of patients with moderate to severe asthma S35 - Dupilumab Effect on Exacerbations and Lung Function Despite Withdrawal of Inhaled Corticosteroids/Long-acting Beta Agonists S101 - Impact of Early Transient Increase in Eosinophil Count on the Long-Term Efficacy of Dupilumab in Patients With Moderate-to-Severe Asthma: LIBERTY ASTHMA TRAVERSE S129 - How can gene editing of human pluripotent stem cells help understand the effect of genetics on respiratory diseases? …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"12 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in respiratory medicine: the need for integrated tuberculosis and respiratory care in low-resource settings","authors":"Jacqueline Wanjiku Kagima, Obianuju B Ozoh, Stellah Mpagama, Nora Engel, Maia Lesosky, Jason Madan, Jeremiah Chakaya, Jamilah Meghji","doi":"10.1136/thorax-2024-222170","DOIUrl":"https://doi.org/10.1136/thorax-2024-222170","url":null,"abstract":"Background Pulmonary tuberculosis (PTB) and chronic respiratory diseases (CRDs) are intricately linked. People with PTB and CRDs experience similar symptoms, including breathlessness, cough and chest pain. They may have similar risk factors for disease, including smoking and occupational exposures. PTB is also a direct cause of lung damage in the form of post-TB lung disease. However, despite the overlap in risk factors, symptoms and sequelae, public health and clinical care pathways for TB and CRDs remain almost entirely separate in many low- and middle-income countries (LMICs). Those with respiratory symptoms are directed to TB services as a first point of contact where they are known as ‘people with presumptive TB’, and pathways to respiratory diagnosis and care remain largely inadequate. Aim In this opinion piece we describe opportunities for the integration of tuberculosis (TB) and respiratory care, as a means of improving patient outcomes in LMICs. Strategies may include upstream public health interventions to address shared risk factors, the use of shared diagnostic pathways, the provision of decentralised access to both TB and CRD care, and coordinated information provision about the risk factors and symptoms of both conditions. Health-related benefits may include more timely diagnosis of CRDs, improved CRD treatment and care, and reduced inappropriate empirical TB treatment or retreatment. We highlight the need for pilot models of integrated care, with robust design and evaluation, and we note that an integrated approach may be particularly timely given the increasing scarcity of global health donor funding.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"8 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon gamma applied ex vivo restores function to neutrophils from critically ill patients","authors":"Cameron J Lake, Jonathan Scott, Marie-Hélène Ruchaud-Sparagano, John H Thompson, Fiona Dewar, Polina Yarova, Wendy Funston, Richard CH Davidson, Kathryn M Musgrave, Stephen E Wright, Ian Clement, Alistair I Roy, Wezi Sendama, Jason Powell, Daniel Brooks, Chung Mun Alice Lin, Kristen Davies, Thomas P Hellyer, Anthony J Rostron, A John Simpson","doi":"10.1136/thorax-2025-223280","DOIUrl":"https://doi.org/10.1136/thorax-2025-223280","url":null,"abstract":"Introduction Critically ill patients commonly develop acquired neutrophil dysfunction, which increases susceptibility to intensive care unit-acquired infection (ICU-AI). This study aimed to assess whether interferon gamma (IFN-γ) can restore function in dysfunctional neutrophils from critically ill patients and to uncover potential underlying mechanisms. Methods This was an observational cohort study. Neutrophils were isolated from whole blood donated by critically ill patients (n=31) in four separate teaching hospital intensive care units (ICUs). Neutrophils were subsequently treated with recombinant human IFN-γ or vehicle for 1 hour following either Fc gamma receptor (FcγR) blockade, selective inhibition of the gamma isoform of phosphoinositide 3-kinase (PI3K-γ) or vehicle control for 30 min. Neutrophil phagocytosis, bacterial killing, superoxide generation, phagocytic receptor expression and small Rho GTPase activity were assessed. Neutrophil dysfunction was defined as <50% of cells ingesting 2 or more zymosan particles in a phagocytosis assay. Results IFN-γ significantly improved phagocytosis (control 36.5%, IFN-γ 56.0%), bacterial killing (control 31.6%, IFN-γ 82.1%) and superoxide generation (2.8-fold increase relative to control) in dysfunctional neutrophils. IFN-γ also increased the activity of the small GTPases, Rac and Cdc42 (2.4-fold and 1.5-fold increase relative to control, respectively) in dysfunctional neutrophils. Selective inhibition of PI3K-γ prevented the IFN-γ-mediated improvement of phagocytosis (IFN-γ 62.5%, with inhibitor 27.9%), bacterial killing (IFN-γ 82.1%, with inhibitor 30.5%) and superoxide generation (IFN-γ 2.8-fold change relative to control, 0.7 with inhibitor). The IFN-γ-mediated improvement of bacterial killing in dysfunctional neutrophils was also prevented by FcγR blockade (IFN-γ 82.1%, FcγR inhibition 28.7%). Conclusions In critically ill patients with known acquired neutrophil dysfunction, ex vivo application of IFN-γ consistently improved a range of neutrophil effector functions. Data are available on reasonable request.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"7 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gabapentinoids and risk for asthma exacerbations: a nationwide retrospective cohort study","authors":"Yuya Kimura, Taisuke Jo, Norihiko Inoue, Maho Suzukawa, Hiroki Matsui, Yusuke Sasabuchi, Hideo Yasunaga","doi":"10.1136/thorax-2025-223240","DOIUrl":"https://doi.org/10.1136/thorax-2025-223240","url":null,"abstract":"Introduction Despite warnings from the US Food and Drug Administration about respiratory adverse events associated with gabapentinoids, direct evidence of their risk in patients with asthma is lacking. Methods Using a national administrative claims database, we prepared two active comparators—new user cohorts of patients with a history of neuropathic or chronic pain and asthma—initiating gabapentinoids and comparator drugs (tricyclic antidepressants (TCAs) or serotonin norepinephrine reuptake inhibitors (SNRIs)). Overlap propensity score weighting was used to control for potential confounders. The initial occurrence of asthma exacerbation requiring systemic corticosteroids (primary) or those requiring hospitalisation for asthma (secondary) was assessed using a weighted Cox proportional hazards model. Findings In the TCAs cohort (171 393 gabapentinoids users and 5916 TCAs users), gabapentinoids use was associated with a higher incidence of primary (59.4 vs 33.7 per 100 person-years; HR 1.46, 95% CI 1.34 to 1.60) and secondary outcomes (0.91 vs 0.42 per 100 person-years; 2.02, 1.11 to 3.68). In the SNRIs cohort (189 055 gabapentinoids users and 19 800 SNRIs users), using gabapentinoids was also associated with a higher incidence of primary outcome (63.5 vs 42.8 per 100 person-years; HR 1.24, 1.19 to 1.30). However, the difference in the secondary outcome did not reach statistical significance (0.93 vs 0.68 per 100 person-years; 1.24, 0.94 to 1.63). Interpretation Gabapentinoids were associated with an increased risk of asthma exacerbations compared with TCAs or SNRIs. Managing neuropathic or chronic pain in patients with asthma using gabapentinoids should be approached with caution. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"25 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence to the EAT-Lancet diet, plasma proteomics and the risk of chronic obstructive pulmonary disease","authors":"Xujia Lu, Yalong Pei, Yang Geng, Yulong Fan, Xinmei Lu, Lan Jiang, Yan Borné, Chaofu Ke","doi":"10.1136/thorax-2025-223046","DOIUrl":"https://doi.org/10.1136/thorax-2025-223046","url":null,"abstract":"Background and aims Adhering to the EAT-Lancet diet has been observed to be associated with lower risks of various morbidities. This study aimed to investigate the association of adhering to the EAT-Lancet diet with incident chronic obstructive pulmonary disease (COPD) and identify plasma proteins mediating such association. Methods This prospective study involved 202 340 participants free of COPD at baseline from the UK Biobank. Adherence to the EAT-Lancet diet was assessed by four different diet indices. Mediation effects of plasma proteins were investigated in a subcohort of 21 186 participants with information on plasma proteins measured by the OLINK Explore-3072 platform. Results Compared with individuals with the lowest adherence to the EAT-Lancet diet, those with higher adherence had a lower risk of developing COPD, and the HRs (95% CIs) for the highest adherence group versus the lowest were 0.607 (0.558 to 0.660) for the Willett EAT-Lancet index, 0.666 (0.593 to 0.748) for the Knuppel EAT-Lancet index, 0.586 (0.513 to 0.668) for the Stubbendorff EAT-Lancet index and 0.674 (0.620 to 0.732) for the Kesse-Guyot EAT-Lancet index. A total of 534, 149, 486 and 489 proteins showed significant mediation effects between the Willett, Knuppel, Stubbendorff or Kesse-Guyot EAT-Lancet index and incident COPD. The overall proteomic scores mediated 34.43% (95% CI: 22.86% to 53.45%), 24.15% (13.20% to 72.99%), 22.96% (14.53% to 41.13%) and 34.63% (21.26% to 60.38%) of the associations between the Willett, Knuppel, Stubbendorff or Kesse-Guyot EAT-Lancet index and incident COPD. Conclusion Higher adherence to the EAT-Lancet diet was associated with a lower risk of COPD, and a wide range of circulating plasma proteins mediated such association. Data may be obtained from a third party and are not publicly available. This study was conducted using the UK Biobank Resource under Application Number 60651. The data that support the findings of this study are available on application to the UK Biobank team at <http://www.ukbiobank.ac.uk/>.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"21 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum IgA isotypes are associated with percent emphysema, wall thickness and lung function decline","authors":"Tess Pottinger, Zhonghua Liu, Lili Liu, Kristina L Buschur, Jeffrey L Curtis, Ani Manichaikul, Stephen S Rich, Victor E Ortega, Eugene R Bleecker, Deborah A Meyers, Eric A Hoffman, Benjamin Smith, Jan Novak, Krzysztof Kiryluk, R Graham Barr","doi":"10.1136/thorax-2025-222990","DOIUrl":"https://doi.org/10.1136/thorax-2025-222990","url":null,"abstract":"Rationale Immunoglobulin A (IgA) deficiency, a rare, highly heritable trait, is associated with frequent pulmonary infections, emphysema, airway changes and low lung function; however, it is unclear if reduced IgA levels may affect lung structure and function. Methods Serum IgA, IgA1 and galactose-deficient IgA1 (Gd-IgA1) levels were measured in the population-based Multi-Ethnic Study on Atherosclerosis (MESA). The MESA Lung Study measured percent emphysema on cardiac CT and airway dimensions on chest CT, and performed spirometry. Regression models were evaluated after adjustment for demographic and CT factors. Mendelian randomisation (MR) analyses were conducted using genetic variants from the Trans-Omics for Precision Medicine (TOPMed) programme. A replication analysis was performed in the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). Measurements and main results Among 5497 participants, lower log-normalised serum IgA levels were associated with greater percent emphysema (β=−0.084; 95% CI −0.14 to –0.026; p=0.005), which was confirmed on MR (β=−0.79; 95% CI −1.4 to –0.18; p=0.011). Greater log-normalised serum Gd-IgA1 levels were associated with airway wall thickness (β=0.0079; 95% CI 0.0017 to 0.014; p=0.012; n=2580) and decline in the forced expiratory volume in one second (FEV1) (β=−0.012; 95% CI −0.021 to –0.0036; p=0.0055; n=2778) and FEV1/forced vital capacity (FVC) ratio (β=−0.0028; 95% CI −0.0048 to –0.00084; p=0.0054; n=2778). Conclusion Lower serum IgA levels were associated with greater percent emphysema. Additionally, higher Gd-IgA1 levels were associated with airway wall thickness and lung function decline. These findings support a protective role of IgA in emphysema pathogenesis and possible deleterious role of Gd-IgA1 in airway diseases. Data are available upon reasonable request. Data are available on reasonable request. The datasets supporting the conclusions of this article can be accessed by reasonable request to MESA Publication and Presentations (<https://www.mesa-nhlbi.org>) and SPIROMICS Publication and Presentation (<https://spiromics.org/spiromics>) in compliance with MESA, SPIROMICS and NHLBI/NIH data privacy and sharing standard practices and policy.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"190 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144898357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}