Pub Date : 2025-11-15DOI: 10.1136/thorax-2024-222908
Naesilla Naesilla, Jennifer K Quint, Verena Zuber
Background Chronic respiratory diseases (CRDs) and cardiovascular diseases (CVDs) are leading global health burdens. Despite being common, CRD and CVD comorbidity is often underestimated due to overlapping symptoms and risk factors. Consequently, their relationship remains unclear. Aims and objectives To determine the bidirectional genetic relationship between CRD and CVD and explore smoking and inflammation as potentially shared joint risk factors. Methods We conducted bidirectional Mendelian randomisation (MR) to explore CRD–CVD relationships. Summary statistics from genome-wide association studies were retrieved for chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease (CAD), myocardial infarction (MI), heart failure, atrial fibrillation (AF) and ischaemic stroke (IS). We performed additional analysis including univariable MR for smoking, multivariable MR adjusting for smoking and cis-MR to investigate the role of inflammatory markers. Results Our MR analysis found limited genetic evidence of relationships between CRD and CVD, and vice versa. However, a nominally significant genetic association was observed between asthma and an increased risk of AF (OR inverse-variance weighted (ORIVW) 1.036, 95% CI 1.003 to 1.070), remaining weakly significant after adjusting for smoking (ORIVW 1.040, 95% CI 1.008 to 1.074). Genetically predicted lifetime smoking strongly increased all CRD and CVD risk. Additionally, genetically proxied IL6R concentration associated with increased asthma risk and decreased CAD, MI, AF and IS risk, while IL1RN decreased COPD risk but increased CAD and MI risk. Conclusions While we found limited genetic evidence linking CRD and CVD, smoking and inflammatory markers commonly affect both. These findings highlight the complexity of CRD–CVD comorbidities, whose pathophysiology likely does not involve direct causation of each other. Data are available in a public, open access repository. Data may be obtained from a third party and are not publicly available. All data used in this study, except for two summary statistics datasets, are publicly available through the GWAS Catalog (). The lifetime smoking dataset is publicly accessible via its respective repository, as cited in the manuscript. The dataset related to inflammation, as described in the Methods section, was obtained from a third party and is not publicly available.
慢性呼吸道疾病（CRDs）和心血管疾病（cvd）是全球主要的健康负担。尽管常见，但由于重叠的症状和危险因素，CRD和CVD合并症经常被低估。因此，他们的关系仍然不清楚。目的和目的确定CRD和CVD之间的双向遗传关系，并探讨吸烟和炎症作为潜在的共同危险因素。方法采用双向孟德尔随机化（MR）研究crd与cvd的关系。从全基因组关联研究中检索了慢性阻塞性肺疾病（COPD）、哮喘、冠状动脉疾病（CAD）、心肌梗死（MI）、心力衰竭、心房颤动（AF）和缺血性脑卒中（IS）的汇总统计数据。我们进行了额外的分析，包括吸烟的单变量磁共振，吸烟调整的多变量磁共振和顺式磁共振来研究炎症标志物的作用。我们的MR分析发现CRD和CVD之间关系的遗传证据有限，反之亦然。然而，在哮喘和房颤风险增加之间观察到名义上显著的遗传关联（OR -方差加权（ORIVW） 1.036, 95% CI 1.003至1.070），在调整吸烟因素后仍然弱显著（ORIVW 1.040, 95% CI 1.008至1.074）。基因预测终生吸烟会大大增加所有CRD和CVD的风险。此外，基因代理的IL6R浓度与哮喘风险增加和CAD、MI、AF和IS风险降低相关，而IL1RN降低COPD风险，但增加CAD和MI风险。结论：虽然我们发现与CRD和CVD相关的遗传证据有限，但吸烟和炎症标志物通常对两者都有影响。这些发现突出了CRD-CVD合并症的复杂性，其病理生理可能不涉及彼此的直接因果关系。数据可以在一个公共的、开放访问的存储库中获得。数据可能会从第三方获得，并且不会公开提供。除两个汇总统计数据集外，本研究中使用的所有数据均可通过GWAS目录公开获取（）。终生吸烟数据集可通过其各自的存储库公开访问，如手稿中引用的那样。如方法部分所述，与炎症相关的数据集是从第三方获得的，不公开可用。
{"title":"Understanding the bidirectional relationship between chronic respiratory disease and cardiovascular disease using genetic evidence","authors":"Naesilla Naesilla, Jennifer K Quint, Verena Zuber","doi":"10.1136/thorax-2024-222908","DOIUrl":"https://doi.org/10.1136/thorax-2024-222908","url":null,"abstract":"Background Chronic respiratory diseases (CRDs) and cardiovascular diseases (CVDs) are leading global health burdens. Despite being common, CRD and CVD comorbidity is often underestimated due to overlapping symptoms and risk factors. Consequently, their relationship remains unclear. Aims and objectives To determine the bidirectional genetic relationship between CRD and CVD and explore smoking and inflammation as potentially shared joint risk factors. Methods We conducted bidirectional Mendelian randomisation (MR) to explore CRD–CVD relationships. Summary statistics from genome-wide association studies were retrieved for chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease (CAD), myocardial infarction (MI), heart failure, atrial fibrillation (AF) and ischaemic stroke (IS). We performed additional analysis including univariable MR for smoking, multivariable MR adjusting for smoking and cis-MR to investigate the role of inflammatory markers. Results Our MR analysis found limited genetic evidence of relationships between CRD and CVD, and vice versa. However, a nominally significant genetic association was observed between asthma and an increased risk of AF (OR inverse-variance weighted (ORIVW) 1.036, 95% CI 1.003 to 1.070), remaining weakly significant after adjusting for smoking (ORIVW 1.040, 95% CI 1.008 to 1.074). Genetically predicted lifetime smoking strongly increased all CRD and CVD risk. Additionally, genetically proxied IL6R concentration associated with increased asthma risk and decreased CAD, MI, AF and IS risk, while IL1RN decreased COPD risk but increased CAD and MI risk. Conclusions While we found limited genetic evidence linking CRD and CVD, smoking and inflammatory markers commonly affect both. These findings highlight the complexity of CRD–CVD comorbidities, whose pathophysiology likely does not involve direct causation of each other. Data are available in a public, open access repository. Data may be obtained from a third party and are not publicly available. All data used in this study, except for two summary statistics datasets, are publicly available through the GWAS Catalog (<https://www.ebi.ac.uk/gwas>). The lifetime smoking dataset is publicly accessible via its respective repository, as cited in the manuscript. The dataset related to inflammation, as described in the Methods section, was obtained from a third party and is not publicly available.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"59 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525138","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}
Pub Date : 2025-11-14DOI: 10.1136/thorax-2025-223095
Kenneth Verstraete, Iwein Gyselinck, Helene Huts, Remco Stuart Djamin, Michaël Staes, Sander Talman, Sarah Lindberg, Menno van der Eerden, Maarten De Vos, Wim Janssens
Objective: Long-term azithromycin treatment effectively prevents acute exacerbations of chronic obstructive pulmonary disease (COPD). However, patients would benefit from better identification of responders and non-responders to minimise unnecessary exposure. We aimed to assess treatment effect heterogeneity and estimate individual treatment effects (ITEs) to distinguish patients most likely to benefit from prophylactic treatment.
Methods: We used data from 1025 patients of the MACRO trial to assess the ITE of azithromycin on annual exacerbation rate. A Causal Forest was used as a causal machine learning model. We independently validated our findings using data from 83 patients of the COLUMBUS trial.
Results: The tertile of patients with the best predicted ITE within MACRO and within the COLUMBUS independent validation cohort showed significant and substantially greater reductions in annual exacerbation rates (in MACRO -0.50, rate ratio 0.70, p=0.01, in COLUMBUS: -2.28, rate ratio 0.43, p<0.001) compared with the average treatment effect across the entire cohort (MACRO -0.35, rate ratio 0.83, p=0.01 and COLUMBUS -1.28, rate ratio 0.58, p=0.001). Conversely, no significant treatment effect was observed in the remaining two-thirds of patients. Primary determinants of ITE included respiratory symptoms, white blood cell count, haemoglobin, C-reactive protein and forced vital capacity. Smoking status did not emerge as a significant predictor.
Conclusion: Based on five easily obtainable parameters to predict ITE, we identified treatment effect heterogeneity in COPD subjects treated with azithromycin maintenance therapy and found a small subgroup of responders driving the average reduction in exacerbations reported in previous trials.
{"title":"Identifying azithromycin responders with an individual treatment effect model in COPD.","authors":"Kenneth Verstraete, Iwein Gyselinck, Helene Huts, Remco Stuart Djamin, Michaël Staes, Sander Talman, Sarah Lindberg, Menno van der Eerden, Maarten De Vos, Wim Janssens","doi":"10.1136/thorax-2025-223095","DOIUrl":"10.1136/thorax-2025-223095","url":null,"abstract":"<p><strong>Objective: </strong>Long-term azithromycin treatment effectively prevents acute exacerbations of chronic obstructive pulmonary disease (COPD). However, patients would benefit from better identification of responders and non-responders to minimise unnecessary exposure. We aimed to assess treatment effect heterogeneity and estimate individual treatment effects (ITEs) to distinguish patients most likely to benefit from prophylactic treatment.</p><p><strong>Methods: </strong>We used data from 1025 patients of the MACRO trial to assess the ITE of azithromycin on annual exacerbation rate. A Causal Forest was used as a causal machine learning model. We independently validated our findings using data from 83 patients of the COLUMBUS trial.</p><p><strong>Results: </strong>The tertile of patients with the best predicted ITE within MACRO and within the COLUMBUS independent validation cohort showed significant and substantially greater reductions in annual exacerbation rates (in MACRO -0.50, rate ratio 0.70, p=0.01, in COLUMBUS: -2.28, rate ratio 0.43, p<0.001) compared with the average treatment effect across the entire cohort (MACRO -0.35, rate ratio 0.83, p=0.01 and COLUMBUS -1.28, rate ratio 0.58, p=0.001). Conversely, no significant treatment effect was observed in the remaining two-thirds of patients. Primary determinants of ITE included respiratory symptoms, white blood cell count, haemoglobin, C-reactive protein and forced vital capacity. Smoking status did not emerge as a significant predictor.</p><p><strong>Conclusion: </strong>Based on five easily obtainable parameters to predict ITE, we identified treatment effect heterogeneity in COPD subjects treated with azithromycin maintenance therapy and found a small subgroup of responders driving the average reduction in exacerbations reported in previous trials.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"900-908"},"PeriodicalIF":7.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1136/thorax-2025-223559
Elvin Atug, Franziska Christina Trudzinski, Angélique Holland, Christian Grah, Ralf-Harto Huebner, Franz Stanzel, Stephan Eggeling, Bernd Schmidt, Sylke Kurz, Stephan Eisenmann, Joanna Krist, Joachim Ficker, Björn Wiesemann, Wolfgang Gesierich, Ralf Eberhardt
Background Endoscopic lung volume reduction (ELVR) is increasingly used for treating patients with chronic obstructive pulmonary disease (COPD) and severe hyperinflation. Data on sex differences in ELVR outcomes are lacking, highlighting the need for detailed analysis. Methods This retrospective analysis examines sex-specific outcomes of ELVR with bronchoscopic valve placement using data from the German Lung Emphysema Registry (January 2017 to January 2025). Results The final analysis included 778 patients, 378 (47.2%) women, mean age 65.9±7.6 years. No significant differences in age or body mass index. At baseline, women had slightly better forced expiratory volume in 1 s (FEV1)% (31.4±8.5 vs 28.1±8.1, p<0.001) and vital capacity% (63.6±16.9 vs 59.2±14.8, p<0.001), but similar residual volume (RV)%. Men had higher rates of cardiovascular diseases, including coronary artery disease (20.9% vs 11.7%) and atrial fibrillation (7.3% vs 3.5%), p<0.05. Despite this, women reported a higher symptom burden with higher COPD Assessment Test (CAT) scores (25.9±6.1 vs 24.9±6.1, p<0.001), but similar St. George’s Respiratory Questionnaire (SGRQ) scores. Follow-up at 3 months for 574 patients showed no sex differences in ΔFEV1%, ΔRV% or Δdiffusing capacity of the lung for carbon monoxide%. Differences in treatment response were noted for ΔCAT score (−4.3±6.8 vs −1.9±6.1, p<0.001), ΔSGRQ (−13.2±17.3 vs −5.5±12.48, p<0.001), but not for dyspnoea. Multivariable analyses showed female sex (OR 1.89) as an independent predictor for SGRQ response, along with emphysema heterogeneity (OR 1.01) and pulmonary function response (ΔRV, OR 0.73). Conclusions Sex may not influence physiological outcomes but may impact symptom severity and quality of life, raising the question of whether sex should be considered when determining minimal clinically important differences in COPD. Data are available upon reasonable request.
内镜下肺减容术（ELVR）越来越多地用于治疗慢性阻塞性肺疾病（COPD）和严重恶性通货膨胀患者。缺乏关于ELVR结果的性别差异的数据，强调需要进行详细分析。回顾性分析使用德国肺气肿登记处（2017年1月至2025年1月）的数据，研究支气管镜下瓣膜置入术的ELVR的性别特异性结局。结果共纳入778例患者，其中女性378例（47.2%），平均年龄65.9±7.6岁。年龄和身体质量指数没有显著差异。在基线时，女性的1 s用力呼气量（FEV1）%（31.4±8.5 vs 28.1±8.1,p<0.001）和肺活量%（63.6±16.9 vs 59.2±14.8,p<0.001）稍好，但残余容积（RV）%相似。男性心血管疾病发生率更高，包括冠状动脉疾病（20.9% vs 11.7%）和房颤（7.3% vs 3.5%）， p<0.05。尽管如此，COPD评估测试（CAT）评分较高（25.9±6.1 vs 24.9±6.1,p<0.001），但圣乔治呼吸问卷（SGRQ）评分相似，女性报告的症状负担较高。对574例患者3个月的随访显示，在ΔFEV1%、ΔRV%或Δdiffusing肺部一氧化碳含量方面没有性别差异。ΔCAT评分差异（- 4.3±6.8 vs - 1.9±6.1,p<0.001）， ΔSGRQ评分差异（- 13.2±17.3 vs - 5.5±12.48,p<0.001），但呼吸困难无差异。多变量分析显示，女性性别（OR 1.89）、肺气肿异质性（OR 1.01）和肺功能反应（ΔRV, OR 0.73）是SGRQ反应的独立预测因子。性别可能不会影响生理结果，但可能影响症状严重程度和生活质量，这就提出了在确定COPD的最小临床重要差异时是否应考虑性别的问题。如有合理要求，可提供资料。
{"title":"Sex differences in outcome after endoscopic lung volume reduction (ELVR) in patients with emphysema: a retrospective analysis of the German Lung Emphysema Registry (LER e.V.)","authors":"Elvin Atug, Franziska Christina Trudzinski, Angélique Holland, Christian Grah, Ralf-Harto Huebner, Franz Stanzel, Stephan Eggeling, Bernd Schmidt, Sylke Kurz, Stephan Eisenmann, Joanna Krist, Joachim Ficker, Björn Wiesemann, Wolfgang Gesierich, Ralf Eberhardt","doi":"10.1136/thorax-2025-223559","DOIUrl":"https://doi.org/10.1136/thorax-2025-223559","url":null,"abstract":"Background Endoscopic lung volume reduction (ELVR) is increasingly used for treating patients with chronic obstructive pulmonary disease (COPD) and severe hyperinflation. Data on sex differences in ELVR outcomes are lacking, highlighting the need for detailed analysis. Methods This retrospective analysis examines sex-specific outcomes of ELVR with bronchoscopic valve placement using data from the German Lung Emphysema Registry (January 2017 to January 2025). Results The final analysis included 778 patients, 378 (47.2%) women, mean age 65.9±7.6 years. No significant differences in age or body mass index. At baseline, women had slightly better forced expiratory volume in 1 s (FEV1)% (31.4±8.5 vs 28.1±8.1, p<0.001) and vital capacity% (63.6±16.9 vs 59.2±14.8, p<0.001), but similar residual volume (RV)%. Men had higher rates of cardiovascular diseases, including coronary artery disease (20.9% vs 11.7%) and atrial fibrillation (7.3% vs 3.5%), p<0.05. Despite this, women reported a higher symptom burden with higher COPD Assessment Test (CAT) scores (25.9±6.1 vs 24.9±6.1, p<0.001), but similar St. George’s Respiratory Questionnaire (SGRQ) scores. Follow-up at 3 months for 574 patients showed no sex differences in ΔFEV1%, ΔRV% or Δdiffusing capacity of the lung for carbon monoxide%. Differences in treatment response were noted for ΔCAT score (−4.3±6.8 vs −1.9±6.1, p<0.001), ΔSGRQ (−13.2±17.3 vs −5.5±12.48, p<0.001), but not for dyspnoea. Multivariable analyses showed female sex (OR 1.89) as an independent predictor for SGRQ response, along with emphysema heterogeneity (OR 1.01) and pulmonary function response (ΔRV, OR 0.73). Conclusions Sex may not influence physiological outcomes but may impact symptom severity and quality of life, raising the question of whether sex should be considered when determining minimal clinically important differences in COPD. Data are available upon reasonable request.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"373 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499564","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}
Pub Date : 2025-11-13DOI: 10.1136/thorax-2025-224042
Max Olsson, Magnus Ekström
Breathlessness (breathing discomfort, dyspnoea)1 is the most common, distressing and limiting symptom in people with cardiorespiratory disease. Rising steeply in prevalence with age, the burden of breathlessness is large in the population, with as many as 10%–25% of people 40 years and older reporting breathlessness interfering with daily activities.2–4 Moreover, the prevalence of breathlessness is likely largely underestimated as people reduce their physical activity to avoid the symptom.5 Breathlessness is strongly associated with worse exercise limitation, physical and mental health,6 increased risks of hospitalisation and health utilisation,7 and with earlier death.8 9 A range of underlying conditions contributes to breathlessness in the population, including overweight and obesity, anxiety/stress, respiratory diseases (most notably asthma and chronic obstructive pulmonary disease (COPD)), deconditioning, depression and cardiac diseases—and conditions often coexist in the individual.3 10 However, breathlessness may often be underestimated11 and remain undetected (‘hidden’) during medical consultations,12 which could lead to delayed and insufficient management and worse outcomes.11 Evidence-based management of breathlessness includes non-pharmacological interventions such as cardiorespiratory rehabilitation training, breathing techniques, airflow to the face and upper airways using a hand-held fan, and multidisciplinary breathlessness services. A fundamental step in breathless management is to evaluate and diagnose underlying conditions contributing to the symptom (figure 1)—for optimised treatment of underlying …
{"title":"Time to diagnose and improve outcomes in people with breathlessness: a call for action","authors":"Max Olsson, Magnus Ekström","doi":"10.1136/thorax-2025-224042","DOIUrl":"https://doi.org/10.1136/thorax-2025-224042","url":null,"abstract":"Breathlessness (breathing discomfort, dyspnoea)1 is the most common, distressing and limiting symptom in people with cardiorespiratory disease. Rising steeply in prevalence with age, the burden of breathlessness is large in the population, with as many as 10%–25% of people 40 years and older reporting breathlessness interfering with daily activities.2–4 Moreover, the prevalence of breathlessness is likely largely underestimated as people reduce their physical activity to avoid the symptom.5 Breathlessness is strongly associated with worse exercise limitation, physical and mental health,6 increased risks of hospitalisation and health utilisation,7 and with earlier death.8 9 A range of underlying conditions contributes to breathlessness in the population, including overweight and obesity, anxiety/stress, respiratory diseases (most notably asthma and chronic obstructive pulmonary disease (COPD)), deconditioning, depression and cardiac diseases—and conditions often coexist in the individual.3 10 However, breathlessness may often be underestimated11 and remain undetected (‘hidden’) during medical consultations,12 which could lead to delayed and insufficient management and worse outcomes.11 Evidence-based management of breathlessness includes non-pharmacological interventions such as cardiorespiratory rehabilitation training, breathing techniques, airflow to the face and upper airways using a hand-held fan, and multidisciplinary breathlessness services. A fundamental step in breathless management is to evaluate and diagnose underlying conditions contributing to the symptom (figure 1)—for optimised treatment of underlying …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"173 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499569","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}
Pub Date : 2025-11-13DOI: 10.1136/thorax-2025-223536
Carl Reynolds, Jack Callum, Martie Van Tongeren
But for breathing, how much interstitial lung disease (ILD) would there be? Let us imagine we manage to ensure clean air, and only clean air, for everyone to breathe forever. Lung cancer and chronic obstructive pulmonary disease mortality would fall precipitously. How about ILD? The long-standing dogma of ILD has been inhaled environmental insult±genetic susceptibility → epithelial injury → dysregulated repair → disease. Significant progress has been made identifying important genetic susceptibility factors through genome-wide asssociation studies (GWAS). Certain causal environmental insults have been well characterised yet remain a significant problem. These include exposure to cigarette smoke, respirable crystalline silica and asbestos. The contribution of other potential environmental insults to the burden of ILD is less clear, though they have been estimated, for example, in the last joint American Thoracic Society/European Respiratory Society statement on the occupational burden of non-malignant respiratory disease.1 Little work to date has been done on gene-environment interaction for inhaled exposures in ILD. The paper by Lee et al ,2 ‘Inhalational Exposures Associated with Risk of Interstitial Lung Disease: A Systematic …
{"title":"Characterising the contribution of inhalational exposures in interstitial lung disease","authors":"Carl Reynolds, Jack Callum, Martie Van Tongeren","doi":"10.1136/thorax-2025-223536","DOIUrl":"https://doi.org/10.1136/thorax-2025-223536","url":null,"abstract":"But for breathing, how much interstitial lung disease (ILD) would there be? Let us imagine we manage to ensure clean air, and only clean air, for everyone to breathe forever. Lung cancer and chronic obstructive pulmonary disease mortality would fall precipitously. How about ILD? The long-standing dogma of ILD has been inhaled environmental insult±genetic susceptibility → epithelial injury → dysregulated repair → disease. Significant progress has been made identifying important genetic susceptibility factors through genome-wide asssociation studies (GWAS). Certain causal environmental insults have been well characterised yet remain a significant problem. These include exposure to cigarette smoke, respirable crystalline silica and asbestos. The contribution of other potential environmental insults to the burden of ILD is less clear, though they have been estimated, for example, in the last joint American Thoracic Society/European Respiratory Society statement on the occupational burden of non-malignant respiratory disease.1 Little work to date has been done on gene-environment interaction for inhaled exposures in ILD. The paper by Lee et al ,2 ‘Inhalational Exposures Associated with Risk of Interstitial Lung Disease: A Systematic …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"25 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499567","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}
Pub Date : 2025-11-09DOI: 10.1136/thorax-2025-223539
Gabriela Martins Costa Gomes,Adam M Collison,Wilfried J J Karmaus,Carla Rebeca Da Silva Sena,Vanessa E Murphy,Bronwyn K Brew,Tegan Grace,Paul D Robinson,Peter D Sly,Urs Frey,Philipp Latzin,Florian Wyler,Craig E Pennell,Peter G Gibson,Joerg Mattes
BACKGROUNDInfants of asthmatic mothers have reduced lung function in early life for reasons that remain to be defined. The association between inhaled corticosteroid (ICS) use during pregnancy and lung function in the offspring has not been investigated.OBJECTIVESTo investigate the association between ICS use during pregnancy and infant lung function.METHODSMultivariable regression analysis of infant lung function at 4-6 weeks (tidal breathing flow volume loops and functional residual capacity (FRC)) associated with use of ICS during pregnancy.RESULTSAmong infants born to asthmatic mothers, the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF:tE), corrected for end-expiratory lung volume (FRC), was improved in offsprings whose mothers used ICS during pregnancy compared with those who did not (n=161 ICS use vs n=25 no ICS use; coefficient 0.06 /mL, 95% CI 0.01 to 0.11, p=0.014). Compared with a control group of infants born to non-asthmatic mothers, there was a lower tPTEF:tE to FRC ratio in infants born to asthmatic mothers without ICS use (n=46 no asthma vs n=25 asthma no ICS use; coefficient -0.08 /mL, 95% CI -0.01 to -0.02, p=0.012) but not in infants born to asthmatic mothers with ICS use (n=46 no asthma vs n=161 asthma ICS use; coefficient -0.02 /mL, 95% CI -0.06 to 0.03, p=0.453).CONCLUSIONSThe association between maternal asthma and impaired infant lung function diminished in infants whose mothers used ICS during pregnancy.TRIAL REGISTRATIONAustralian New Zealand Clinical Trials Registry ACTRN12613000202763.
背景：哮喘母亲的孩子在早期肺功能下降，原因尚不明确。妊娠期间吸入皮质类固醇（ICS）使用与后代肺功能之间的关系尚未调查。目的探讨妊娠期使用ICS与婴儿肺功能的关系。方法对妊娠期间使用ICS与4-6周婴儿肺功能（潮汐呼吸流量容积循环和功能剩余容量（FRC））相关的多变量回归分析。结果在哮喘母亲所生的婴儿中，经呼气末肺容积（FRC）校正后，母亲在妊娠期间使用ICS的婴儿的呼气峰潮流量时间与呼气时间之比（tPTEF:tE）比未使用ICS的婴儿有所改善（n=161使用ICS vs n=25未使用ICS；系数0.06 /mL, 95% CI 0.01 ~ 0.11, p=0.014）。与非哮喘母亲所生婴儿的对照组相比，未使用ICS的哮喘母亲所生婴儿的tPTEF:tE与FRC之比较低（n=46无哮喘vs n=25哮喘未使用ICS；系数-0.08 /mL, 95% CI -0.01 ~ -0.02, p=0.012），但使用ICS的哮喘母亲所生婴儿的tPTEF:tE与FRC之比较低（n=46无哮喘vs n=161哮喘使用ICS；系数-0.02 /mL, 95% CI -0.06 ~ 0.03, p=0.453）。结论母亲在怀孕期间使用ICS的婴儿，其母亲哮喘与婴儿肺功能受损的相关性减弱。澳大利亚新西兰临床试验注册中心ACTRN12613000202763。
{"title":"Association between maternal asthma and impaired infant lung function is diminished by inhaled corticosteroid use in pregnancy.","authors":"Gabriela Martins Costa Gomes,Adam M Collison,Wilfried J J Karmaus,Carla Rebeca Da Silva Sena,Vanessa E Murphy,Bronwyn K Brew,Tegan Grace,Paul D Robinson,Peter D Sly,Urs Frey,Philipp Latzin,Florian Wyler,Craig E Pennell,Peter G Gibson,Joerg Mattes","doi":"10.1136/thorax-2025-223539","DOIUrl":"https://doi.org/10.1136/thorax-2025-223539","url":null,"abstract":"BACKGROUNDInfants of asthmatic mothers have reduced lung function in early life for reasons that remain to be defined. The association between inhaled corticosteroid (ICS) use during pregnancy and lung function in the offspring has not been investigated.OBJECTIVESTo investigate the association between ICS use during pregnancy and infant lung function.METHODSMultivariable regression analysis of infant lung function at 4-6 weeks (tidal breathing flow volume loops and functional residual capacity (FRC)) associated with use of ICS during pregnancy.RESULTSAmong infants born to asthmatic mothers, the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF:tE), corrected for end-expiratory lung volume (FRC), was improved in offsprings whose mothers used ICS during pregnancy compared with those who did not (n=161 ICS use vs n=25 no ICS use; coefficient 0.06 /mL, 95% CI 0.01 to 0.11, p=0.014). Compared with a control group of infants born to non-asthmatic mothers, there was a lower tPTEF:tE to FRC ratio in infants born to asthmatic mothers without ICS use (n=46 no asthma vs n=25 asthma no ICS use; coefficient -0.08 /mL, 95% CI -0.01 to -0.02, p=0.012) but not in infants born to asthmatic mothers with ICS use (n=46 no asthma vs n=161 asthma ICS use; coefficient -0.02 /mL, 95% CI -0.06 to 0.03, p=0.453).CONCLUSIONSThe association between maternal asthma and impaired infant lung function diminished in infants whose mothers used ICS during pregnancy.TRIAL REGISTRATIONAustralian New Zealand Clinical Trials Registry ACTRN12613000202763.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"100 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477744","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}
RATIONALEConventional bronchoscopy training often does not ensure lasting skill retention or adaptability to different anatomies, limiting real-world impact. This study used a digital-twin bronchoscopy simulator with various CT-derived bronchial tree models to better train novices.OBJECTIVESTo explore training with various anatomically diverse bronchial tree models in novices' bronchoscopy performance.METHODS60 bronchoscopy-naive participants were randomly assigned to three groups (n=20 each): control (written instruction only), anatomic-uniformity (trained on one standard bronchial model) and anatomic-variety (trained on multiple patient-derived bronchial models). All participants performed two tests: test 1 on a standard model and test 2 on a new CT-derived model. Both tests were repeated 3 months later to assess skill retention. The primary comparison was between the anatomic-variety and anatomic-uniformity groups.MEASUREMENTS AND MAIN RESULTS60 participants completed tests 1 and 2. 55 returned at 3 months. In test 1, there were no significant differences between the anatomic-variety and anatomic-uniformity groups in diagnostic completeness (DC, 0 segments, p=0.576), structured progress (SP, 1 correct progression, p=0.091) and procedure time (31 s, p=0.831). In test 2, the anatomic-variety group had significantly higher DC (2.5 segments, p<0.001) and SP (9 progression, p<0.001) than the anatomic-uniformity group. At 3 months, the anatomic-variety group retained superior DC and SP scores in both tests despite slight declines.CONCLUSIONSTraining with diverse anatomical models significantly enhanced bronchoscopy performance compared with repetitive practice on a single standardised model with partially maintained learning gains at 3 months.
{"title":"Digital twin-based bronchoscopy simulator improves training performance and skill retention of novices: a randomised controlled study.","authors":"Mingming Deng,Fajiu Li,Fei Tang,Wei Chen,Feng Wang,Chun-Li Tang,Run Tong,Zhen Yang,Weidong Xu,Nan Zhang,Yang Xia,Shiyue Li,Felix J F Herth,Gang Hou","doi":"10.1136/thorax-2025-223147","DOIUrl":"https://doi.org/10.1136/thorax-2025-223147","url":null,"abstract":"RATIONALEConventional bronchoscopy training often does not ensure lasting skill retention or adaptability to different anatomies, limiting real-world impact. This study used a digital-twin bronchoscopy simulator with various CT-derived bronchial tree models to better train novices.OBJECTIVESTo explore training with various anatomically diverse bronchial tree models in novices' bronchoscopy performance.METHODS60 bronchoscopy-naive participants were randomly assigned to three groups (n=20 each): control (written instruction only), anatomic-uniformity (trained on one standard bronchial model) and anatomic-variety (trained on multiple patient-derived bronchial models). All participants performed two tests: test 1 on a standard model and test 2 on a new CT-derived model. Both tests were repeated 3 months later to assess skill retention. The primary comparison was between the anatomic-variety and anatomic-uniformity groups.MEASUREMENTS AND MAIN RESULTS60 participants completed tests 1 and 2. 55 returned at 3 months. In test 1, there were no significant differences between the anatomic-variety and anatomic-uniformity groups in diagnostic completeness (DC, 0 segments, p=0.576), structured progress (SP, 1 correct progression, p=0.091) and procedure time (31 s, p=0.831). In test 2, the anatomic-variety group had significantly higher DC (2.5 segments, p<0.001) and SP (9 progression, p<0.001) than the anatomic-uniformity group. At 3 months, the anatomic-variety group retained superior DC and SP scores in both tests despite slight declines.CONCLUSIONSTraining with diverse anatomical models significantly enhanced bronchoscopy performance compared with repetitive practice on a single standardised model with partially maintained learning gains at 3 months.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"112 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477743","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}
Pub Date : 2025-11-07DOI: 10.1136/thorax-2025-223951
Anna Meffen, Dominick Shaw
Gabapentin and pregabalin (gabapentinoids) are medications that are commonly prescribed for neuropathic pain, and off label for chronic pain, fibromyalgia, general anxiety disorder, migraine and other chronic conditions1; their use globally rose significantly between 2008 and 2018.2 In 2017, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) issued an alert warning of a risk of severe respiratory depression in people using gabapentin with pre-existing poor respiratory function or neurological disease, renal impairment or concomitant use of central nervous system depressants. In 2019, both pregabalin and gabapentin were recategorised as controlled drugs because of their potential for abuse and risk of fatality, with a 300 mg gabapentin tablet worth approximately £1 on the street.3 A similar MHRA alert highlighting respiratory risks regarding pregabalin followed in 2021,4 and in 2020, the US Food and Drug Administration (FDA) issued an alert regarding the serious risk of breathing problems in patients receiving gabapentinoids based on data showing that patients with respiratory disease, including chronic obstructive pulmonary disease (COPD) or risk factors such as the use of other respiratory sedatives (including opioid pain medications), had a higher risk of respiratory depression and an increased risk of death with the use of gabapentin/pregabalin. Data were collated from both animal and human …
{"title":"Uncomfortably numb: the risk of respiratory depression from neuropathic pain medicines","authors":"Anna Meffen, Dominick Shaw","doi":"10.1136/thorax-2025-223951","DOIUrl":"https://doi.org/10.1136/thorax-2025-223951","url":null,"abstract":"Gabapentin and pregabalin (gabapentinoids) are medications that are commonly prescribed for neuropathic pain, and off label for chronic pain, fibromyalgia, general anxiety disorder, migraine and other chronic conditions1; their use globally rose significantly between 2008 and 2018.2 In 2017, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) issued an alert warning of a risk of severe respiratory depression in people using gabapentin with pre-existing poor respiratory function or neurological disease, renal impairment or concomitant use of central nervous system depressants. In 2019, both pregabalin and gabapentin were recategorised as controlled drugs because of their potential for abuse and risk of fatality, with a 300 mg gabapentin tablet worth approximately £1 on the street.3 A similar MHRA alert highlighting respiratory risks regarding pregabalin followed in 2021,4 and in 2020, the US Food and Drug Administration (FDA) issued an alert regarding the serious risk of breathing problems in patients receiving gabapentinoids based on data showing that patients with respiratory disease, including chronic obstructive pulmonary disease (COPD) or risk factors such as the use of other respiratory sedatives (including opioid pain medications), had a higher risk of respiratory depression and an increased risk of death with the use of gabapentin/pregabalin. Data were collated from both animal and human …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"1 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145455467","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}
Pub Date : 2025-11-05DOI: 10.1136/thorax-2024-222854
Jan Johnson, Simon R Johnson
Exercise-induced desaturation is poorly recognised in lymphangioleiomyomatosis (LAM) and its relationship to outcome is unknown. In a UK cohort study, 37% of 131 women with LAM experienced exercise-induced desaturation to <88% during a 6 min walk test. Forced expiratory volume in 1 s (FEV1) and DLCO were associated with walk parameters but had poor predictive accuracy for exercise-induced desaturation. A 5-year follow-up showed exercise-induced desaturation at baseline was associated with rapid FEV1 decline (p=0.008) and need for rapamycin treatment (p=0.00001). Women with LAM should be evaluated for exercise-induced desaturation to target ambulatory oxygen and improve identification of those at risk of poor outcomes.
{"title":"Prevalence and assessment of exercise-induced desaturation in lymphangioleiomyomatosis","authors":"Jan Johnson, Simon R Johnson","doi":"10.1136/thorax-2024-222854","DOIUrl":"https://doi.org/10.1136/thorax-2024-222854","url":null,"abstract":"Exercise-induced desaturation is poorly recognised in lymphangioleiomyomatosis (LAM) and its relationship to outcome is unknown. In a UK cohort study, 37% of 131 women with LAM experienced exercise-induced desaturation to <88% during a 6 min walk test. Forced expiratory volume in 1 s (FEV1) and DLCO were associated with walk parameters but had poor predictive accuracy for exercise-induced desaturation. A 5-year follow-up showed exercise-induced desaturation at baseline was associated with rapid FEV1 decline (p=0.008) and need for rapamycin treatment (p=0.00001). Women with LAM should be evaluated for exercise-induced desaturation to target ambulatory oxygen and improve identification of those at risk of poor outcomes.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"18 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447172","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}
Pub Date : 2025-11-04DOI: 10.1136/thorax-2025-223427
Lainey Perry Smith, Maree T Izatt, Geoffrey N Askin, Miriam P L Cameron
A 15-year-old girl presented to a paediatric emergency department with a 4-week history of frank haemoptysis. This was occurring weekly, increasing in volume to an episode of approximately one-third of a cup of fresh blood (80–100 mL). She had no cough between haemoptysis episodes and the blood did not appear to be mixed with sputum. She had a background of 22q deletion, attention deficit hyperactivity disorder (ADHD), anxiety, inflammatory bowel disease (IBD) and had been diagnosed with early-onset idiopathic scoliosis (EOIS) at age 10. After initial management with bracing, her severe right thoracic curve (T5–12) had progressed to 63°. Given her skeletal immaturity and premenarchal state, surgical options were discussed and vertebral body tethering (VBT) was selected. When the patient presented with haemoptysis, it was 3.5 years post surgery. VBT represents an emerging surgical technique used to treat …
{"title":"Haemoptysis in an adolescent post vertebral body tethering surgery for scoliosis","authors":"Lainey Perry Smith, Maree T Izatt, Geoffrey N Askin, Miriam P L Cameron","doi":"10.1136/thorax-2025-223427","DOIUrl":"https://doi.org/10.1136/thorax-2025-223427","url":null,"abstract":"A 15-year-old girl presented to a paediatric emergency department with a 4-week history of frank haemoptysis. This was occurring weekly, increasing in volume to an episode of approximately one-third of a cup of fresh blood (80–100 mL). She had no cough between haemoptysis episodes and the blood did not appear to be mixed with sputum. She had a background of 22q deletion, attention deficit hyperactivity disorder (ADHD), anxiety, inflammatory bowel disease (IBD) and had been diagnosed with early-onset idiopathic scoliosis (EOIS) at age 10. After initial management with bracing, her severe right thoracic curve (T5–12) had progressed to 63°. Given her skeletal immaturity and premenarchal state, surgical options were discussed and vertebral body tethering (VBT) was selected. When the patient presented with haemoptysis, it was 3.5 years post surgery. VBT represents an emerging surgical technique used to treat …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"29 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145441228","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}
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