BACKGROUNDAsbestos, mineral wool (MW), refractory ceramic fibres (RCF) and silica are among the most common exposures to mineral particles in the workplace.OBJECTIVETo study the effect of coexposure to asbestos and MW, crystalline silica or RCFs and the risk of lung cancer and mesothelioma.METHODSThe Asbestos-Related Diseases Cohort is a surveillance programme in retired workers exposed to asbestos during their working life. Complete job histories were collected and occupational exposure to asbestos was assessed by an expert, while occupational exposure to MW, RCFs and silica was assessed using French job-exposure matrices. Cox proportional hazards models were used to estimate HR and 95% CI for lung cancer mortality and lung cancer incidence and for mesothelioma mortality or mesothelioma incidence.RESULTSIn this population of workers exposed to asbestos, in the mortality study, exposures to MW, crystalline silica and RCFs were not found to be associated with lung cancer after adjustment for smoking and asbestos, nor with mesothelioma after adjustment for asbestos. In the incidence study, there was an association between exposure to crystalline silica (ever exposed) and mesothelioma (HRa=1.75, 95% CI 1.17 to 2.62).CONCLUSIONCrystalline silica is not known to induce mesothelioma but coexposure to asbestos could increase the effect of asbestos on the mesothelial cells.
石棉、矿棉（MW）、耐火陶瓷纤维（RCF）和二氧化硅是工作场所最常见的矿物颗粒暴露物。目的探讨石棉与MW、结晶二氧化硅或rcf共暴露对肺癌和间皮瘤发病的影响。方法石棉相关疾病队列是对工作期间接触石棉的退休工人的监测项目。收集了完整的工作经历，由专家评估了石棉的职业暴露，而使用法国工作暴露矩阵评估了MW， rcf和二氧化硅的职业暴露。使用Cox比例风险模型来估计肺癌死亡率和肺癌发病率以及间皮瘤死亡率或间皮瘤发病率的HR和95% CI。结果在死亡率研究中，暴露于MW、结晶二氧化硅和rcf与吸烟和石棉调整后的肺癌无关，也与石棉调整后的间皮瘤无关。在发病率研究中，暴露于结晶二氧化硅（曾经暴露）和间皮瘤之间存在关联（HRa=1.75, 95% CI 1.17至2.62）。结论结晶二氧化硅虽未诱发间皮瘤，但与石棉共暴露可增加间皮瘤对间皮瘤细胞的影响。
{"title":"Coexposure to asbestos, mineral wool, crystalline silica and refractory ceramic fibres and risk of lung cancer and mesothelioma.","authors":"Fleur Delva,Céline Gramond,Isabelle Thaon,Aude Lacourt,Patrick Brochard,Julia Benoist,Antoine Gislard,Francois Laurent,Christophe Paris,Pascal Andujar,Bénédicte Clin,Jean-Claude Pairon","doi":"10.1136/thorax-2024-222020","DOIUrl":"https://doi.org/10.1136/thorax-2024-222020","url":null,"abstract":"BACKGROUNDAsbestos, mineral wool (MW), refractory ceramic fibres (RCF) and silica are among the most common exposures to mineral particles in the workplace.OBJECTIVETo study the effect of coexposure to asbestos and MW, crystalline silica or RCFs and the risk of lung cancer and mesothelioma.METHODSThe Asbestos-Related Diseases Cohort is a surveillance programme in retired workers exposed to asbestos during their working life. Complete job histories were collected and occupational exposure to asbestos was assessed by an expert, while occupational exposure to MW, RCFs and silica was assessed using French job-exposure matrices. Cox proportional hazards models were used to estimate HR and 95% CI for lung cancer mortality and lung cancer incidence and for mesothelioma mortality or mesothelioma incidence.RESULTSIn this population of workers exposed to asbestos, in the mortality study, exposures to MW, crystalline silica and RCFs were not found to be associated with lung cancer after adjustment for smoking and asbestos, nor with mesothelioma after adjustment for asbestos. In the incidence study, there was an association between exposure to crystalline silica (ever exposed) and mesothelioma (HRa=1.75, 95% CI 1.17 to 2.62).CONCLUSIONCrystalline silica is not known to induce mesothelioma but coexposure to asbestos could increase the effect of asbestos on the mesothelial cells.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"94 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559110","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 : 2025-11-17DOI: 10.1136/thorax-2025-223991
Krunoslav Budimir, Kristina Juzbašić, Ivana Kuhtic, Robert Režan, Maja Hrabak Paar
A 58-year-old male was diagnosed with a right upper lobe lung adenocarcinoma, stage IIIA (T4 N1 M0). Based on the multidisciplinary team’s conclusion, the patient underwent neoadjuvant chemoimmunotherapy (nivolumab, carboplatin and paclitaxel) followed by surgery (right thoracotomy with right upper lobectomy, atypical middle lobe resection, partial resection of the fourth and fifth ribs and mediastinal lymph node dissection). On the first postoperative day, chest X-ray revealed an opacity in the right middle lobe (figure 1A), and 950 mL of haemorrhagic fluid was evacuated through the chest drain. Laboratory findings showed a slight haemoglobin drop to 106 g/L, along with mild leucocytosis (10.4×10⁹/L) and elevated C-reactive protein (136 mg/L). The patient remained afebrile. On the second postoperative day, a chest X-ray demonstrated complete consolidation of the middle lobe that obtained an oval-shaped configuration, accompanied by a right-sided pneumothorax, pneumomediastinum and subcutaneous emphysema (figure 1B). Figure 1 The initial postoperative chest radiograph, obtained on the first postoperative day in the supine position in the intensive care unit, demonstrated a focal opacity in the region of the middle lobe, without definitive features to suggest lobar torsion at that time (A). On the second postoperative day, follow-up chest radiography demonstrated radiographic progression, with complete consolidation of the oval-shaped middle lobe (M), accompanied by a right-sided pneumothorax, pneumomediastinum and subcutaneous emphysema of the chest wall (B). The right-sided chest …
{"title":"Postoperative lung middle lobe torsion: early recognition and diagnostic approach","authors":"Krunoslav Budimir, Kristina Juzbašić, Ivana Kuhtic, Robert Režan, Maja Hrabak Paar","doi":"10.1136/thorax-2025-223991","DOIUrl":"https://doi.org/10.1136/thorax-2025-223991","url":null,"abstract":"A 58-year-old male was diagnosed with a right upper lobe lung adenocarcinoma, stage IIIA (T4 N1 M0). Based on the multidisciplinary team’s conclusion, the patient underwent neoadjuvant chemoimmunotherapy (nivolumab, carboplatin and paclitaxel) followed by surgery (right thoracotomy with right upper lobectomy, atypical middle lobe resection, partial resection of the fourth and fifth ribs and mediastinal lymph node dissection). On the first postoperative day, chest X-ray revealed an opacity in the right middle lobe (figure 1A), and 950 mL of haemorrhagic fluid was evacuated through the chest drain. Laboratory findings showed a slight haemoglobin drop to 106 g/L, along with mild leucocytosis (10.4×10⁹/L) and elevated C-reactive protein (136 mg/L). The patient remained afebrile. On the second postoperative day, a chest X-ray demonstrated complete consolidation of the middle lobe that obtained an oval-shaped configuration, accompanied by a right-sided pneumothorax, pneumomediastinum and subcutaneous emphysema (figure 1B). Figure 1 The initial postoperative chest radiograph, obtained on the first postoperative day in the supine position in the intensive care unit, demonstrated a focal opacity in the region of the middle lobe, without definitive features to suggest lobar torsion at that time (A). On the second postoperative day, follow-up chest radiography demonstrated radiographic progression, with complete consolidation of the oval-shaped middle lobe (M), accompanied by a right-sided pneumothorax, pneumomediastinum and subcutaneous emphysema of the chest wall (B). The right-sided chest …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"17 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536476","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 : 2025-11-17DOI: 10.1136/thorax-2025-223940
Jordon Friedman, Ali Sadoughi
Lung cancer mortality has declined in recent years after decades of limited progress; however, it remains the leading cause of cancer-related deaths. This encouraging trend is partly attributed to earlier detection through the implementation of lung cancer screening programmes and the increasing identification of incidental lung nodules. These developments underscore the growing need to advance diagnostic capabilities and technologies for peripheral pulmonary lesions (PPLs).1–3 Significant investments and technological innovations in this area have led to the development of various diagnostic tools, including robotic bronchoscopy and real-time imaging techniques. These approaches aim to improve diagnostic yield via bronchoscopy while reducing complication rates, moving away from traditional transthoracic biopsy methods.4 As a result, these efforts have garnered substantial interest from clinicians, researchers and industry stakeholders. However, a single ‘best’ bronchoscopic technique has yet to be established. Many advanced technologies rely heavily on complementary or adjunctive tools to achieve optimal diagnostic performance. Examples of such technologies include but are not limited to radial endobronchial ultrasound, shape-sensing robotic bronchoscopy, electromagnetic navigation bronchoscopy, cone beam CT using both fixed and mobile systems, augmented fluoroscopy, confocal laser endomicroscopy and optical coherence tomography. Ongoing research is focused on integrating these modalities not only to enhance navigation accuracy to target lesions but also to …
{"title":"Peripheral airway balloon dilation: a standalone technique for lung nodule biopsy or just another tool in the armamentarium?","authors":"Jordon Friedman, Ali Sadoughi","doi":"10.1136/thorax-2025-223940","DOIUrl":"https://doi.org/10.1136/thorax-2025-223940","url":null,"abstract":"Lung cancer mortality has declined in recent years after decades of limited progress; however, it remains the leading cause of cancer-related deaths. This encouraging trend is partly attributed to earlier detection through the implementation of lung cancer screening programmes and the increasing identification of incidental lung nodules. These developments underscore the growing need to advance diagnostic capabilities and technologies for peripheral pulmonary lesions (PPLs).1–3 Significant investments and technological innovations in this area have led to the development of various diagnostic tools, including robotic bronchoscopy and real-time imaging techniques. These approaches aim to improve diagnostic yield via bronchoscopy while reducing complication rates, moving away from traditional transthoracic biopsy methods.4 As a result, these efforts have garnered substantial interest from clinicians, researchers and industry stakeholders. However, a single ‘best’ bronchoscopic technique has yet to be established. Many advanced technologies rely heavily on complementary or adjunctive tools to achieve optimal diagnostic performance. Examples of such technologies include but are not limited to radial endobronchial ultrasound, shape-sensing robotic bronchoscopy, electromagnetic navigation bronchoscopy, cone beam CT using both fixed and mobile systems, augmented fluoroscopy, confocal laser endomicroscopy and optical coherence tomography. Ongoing research is focused on integrating these modalities not only to enhance navigation accuracy to target lesions but also to …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"95 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532104","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}
Background Bronchoscopic limitations in reaching peripheral pulmonary lesions (PPLs) can compromise biopsy sensitivity, especially for small PPLs. Therefore, we developed the balloon dilatation for bronchoscope delivery (BDBD) technique to dilate bronchial pathways and facilitate bronchoscope advancement into the periphery. This study evaluated the diagnostic performance and safety profile of transbronchial biopsy using this technique. Methods This multicentre, single-arm, prospective study included patients with bronchus sign-positive PPLs measuring <20 mm. Bronchoscopy was performed using ultrathin or thin bronchoscopes under conscious sedation. When the bronchoscope could not advance further, the BDBD technique was used to approach closer to the target, followed by biopsies. The primary endpoint was the diagnostic sensitivity for malignancy in specimens obtained through the specified procedure, defined as bronchoscope advancement using balloon dilatation, direct biopsy site visualisation and absence of serious adverse events. Results Eighteen of 22 patients who underwent bronchoscopy with the BDBD technique were ultimately diagnosed with cancer. BDBD enabled bronchoscope advancement in all 18 cases without serious complications, allowed direct biopsy site visualisation in 17 and detected cancer in 14. Thus, the diagnostic sensitivity for malignancy was 77.8% (14/18). Beyond these cases, one patient who met all procedural criteria was diagnosed with cryptococcosis. Another patient was diagnosed with cancer without direct visualisation. On average, BDBD enabled bronchoscope advancement by 2.3 bifurcations. Conclusion In this small observational study, BDBD appeared to be a promising technique for improving the diagnostic sensitivity of bronchoscopy for small PPLs. Further validation is necessary in large cohorts. Trial registration number jRCT2052220174 Data are available upon reasonable request. The data that support the findings of this study and the original study protocol are available from the corresponding author (KM) on reasonable request.
{"title":"Balloon dilatation for bronchoscope delivery: first-in-human trial of a novel technique for peripheral lung field access","authors":"Kotaro Miyake, Masahide Oki, Hidekazu Suzuki, Hideo Saka, Shinji Sasada, Norio Okamoto, Tatsuya Imabayashi, Yoshihito Kogure, Takayuki Shiroyama, Haruhiko Hirata, Izumi Nagatomo, Yoshito Takeda, Atsushi Kumanogoh","doi":"10.1136/thorax-2025-223218","DOIUrl":"https://doi.org/10.1136/thorax-2025-223218","url":null,"abstract":"Background Bronchoscopic limitations in reaching peripheral pulmonary lesions (PPLs) can compromise biopsy sensitivity, especially for small PPLs. Therefore, we developed the balloon dilatation for bronchoscope delivery (BDBD) technique to dilate bronchial pathways and facilitate bronchoscope advancement into the periphery. This study evaluated the diagnostic performance and safety profile of transbronchial biopsy using this technique. Methods This multicentre, single-arm, prospective study included patients with bronchus sign-positive PPLs measuring <20 mm. Bronchoscopy was performed using ultrathin or thin bronchoscopes under conscious sedation. When the bronchoscope could not advance further, the BDBD technique was used to approach closer to the target, followed by biopsies. The primary endpoint was the diagnostic sensitivity for malignancy in specimens obtained through the specified procedure, defined as bronchoscope advancement using balloon dilatation, direct biopsy site visualisation and absence of serious adverse events. Results Eighteen of 22 patients who underwent bronchoscopy with the BDBD technique were ultimately diagnosed with cancer. BDBD enabled bronchoscope advancement in all 18 cases without serious complications, allowed direct biopsy site visualisation in 17 and detected cancer in 14. Thus, the diagnostic sensitivity for malignancy was 77.8% (14/18). Beyond these cases, one patient who met all procedural criteria was diagnosed with cryptococcosis. Another patient was diagnosed with cancer without direct visualisation. On average, BDBD enabled bronchoscope advancement by 2.3 bifurcations. Conclusion In this small observational study, BDBD appeared to be a promising technique for improving the diagnostic sensitivity of bronchoscopy for small PPLs. Further validation is necessary in large cohorts. Trial registration number jRCT2052220174 Data are available upon reasonable request. The data that support the findings of this study and the original study protocol are available from the corresponding author (KM) on reasonable request.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"62 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532096","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 : 2025-11-15DOI: 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}
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