Brintha Selvarajah, Amyn Bhamani, Mehran Azimbagirad, Burcu Ozaltin, Ryoko Egashira, Daisuke Yamuda, John McCabe, Nicola Smallcombe, Priyam Verghese, Ruth Prendecki, Andrew Creamer, Jennifer L Dickson, Carolyn Horst, Sophie Tisi, Helen Hall, Chuen R Khaw, Monica L Mullin, Kylie Gyertson, Anne-Marie Hacker, Laura Farrelly, Anand Devaraj, Arjun Nair, Mariia Yuneva, Neal Navani, Daniel C Alexander, Rachel Clare Chambers, Joanna Porter, Allan Hackshaw, Gisli Jenkins, Sam M Janes, Joseph Jacob
{"title":"Differentiating clinically important interstitial lung abnormalities in lung cancer screening.","authors":"Brintha Selvarajah, Amyn Bhamani, Mehran Azimbagirad, Burcu Ozaltin, Ryoko Egashira, Daisuke Yamuda, John McCabe, Nicola Smallcombe, Priyam Verghese, Ruth Prendecki, Andrew Creamer, Jennifer L Dickson, Carolyn Horst, Sophie Tisi, Helen Hall, Chuen R Khaw, Monica L Mullin, Kylie Gyertson, Anne-Marie Hacker, Laura Farrelly, Anand Devaraj, Arjun Nair, Mariia Yuneva, Neal Navani, Daniel C Alexander, Rachel Clare Chambers, Joanna Porter, Allan Hackshaw, Gisli Jenkins, Sam M Janes, Joseph Jacob","doi":"10.1136/bmjresp-2025-003298","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung abnormalities (ILAs) are common incidental findings in lung cancer screening (LCS). However, challenges remain in identifying clinically relevant ILAs as highlighted in a joint statement by a European multidisciplinary task force led by the European Respiratory Society (ERS). To address these challenges, we analysed ILAs identified in one of Europe's largest LCS studies.</p><p><strong>Methods: </strong>Of 11 635 LCS individuals, 417 screen-detected ILAs were evaluated using a new visual classification system focused on traction bronchiolectasis: non-fibrotic ILA (no traction bronchiolectasis), fibrotic ILA (traction bronchiolectasis in ≤2 lobes); undiagnosed interstitial lung disease (traction bronchiolectasis in >2 lobes). Observer agreement was compared with Fleischner Society ILA classification using Cohen's Kappa. An age, sex and smoking history-matched control group allowed the examination of associations between baseline ILA/UILD and comorbidities, forced vital capacity (FVC), hospitalisations (Student's t-tests) and mortality (univariable and multivariable Cox proportional hazards models).</p><p><strong>Findings: </strong>Our visual ILA classification showed superior interobserver agreement (K=0.76) versus the Fleischner ILA classification (K=0.64). ILA/UILD subjects had more prevalent comorbidities, increasing (vs controls) approximately 10 years prior to ILA/UILD diagnosis. Compared with controls, mortality rates were 6-fold higher for UILD participants and 3-fold higher for fibrotic and non-fibrotic ILA subtypes. On multivariable Cox regression analysis, ILA/UILD presence (HR=4.90, 95% CI =2.36 to 10.10, p<0.001) showed stronger independent associations with mortality than baseline FVC (HR=0.98, 95% CI =0.96 to 1.00, p=0.04).</p><p><strong>Conclusion: </strong>We demonstrate a new reproducible classification of clinically important ILA/UILDs in LCS populations. We highlight that FVC shows limited associations with mortality in ILA/UILD subjects. Increased multiorgan comorbidity in ILA/UILD subjects highlights a need for comprehensive early multisystem evaluation.</p>","PeriodicalId":9048,"journal":{"name":"BMJ Open Respiratory Research","volume":"12 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Respiratory Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/bmjresp-2025-003298","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Interstitial lung abnormalities (ILAs) are common incidental findings in lung cancer screening (LCS). However, challenges remain in identifying clinically relevant ILAs as highlighted in a joint statement by a European multidisciplinary task force led by the European Respiratory Society (ERS). To address these challenges, we analysed ILAs identified in one of Europe's largest LCS studies.
Methods: Of 11 635 LCS individuals, 417 screen-detected ILAs were evaluated using a new visual classification system focused on traction bronchiolectasis: non-fibrotic ILA (no traction bronchiolectasis), fibrotic ILA (traction bronchiolectasis in ≤2 lobes); undiagnosed interstitial lung disease (traction bronchiolectasis in >2 lobes). Observer agreement was compared with Fleischner Society ILA classification using Cohen's Kappa. An age, sex and smoking history-matched control group allowed the examination of associations between baseline ILA/UILD and comorbidities, forced vital capacity (FVC), hospitalisations (Student's t-tests) and mortality (univariable and multivariable Cox proportional hazards models).
Findings: Our visual ILA classification showed superior interobserver agreement (K=0.76) versus the Fleischner ILA classification (K=0.64). ILA/UILD subjects had more prevalent comorbidities, increasing (vs controls) approximately 10 years prior to ILA/UILD diagnosis. Compared with controls, mortality rates were 6-fold higher for UILD participants and 3-fold higher for fibrotic and non-fibrotic ILA subtypes. On multivariable Cox regression analysis, ILA/UILD presence (HR=4.90, 95% CI =2.36 to 10.10, p<0.001) showed stronger independent associations with mortality than baseline FVC (HR=0.98, 95% CI =0.96 to 1.00, p=0.04).
Conclusion: We demonstrate a new reproducible classification of clinically important ILA/UILDs in LCS populations. We highlight that FVC shows limited associations with mortality in ILA/UILD subjects. Increased multiorgan comorbidity in ILA/UILD subjects highlights a need for comprehensive early multisystem evaluation.
期刊介绍:
BMJ Open Respiratory Research is a peer-reviewed, open access journal publishing respiratory and critical care medicine. It is the sister journal to Thorax and co-owned by the British Thoracic Society and BMJ. The journal focuses on robustness of methodology and scientific rigour with less emphasis on novelty or perceived impact. BMJ Open Respiratory Research operates a rapid review process, with continuous publication online, ensuring timely, up-to-date research is available worldwide. The journal publishes review articles and all research study types: Basic science including laboratory based experiments and animal models, Pilot studies or proof of concept, Observational studies, Study protocols, Registries, Clinical trials from phase I to multicentre randomised clinical trials, Systematic reviews and meta-analyses.