Thorax最新文献

{"title":"1-year physical activity coaching programme in lung transplant recipients: an RCT","authors":"Sofie Breuls, Astrid Blondeel, Marieke Wuyts, Geert M Verleden, Robin Vos, Wim Janssens, Thierry Troosters, Heleen Demeyer","doi":"10.1136/thorax-2024-222896","DOIUrl":"https://doi.org/10.1136/thorax-2024-222896","url":null,"abstract":"Introduction Most lung transplant (LTX) recipients do not meet physical activity (PA) guidelines. Interventions are needed as long-term inactivity is related to morbidity and mortality. We investigated the effect of a telecoaching programme on objectively measured PA in LTX recipients. Methods Inactive patients (<7500 steps/day, n=90) were randomised into a light or intensive version of a 1-year PA telecoaching programme. The light intervention consisted of a step counter and a minimal version of the smartphone application. Patients randomised to the intensive intervention discussed PA barriers and goals, received a step counter, a patient-tailored smartphone application and supportive coaching calls. PA (primary outcome, assessed by an accelerometer), physical function, quality of life and symptoms were measured at baseline, after 3 months (primary endpoint) and 1 year. Mixed model analyses were used to investigate the effectiveness of the intervention compared with the light intervention. Results Between-group difference in change after 3 months and 1 year was observed as mean (CI) 750 (−96 to 1596) (p=0.08) and 680 (−244 to 1605) steps per day (p=0.15), 10 (−0.5 to 20) and 10 (−1 to 22) min of total moving time (walking, taking stairs and cycling) (both p=0.07) and −3 (−6 to 0) (p=0.07) and −6 (−10 to −2) (p=0.002) of sedentary time, all in favour of the intervention group. Other outcomes did not differ between groups. Conclusion PA tends to improve in LTX recipients by following an intensive telecoaching programme compared with a light programme. Trial registration number [NCT04122768][1]. Data are available upon reasonable request. Data cannot be shared publicly because of patient confidentiality according to the Belgian law. New analyses are available on reasonable request from the author or UZ Leuven ethical committee’ (ec@uzleuven.be). [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04122768&atom=%2Fthoraxjnl%2Fearly%2F2025%2F05%2F29%2Fthorax-2024-222896.atom","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"57 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adapting for the future: what can we learn from REMAP-CAP and COVID-19 pandemic trials?","authors":"Heather L Clark, Daniel Clark Files","doi":"10.1136/thorax-2025-223319","DOIUrl":"https://doi.org/10.1136/thorax-2025-223319","url":null,"abstract":"In this issue of Thorax , the REMAP-CAP investigators publish the final results from the COVID-19 Immune Modulation Therapy Domain for COVID-19 of Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).1 REMAP-CAP is an international, adaptive, platform trial focused on hospitalised patients with pneumonia. At the outset of the COVID-19 pandemic in early 2020, REMAP-CAP added a COVID-19 appendix to the existing master protocol to include investigational studies focused on hospitalised patients with COVID-19. The Immune Modulation Therapy Domain for COVID-19 evaluated two interleukin 6 (IL-6) receptor antagonists (tocilizumab and sarilumab), the IL-1 receptor antagonist anakinra and interferon β1a (IFN-β1a) against control (usual care) in an open-label design. The preliminary results from this Domain were previously published in the midst of the COVID-19 pandemic in April 2021.2 It included 353 patients in the tocilizumab arm, 48 in the sarilumab arm and 402 assigned to control. The report demonstrated that the IL-6 receptor antagonists improved both organ support-free days and mortality with posterior probabilities of over 99% compared with control. These results, along with those published by the RECOVERY group, established tocilizumab as a key therapeutic for severe COVID-19, and its use was …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"29 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung development genes, adult lung function and cardiovascular comorbidities","authors":"Laura Portas, Mohammad Talaei, Charlotte Dean, Nay Aung, Matthew David Hind, Alfred Pozarickij, Robin G Walters, China Kadoorie Biobank Collaborative Group, Peter GJ Burney, Steffen Petersen, Cosetta Minelli, Seif O Shaheen","doi":"10.1136/thorax-2024-222474","DOIUrl":"https://doi.org/10.1136/thorax-2024-222474","url":null,"abstract":"Background The association between lower adult lung function and increased cardiovascular comorbidity has not been adequately explained. We investigated whether shared developmental signalling pathways, critical to lung development and repair, could partly explain it. Methods In UK Biobank (UKB), we performed pairwise colocalisation analysis of variants in 55 lung development genes associated with adult forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1)/FVC, to see if these are also associated with coronary heart disease (CHD), blood pressure (systolic, diastolic, hypertension), pulse pressure, Arterial Stiffness index and carotid intima-media thickness. For CHD, we meta-analysed data from UKB and the CARDIoGRAM consortium. Results We found that 12 of the 55 genes shared the same variant between one (or more) lung function trait and one (or more) cardiovascular trait (H4colocalisation). The direction of effects was always in keeping with our hypothesis (lower lung function–higher cardiovascular risk) for FVC, but not always for FEV1/FVC. The seven signals for hypertension and CHD all replicated nominally in the FinnGen study, while replication was poor in the China Kadoorie Biobank (CKB) study. In addition, we found a further 10 genes where genetic associations with lung function and cardiovascular traits were within the same gene but involved different variants (H3 colocalisation). Interestingly, six of all 22 genes (H4 and H3 colocalisation) were novel for cardiovascular traits; four replicated in FinnGen, three in CKB. Conclusion Lung function and cardiovascular traits have shared developmental pathways that may partly explain why lower lung function, especially FVC, is associated with increased cardiovascular risk. Data are available on reasonable request. The data supporting the findings of this study are included in the manuscript and supplementary materials. Additional datasets and results can be shared on reasonable request to the corresponding author, subject to relevant ethical and data protection regulations.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"16 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial damage and ageing: the perfect storm","authors":"Richard J Hewitt, Laurence Pearmain, Elisavet Lyka, Jennifer Dickens","doi":"10.1136/thorax-2024-222060","DOIUrl":"https://doi.org/10.1136/thorax-2024-222060","url":null,"abstract":"Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease of lung parenchymal scarring that is triggered by repeated microinjury to a vulnerable alveolar epithelium. It is increasingly recognised that cellular ageing, whether physiological or accelerated due to telomere dysfunction, renders the epithelium less able to cope with injury and triggers changes in epithelial behaviour that ultimately lead to the development of disease. Aims This review aims to highlight how, with increasing age, the alveolar epithelium becomes vulnerable to exogenous insults. We discuss the downstream consequences of alveolar epithelial dysfunction on epithelial phenotype, alveolar repair and pro-pathogenic interactions with other alveolar niche-resident cell types which drive IPF pathogenesis. Narrative We highlight how a wide array of cellular mechanisms that maintain cellular homeostasis become dysfunctional with ageing. Waning replicative capacity, genomic stability, mitochondrial function, proteostasis and metabolic function all contribute to a phenotype of vulnerability to ‘second hits’. We discuss how in IPF the alveolar epithelium becomes dysfunctional, highlighting changes in repair capacity and fundamental cellular phenotype and how interactions between abnormal epithelium and other alveolar niche-resident cell types perpetuate disease. Conclusions The ageing epithelium is a vulnerable epithelium which, with the cumulative effects of environmental exposures, fundamentally changes its behaviour towards stalled differentiation, failed repair and profibrotic signalling. Further dissection of aberrant epithelial behaviour, and its impact on other alveolar cell types, will allow identification of novel therapeutic targets aimed at earlier pathogenic events.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"27 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"129Xe-MRI ventilation and acinar abnormalities highlight the significance of spirometric dysanapsis: findings from the NOVELTY ADPro UK substudy","authors":"Laurie J Smith, Helen Marshall, Demi Jakymelen, Alberto Biancardi, Guilhem J Collier, Ho-Fung Chan, Paul J C Hughes, Martin L Brook, Josh R Astley, Ryan Munro, Smitha Rajaram, Andrew J Swift, David Capener, Jody Bray, Jimmy E Ball, Oliver Rodgers, Bilal A Tahir, Madhwesha Rao, Graham Norquay, Nicholas D Weatherley, Leanne Armstrong, Latife Hardaker, Alberto Papi, Rod Hughes, Jim M Wild","doi":"10.1136/thorax-2024-222347","DOIUrl":"https://doi.org/10.1136/thorax-2024-222347","url":null,"abstract":"Rationale Airways dysanapsis is defined by CT or spirometry as a mismatch between the size of the airways and lung volume and is associated with increased risk of developing chronic obstructive pulmonary disease (COPD). Lung disease in participants with dysanapsis and a label of asthma and/or COPD remains poorly understood. Methods In participants with asthma and/or COPD, we used 129Xe-MRI to assess ventilation, acinar dimensions and gas exchange, and pulmonary function tests, and compared people with spirometric dysanapsis (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)<−1.64 z and FEV1>−1.64 z) to those with normal spirometry (FEV1, FVC and FEV1/FVC>−1.64 z). Results From 165 participants assessed in the NOVELTY (NOVEL observational longiTudinal studY) ADPro (advanced diagnostic profiling) study with a physician-assigned diagnosis of asthma and/or COPD, 43 had spirometric dysanapsis and were age-matched to 43 participants with normal spirometry. Participants with dysanapsis had significantly increased ventilation defects (median difference (md) (95% CI) = 4.0% (1.42% to 5.38%), p<0.001), ventilation heterogeneity (md (95% CI) = 2.56% (1.31% to 3.56%), p<0.001) and measures of acinar dimensions (md (95% CI) = 0.004 cm2.s−1 (0.0009 to 0.007), p=0.009) from 129Xe-MRI, than those with normal spirometry. At the 1-year follow-up, only participants with dysanapsis had a significant increase in ventilation defects (md (95% CI)=0.45% (0.09% to 2.1%),p=0.016). Lower FEV1/FVC in the dysanapsis cohort was associated with increased ventilation defects (r=−0.64, R2=0.41, p<0.001) and increased acinar dimensions (r=−0.52, R2=0.38, p<0.001), with the highest values seen in those with an FVC above the upper limit of normal. Conclusions Participants with asthma and/or COPD, presenting to primary care with spirometric dysanapsis, exhibited increased lung abnormalities on 129Xe-MRI, when compared with those with normal spirometry. Spirometric dysanapsis in asthma and/or COPD is therefore associated with significant lung disease, and the FEV1/FVC is related to the degree of airways abnormality on 129Xe-MRI. Data may be obtained from a third party and are not publicly available. De-identified participant data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data-sharing policy described at <https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure>. Data for studies directly listed on Vivli can be requested through Vivli at <https://vivli.org/>. Data for studies not listed on Vivli could be requested through Vivli at <https://vivli.org/members/enquiries-about-studies-not-listed-on-the-vivli-platform/>. AstraZeneca Vivli member page is also available outlining further details: <https://vivli.org/ourmember/astrazeneca/>. The NOVELTY protocol is available at <https://astrazenecagrouptrials.pharmacm.com>.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"19 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing heterogeneous treatment effects in acute care syndromes: principles and practical considerations","authors":"Fernando G Zampieri, Sean M Bagshaw, Alexandre B Cavalcanti","doi":"10.1136/thorax-2024-221989","DOIUrl":"https://doi.org/10.1136/thorax-2024-221989","url":null,"abstract":"Background Critical care medicine has historically relied on syndromic diagnoses such as sepsis, acute respiratory distress syndrome (ARDS) and acute kidney injury to guide research and treatment. While this approach has advanced clinical practice, the growing recognition of patient heterogeneity presents significant challenges for treatment optimisation and trial interpretation. Understanding heterogeneous treatment effects (HTE) has emerged as a crucial methodological frontier, particularly for complex critical care syndromes where patient responses to interventions vary substantially. Findings There are three major methodological frameworks for analysing HTE: (1) Risk-based analyses, guided by the Predictive Approaches to Treatment effect Heterogeneity statement, provide an accessible framework for examining treatment effect variation across baseline risk strata but may overlook important effect modifiers. (2) Clustering techniques have successfully identified distinct phenotypes in both ARDS and sepsis, though external validation remains challenging. (3) Effect-based methods employing new methods offer sophisticated capabilities for identifying treatment effect modifiers but require careful consideration to model specification. Conclusion This review examines these methodological approaches through both theoretical framework and practical application. Considerations on the applicability of HTE are also provided. We conclude that while HTE methods offer promising tools for personalising critical care interventions, their successful implementation requires careful consideration of both methodological rigour and practical feasibility.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"12 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-powered interpretation of lung function in interstitial lung diseases","authors":"Semra Bilaçeroğlu","doi":"10.1136/thorax-2025-223227","DOIUrl":"https://doi.org/10.1136/thorax-2025-223227","url":null,"abstract":"Artificial intelligence (AI) is a branch of computer science developed in the 1950s to imitate the human ability for solving complex problems. Currently, it is widely applied in various fields of medicine for diagnostic support, assistance with medical practice and drug discovery. After entering respiratory medicine two decades ago, AI has been used in this field to support in making diagnoses and predicting outcomes based on clinical data, imaging, pathology and pulmonary function tests (PFTs). Imaging is the field where AI has made the greatest progress in respiratory medicine.1–3 The current application areas of AI in interstitial lung disease (ILD), a complex group of disorders in respiratory medicine, are not few: drug discovery, risk assessment, decision-making for treatment, identifying cohort from databases, epidemiological analysis, medical assistance and support in interpreting imaging and other diagnostic tests.1 In the field of ILD, the increasing adoption of AI techniques owing to the complexities in ILD diagnosis and management has led to research primarily on AI-supported evaluation of imaging but also gene expression, imaging and genomic data, proteomic data and plasma biomarkers, volatile organic compounds and PFTs.4 Diagnosing ILD is challenging; it is often misdiagnosed initially or diagnosed late in the disease course as PFTs are only minimally affected at the onset. …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"24 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung cancer risk assessment by prediction model: a global perspective","authors":"Longyao Zhang, Xiang Wang, Qiuyuan Chen, Mengsheng Zhao, Can Ju, David C Christiani, Feng Chen, Ruyang Zhang, Yongyue Wei","doi":"10.1136/thorax-2023-221253","DOIUrl":"https://doi.org/10.1136/thorax-2023-221253","url":null,"abstract":"Background Numerous lung cancer risk prediction models have been developed and validated worldwide. It is imperative to offer a comprehensive overview and comparative analysis of their performances. Methods We conducted an extensive literature search to identify studies developing and/or validating lung cancer risk prediction models. Then we summarised and compared the external performance of these models, focusing on discriminative accuracy (C-index) and calibration performance (E:O ratio). Results After an initial screening of 10 210 articles, 35 studies on 21 distinct prediction models were identified, which used 42 different types of predictors spanning seven categories. Notable performance variations were observed in external validations. In North American cohorts, the C-index ranged from 0.60 to 0.87, with E:O ratios from 0.62 to 3.70. Among the European cohorts, the Trøndelag health study HUNT and CanPredict exhibited C-indices surpassing 0.870. Conversely, the Bach, lung cancer risk assessment tool (LCRAT), prostate, lung, colorectal and ovarian cancer screening (PLCO)m2012 and PLCOall2014 performed poorly in electronic health records of the Qresearch database subgroup, with C-indices falling below 0.60. PLCOm2012 reached the best E:O ratio of 1.00 (95% CI: 0.93 to 1.08) in the UK Biobank subgroup. In Asian cohorts, the C-index ranged from 0.54 to 0.87. Only three models, Korean Men, LCRAT and Liverpool lung project incidence risk model (LLPi), achieved a C-index exceeding 0.80. LCRAT demonstrated the best calibration, while Hoggart performed the worst. Conclusions Performance of lung cancer risk prediction models, despite being well developed and validated, varies in diverse populations. Significant regional imbalance persists in the development of these models. Rigorous external validation or recalibration study in the target population is crucial in accordance with the guidance prior to model implementation. PROSPERO registration number CRD42022324602. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"133 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking gun: when COPD therapies fail current smokers","authors":"Elsa Ben Hamou-Kuijpers, Simon Couillard","doi":"10.1136/thorax-2025-223459","DOIUrl":"https://doi.org/10.1136/thorax-2025-223459","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is mainly treated with bronchodilators (long-acting beta-agonists (LABA) and/or long-acting muscarinic antagonists (LAMA)) to reduce symptoms and exacerbations. Inhaled corticosteroids (ICS) are also frequently used, more recently in the form of single inhaler triple therapy (SITT).1–3 There are numerous established adverse effects of ICS (pneumonia, mycobacterial infection, cataracts, glaucoma, thrush, bruising, osteoporosis, adrenal insufficiency—and the list goes on),4 5 with more potent adverse outcomes (pulmonary embolism, cardiovascular disease, type 2 diabetes) having recently been reported in association with high-dose ICS in asthma.6 7 In view of the potential harms of ICS, the increasingly one-size-fits-all use of SITT in COPD1 8 is a growing concern which must be balanced against the therapeutic benefits of ICS (decreased exacerbations, improved lung function and, perhaps, decreased mortality/cardiovascular events).2 3 9 10 To better specify the place of ICS in COPD, it has been proposed to classify patients based on exacerbation rates and blood eosinophil counts.1 This may identify patients who would benefit from ICS, with higher blood eosinophil counts (ideally ≥0.3×109/L) acting as an important prognostic (predicting exacerbations/readmissions)11 and theragnostic (predicting responsiveness to ICS or type 2 targeting biologics) marker.2 3 12 Crucially, such stratification could avoid adverse effects of ICS in patients who experience no …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"34 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure–function–treatment relationships of aerosol deposition in patients with severe asthma","authors":"Omar Usmani, Sylvia Verbanck","doi":"10.1136/thorax-2025-223228","DOIUrl":"https://doi.org/10.1136/thorax-2025-223228","url":null,"abstract":"Inhaled aerosols, the cornerstone in the everyday therapeutic management of patients with asthma, target drug directly to their pathophysiological site of action within the lungs. Asthma is a disease of the whole airway tree1; that is, the central and peripheral airways, where the peripheral airways are considered a treatable trait.2 However, the complex architecture of the lungs with varied morphologic airway structures and disease pathologies results in variable, heterogeneous and patchy deposition patterns of inhaled drug. This leads to varying sensitivity from the multiple cell types targeted within the lungs, and the resultant therapeutic efficacy depends not only on drug pharmacology but also on the extent, site and degree of penetration of aerosol deposition in the airways.3 Radiolabelling of inhaled aerosols, coupled with direct in vivo lung imaging, has determined that smaller drug particles achieve deeper penetration into the lungs in patients with asthma.4 The study by Ragunayakam et al 5 forwards our understanding of structure–function–treatment relationships of inhaled corticosteroid (ICS) deposition and distribution in the lungs of patients with severe asthma, stratified by biomarkers of T2 inflammation. The authors assessed extrafine particles (<2 µm) of beclometasone compared with fine-particle fluticasone propionate (where CT-derived in silico airways modelling was used to predict ICS deposition in the lungs), with physiological, radiological and T2 inflammatory factors. Greater intrathoracic, central and peripheral airway deposition was observed with extrafine-particles compared with fine-particle ICS, confirming the …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"135 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113669","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}