Thorax最新文献

{"title":"CD206+ macrophages are relevant non-invasive imaging biomarkers and therapeutic targets in experimental lung fibrosis","authors":"Lenny Pommerolle, Guillaume Beltramo, Leo Biziorek, Marin Truchi, Alexandre Magno Maneschy Dias, Lucile Dondaine, Julie Tanguy, Nicolas Pernet, Victor Goncalves, Alexanne Bouchard, Marie Monterrat, Grégoire Savary, Nicolas Pottier, Kjetil Ask, Martin R J Kolb, Bernard Mari, Carmen Garrido, Bertrand Collin, Philippe Bonniaud, Olivier Burgy, Françoise Goirand, Pierre-Simon Bellaye","doi":"10.1136/thorax-2023-221168","DOIUrl":"https://doi.org/10.1136/thorax-2023-221168","url":null,"abstract":"Background Interstitial lung diseases (ILDs) include a large number of diseases associated with progressive pulmonary fibrosis (PPF), including idiopathic pulmonary fibrosis (IPF). Despite the rarity of each of the fibrotic ILDs individually, they cumulatively affect a considerable number of patients. PPF is characterised by an excessive collagen deposition leading to functional decline. Objectives Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression. CD206-expressing M2 macrophages are involved in fibrosis progression, and whether they may be relevant therapeutic targets or biomarkers remains an open question. Results In our study, CD206+ lung macrophages were monitored in bleomycin-induced lung fibrosis in mice by combining flow cytometry, scRNAseq and in vivo molecular imaging using a single photon emission computed tomography (SPECT) radiopharmaceutical, 99mTc-tilmanocept. The antifibrotic effect of the inhibition of M2 macrophage polarisation with a JAK inhibitor, tofacitinib, was assessed in vivo. We demonstrate that CD206-targeted in vivo SPECT imaging with 99mTc-tilmanocept was able to accurately detect and quantify the increase in CD206+ macrophages from early to advanced stages of experimental fibrosis and ex vivo in lung biopsies from patients with IPF. CD206-targeted imaging also specifically detected a decrease in CD206+ lung macrophages on nintedanib and tofacitinib treatment. Importantly, early in vivo imaging of CD206+ macrophages allowed the prediction of experimental lung fibrosis progression as well as nintedanib and tofacitinib efficacy. Conclusions These findings indicate that M2 macrophages may be relevant theranostic targets for personalised medicine for patients with PPF. Data are available upon reasonable request.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732677","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":"Non-cigarette tobacco products, aryl-hydrocarbon receptor repressor gene methylation and smoking-related health outcomes","authors":"Christina M Eckhardt, Pallavi Balte, Jack E Morris, Surya P Bhatt, David Couper, Jessica Fetterman, Neal Freedman, David R Jacobs, Lifang Hou, Ravi Kalhan, Yongmei Liu, Laura Loehr, Pamela L Lutsey, Joseph E Schwartz, Wendy White, Sachin Yende, Stephanie J London, Tiffany R Sanchez, Elizabeth C Oelsner","doi":"10.1136/thorax-2023-220731","DOIUrl":"https://doi.org/10.1136/thorax-2023-220731","url":null,"abstract":"Introduction Cigarette smoking leads to altered DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) gene. However, it remains unknown whether pipe or cigar smoking is associated with AHRR methylation. We evaluated associations of non-cigarette tobacco use with AHRR methylation and determined if AHRR methylation was associated with smoking-related health outcomes. Methods Data were pooled across four population-based cohorts that enrolled participants from 1985 to 2002. Tobacco exposures were evaluated using smoking questionnaires. AHRR cg05575921 methylation was measured in peripheral blood leucocyte DNA. Spirometry and respiratory symptoms were evaluated at the time of methylation measurements and in subsequent visits. Vital status was monitored using the National Death Index. Results Among 8252 adults (mean age 56.7±10.3 years, 58.1% women, 40.6% black), 4857 (58.9%) participants used cigarettes and 634 (7.7%) used non-cigarette tobacco products. Exclusive use of non-cigarette tobacco products was independently associated with lower AHRR methylation (−2.44 units, 95% CI −4.42 to −0.45), though to a lesser extent than exclusive use of cigarettes (−6.01 units, 95% CI −6.01 to −4.10). Among participants who exclusively used non-cigarette tobacco products, reduced AHRR methylation was associated with increased respiratory symptom burden (OR 1.60, 95% CI 1.03 to 2.68) and higher all-cause mortality (log-rank p=0.02). Conclusion Pipe and cigar smoking were independently associated with lower AHRR methylation in a multiethnic cohort of US adults. Among users of non-cigarette tobacco products, lower AHRR methylation was associated with poor respiratory health outcomes and increased mortality. AHRR methylation may identify non-cigarette tobacco users with an increased risk of adverse smoking-related health outcomes. Data are available on reasonable request.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732681","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":"Refractory granulomatous Pneumocystis jirovecii pneumonia masquerading as malignancy","authors":"Chi Wan Koo, Ananya Panda, Jennifer Boland Froemming","doi":"10.1136/thorax-2024-221457","DOIUrl":"https://doi.org/10.1136/thorax-2024-221457","url":null,"abstract":"An elderly female, lifelong non-smoker, with rheumatoid arthritis treated with methotrexate and prednisone for 10 years was referred for evaluation of incidentally detected, randomly distributed pulmonary nodules on a CT performed for pleuritic chest pain and dyspnoea (figure 1A). Subsequent [18F]fluoro-d-glucose (FDG)-positron emission tomography (PET) showed the nodules had increased in size and were FDG-avid (figure 1B). Patient underwent percutaneous biopsy at an external institution with pathology reported to be highly suspicious for lung adenocarcinoma. Figure 1 (A) CT angiogram performed for evaluation of pleuritic chest pain and dyspnoea demonstrated incidental solid, non-calcified left lower lobe subpleural predominant pulmonary nodules (arrow, additional nodules not shown). Note dependent atelectasis presenting as ground-glass opacities. (B) [18F]fluoro-d-glucose (FDG)-positron emission tomography performed 4 months later showed these nodules had more than doubled in size and were FDG-avid (arrow). No additional FDG avidity was detected elsewhere. After an unrevealing bronchoscopy with bronchoalveolar lavage, the patient was referred to our institution for further care. Re-evaluation of the previous percutaneous …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732678","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":"Unusual cause of trepopnea.","authors":"Suat Yee Lee, Juo-Hau Su, Chia-Chen Chang, Fatt Yang Chew","doi":"10.1136/thorax-2024-221844","DOIUrl":"https://doi.org/10.1136/thorax-2024-221844","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724584","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":"Integrated disease management: good news but more work to do.","authors":"Christine R Jenkins","doi":"10.1136/thorax-2024-221754","DOIUrl":"10.1136/thorax-2024-221754","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421087","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":"Respiratory rescue is the new frontier.","authors":"Sarath Ranganathan","doi":"10.1136/thorax-2024-221830","DOIUrl":"10.1136/thorax-2024-221830","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293770","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":"Quantifying sustained health system benefits of primary care-based integrated disease management for COPD: a 6-year interrupted time series study.","authors":"Christopher Licskai, Anna Hussey, Véronique Rowley, Madonna Ferrone, Zihang Lu, Kimball Zhang, Emilie Terebessy, Andrew Scarffe, Shannon Sibbald, Cathy Faulds, Tim O'Callahan, Teresa To","doi":"10.1136/thorax-2023-221211","DOIUrl":"10.1136/thorax-2023-221211","url":null,"abstract":"<p><strong>Background: </strong>Severe exacerbation of chronic obstructive pulmonary disease (COPD) is a trajectory-changing life event for patients and a major contributor to health system costs. This study evaluates the real-world impact of a primary care, integrated disease management (IDM) programme on acute health service utilisation (HSU) in the Canadian health system.</p><p><strong>Methods: </strong>Interrupted time series analysis using retrospective health administrative data, comparing monthly HSU event rates 3 years prior to and 3 years following the implementation of COPD IDM. Primary outcomes were COPD-related hospitalisation and emergency department (ED) visits. Secondary outcomes included hospital bed days and all-cause HSU.</p><p><strong>Results: </strong>There were 2451 participants. COPD-related and all-cause HSU rates increased in the 3 years prior to IDM implementation. With implementation, there was an immediate decrease (month 1) in COPD-related hospitalisation and ED visit rates of -4.6 (95% CI: -7.76 to -1.39) and -6.2 (95% CI: -11.88, -0.48) per 1000 participants per month, respectively, compared with the counterfactual control group. After 12 months, COPD-related hospitalisation rates decreased: -9.1 events per 1000 participants per month (95% CI: -12.72, -5.44) and ED visits -19.0 (95% CI: -25.50, -12.46). This difference nearly doubled by 36 months. All-cause HSU also demonstrated rate reductions at 12 months, hospitalisation was -10.2 events per 1000 participants per month (95% CI: -15.79, -4.44) and ED visits were -30.4 (95% CI: -41.95, -18.78).</p><p><strong>Conclusions: </strong>Implementation of COPD IDM in a primary care setting was associated with a changed trajectory of COPD-related and all-cause HSU from an increasing year-on-year trend to sustained long-term reductions. This highlights a substantial real-world opportunity that may improve health system performance and patient outcomes.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421088","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}

{"title":"Children’s interstitial lung disease (chILD): less rare than we thought?","authors":"Andrew Bush, Lawrence Nogee","doi":"10.1136/thorax-2024-221951","DOIUrl":"https://doi.org/10.1136/thorax-2024-221951","url":null,"abstract":"The presentation of childhood interstitial lung disease (chILD) is non-specific,1 and chILD is usually low on the list of diagnoses in children with combinations of respiratory symptoms, feeding difficulties and failure to thrive. However, if a diagnosis is not considered, it will never be made. In this issue of the Journal , Fletcher et al describe nearly 800 French children, suggesting that chILD may not be as rare as once thought.2 The French RespiRare network has long been systematically collecting incidence and prevalence data of rare diseases, and in this excellent publication, they report a chILD prevalence of 44/million children (95% CI 40.76 to 47.46) and thus a computed incidence of 4.4/million children (95% CI 3.44 to 5.56). This is similar to a recent Spanish study,3 and far greater than previous studies,4 5 which were likely underestimated due to incomplete ascertainment. The major strength of the present study is the collection of data from a well-organised network spanning the whole of France, with multiple different ways of ensuring chILDs were captured. Despite this, cases may still have been missed. For example, it is a surprise that they reported not a single ILD related to e-cigarettes.6 Newborns with rapidly progressive disease due to …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":10.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141631475","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":"Physical activity and body mass related to catch-up lung function growth in childhood: a population-based accelerated cohort study.","authors":"Sarah Koch, Gabriela Prado Peralta, Anne-Elie Carsin, Alicia Abellan, Celine Roda, Maties Torrent, Carmen Iñiguez, Ferran Ballester, Amparo Ferrero, Carlos Zabaleta, Aitana Lertxundi, Mònica Guxens, Martine Vrijheid, Jordi Sunyer, Maribel Casas, Judith Garcia-Aymerich","doi":"10.1136/thorax-2022-219666","DOIUrl":"10.1136/thorax-2022-219666","url":null,"abstract":"<p><strong>Objective: </strong>The existence of catch-up lung function growth and its predictors is uncertain. We aimed to identify lung function trajectories and their predictors in a population-based birth cohort.</p><p><strong>Methods: </strong>We applied group-based trajectory modelling to z-scores of forced expiratory volume in 1 second (zFEV₁) and z-scores of forced vital capacity (zFVC) from 1151 children assessed at around 4, 7, 9, 10, 11, 14 and 18 years. Multinomial logistic regression models were used to test whether potential prenatal and postnatal predictors were associated with lung function trajectories.</p><p><strong>Results: </strong>We identified four lung function trajectories: a low (19% and 19% of the sample for zFEV₁ and zFVC, respectively), normal (62% and 63%), and high trajectory (16% and 13%) running in parallel, and a catch-up trajectory (2% and 5%) with catch-up occurring between 4 and 10 years. Fewer child allergic diseases and higher body mass index z-score (zBMI) at 4 years were associated with the high and normal compared with the low trajectories, both for zFEV₁ and zFVC. Increased children's physical activity during early childhood and higher zBMI at 4 years were associated with the catch-up compared with the low zFEV₁ trajectory (relative risk ratios: 1.59 per physical activity category (1.03-2.46) and 1.47 per zBMI (0.97-2.23), respectively). No predictors were identified for zFVC catch-up growth.</p><p><strong>Conclusion: </strong>We found three parallel-running and one catch-up zFEV₁ and zFVC trajectories, and identified physical activity and body mass at 4 years as predictors of zFEV₁ but not zFVC catch-up growth.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050441","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":"Undertreating cardiovascular disease in people with chronic obstructive pulmonary disease (COPD).","authors":"Andrea S Gershon, Alina Blazer, Dennis Ko","doi":"10.1136/thorax-2023-221141","DOIUrl":"10.1136/thorax-2023-221141","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":null,"pages":null},"PeriodicalIF":9.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321715","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}