Thorax最新文献

{"title":"Assessing causal relationships between diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomisation study","authors":"Samuel T Moss, Cosetta Minelli, Olivia C Leavy, Richard J Allen, Nick Oliver, Louise V Wain, Gisli Jenkins, Iain Stewart","doi":"10.1136/thorax-2024-221472","DOIUrl":"https://doi.org/10.1136/thorax-2024-221472","url":null,"abstract":"Background Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung scarring. There is a known association between diabetes mellitus (DM) and IPF, but it is unclear whether a causal relationship exists between these traits. Objectives The objectives of this study are to examine causal relationships among DM, diabetes-associated traits and IPF using a Mendelian randomisation approach. Methods Two-sample MR approaches, including bidirectional inverse-variance weighted random effects and routine sensitivity models, used genetic variants identified from genome-wide association studies for type 1 diabetes (T1D), type 2 diabetes (T2D), glycated haemoglobin level (HbA1c), fasting insulin level and body mass index (BMI) to assess for causal effects of these traits on IPF. Further analyses using pleiotropy-robust and multivariable MR (MVMR) methods were additionally performed to account for trait complexity. Results Results did not suggest that either T1D (OR=1.00, 95% CI 0.93 to 1.07, p=0.90) or T2D (1.02, 0.93 to 1.11, p=0.69) are in the causal pathway of IPF. No effects were suggested of HbA1c (1.19, 0.63 to 2.22, p=0.59) or fasting insulin level (0.60, 0.31 to 1.15, p=0.12) on IPF, but potential effects of BMI on IPF were indicated (1.44, 1.12 to 1.85, p=4.00×10−3). Results were consistent in MVMR, although no independent effects of T2D (0.91, 0.68 to 1.21, p=0.51) or BMI (1.01, 0.94 to 1.09, p=0.82) on IPF were observed when modelled together. Conclusions This study suggests that DM and IPF are unlikely to be causally linked. This comorbid relationship may instead be driven by shared risk factors or treatment effects. Data are available upon reasonable request. Summary results for the GWAS of IPF susceptibility were requested through the collaborative genetic studies of idiopathic pulmonary fibrosis GitHub page: (<https://github.com/genomicsITER/PFgenetics>). Summary data for all other GWAS studies were retrieved from GWAS catalog (<https://www.ebi.ac.uk/gwas/>).","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"21 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752875","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":"Optimising bronchoalveolar lavage: lessons from alpha-1 antitrypsin deficiency","authors":"Malcolm Herron, Suzanne Roche, Daniel D Fraughen, Ronan C Heeney, Lasya Kanchi, Emma J Leacy, Michelle Casey, Cedric Gunaratnam, Tomás P Carroll, Mark P Murphy, Noel G McElvaney","doi":"10.1136/thorax-2024-221797","DOIUrl":"https://doi.org/10.1136/thorax-2024-221797","url":null,"abstract":"Background Bronchoalveolar lavage (BAL) is essential in determining the efficacy of novel therapies in alpha-1 antitrypsin deficiency (AATD). These require initial proof-of-concept demonstration that treatment administration increases alpha-1 antitrypsin (AAT) levels and/or anti-neutrophil elastase inhibitory capacity (ANEC) in the lung. Early-phase studies often encounter high interindividual variability of BAL results, primarily stemming from the inherent dilution characteristics of returned BAL fluid. A BAL protocol that minimises this variability is needed for reliable comparison of biochemical endpoints in the lung. Methods The study population included 21 severe AATD (ZZ), 22 moderate AATD (MZ) and 23 non-AATD (MM) individuals, further categorised as healthy, unobstructed current smokers or patients with chronic obstructive pulmonary disease (COPD). An additional six ZZ individuals were receiving intravenous alpha-1 augmentation therapy. We compared common BAL correction methods—albumin, total protein and epithelial lining fluid (ELF) volume measured by urea—when reporting early-phase biochemical endpoints, AAT and ANEC. Results BAL performed with a paediatric bronchoscope (PB) improved alveolar sampling compared with a traditional adult bronchoscope. Both uncorrected and ELF-corrected BAL demonstrated high interindividual variability regardless of lung health status. BAL total protein correction minimised interindividual variability, producing significant differences in AAT and ANEC between all genotypes, the strongest relationship with plasma AAT levels (r2=0.83), greatest inter-lobar concordance in AAT levels (r2=0.76) and strong correlation between BAL AAT and ANEC (r2=0.88). Conclusions By capitalising on the marked consistency in AAT levels between AAT genotypes, and the close relationship between plasma and lung AAT levels, we demonstrate reliable alveolar sampling that aligns closely with plasma. Data are available upon reasonable request.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"13 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712533","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":"Quantitative BAL: a suitable method for the assessment of epithelial lining fluid in alpha-1 antitrypsin deficiency?","authors":"David G Parr","doi":"10.1136/thorax-2024-221966","DOIUrl":"https://doi.org/10.1136/thorax-2024-221966","url":null,"abstract":"Measurements on biological fluids form the mainstay of routine clinical investigations. Samples of blood, urine, etc are, generally, easily obtainable and measurements can be interpreted directly. On the other hand, alveolar epithelial lining fluid (ELF) is relatively inaccessible but offers valuable insight into pathogenesis and pharmacokinetics relating to diseases affecting the alveolus. The lung is frequently described as having the surface area of a tennis court. When folded up to fit into the volume of an average thorax, it creates a complex maze that represents a significant obstacle to accessing ELF. The difficulty of gaining access safely and without disrupting the alveolar milieu is complicated by the delicate structure and function of the gas exchange membrane. Different approaches have been adopted including the use of a bronchoscopic microsample (PMS) probe,1 which allows direct measurements from ELF, or bronchoalveolar lavage (BAL), which requires a correction method to adjust for the dilutional effects of the lavage fluid. Urea (or albumin or creatinine) has been commonly used as an endogenous marker to estimate the volume of ELF2–5: by measuring the urea in BAL aspirate and plasma, a ratio can be calculated allowing an estimate of the dilution of apparent volume of ELF. ‘Contamination’ from lavage of the larger airways is also an issue that is influenced by the method of BAL sampling. This is not particularly important in routine clinical BAL, and guidelines do not stipulate the order of …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"66 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712593","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":"Neuropsychiatric side effects of montelukast: time to change prescribing practice?","authors":"David Lo, Jennifer K Quint","doi":"10.1136/thorax-2024-222643","DOIUrl":"https://doi.org/10.1136/thorax-2024-222643","url":null,"abstract":"Since 1998, montelukast has been licensed for the treatment of seasonal allergic rhinitis and asthma in people aged over 6 months. In children in particular, montelukast was welcomed as a steroid-sparing alternative to traditional asthma-preventer drugs, which could be taken just once daily, and which did not require the use of an inhaler. Although recent systematic reviews have shown regular inhaled corticosteroids (ICS) to be more effective than montelukast in controlling asthma symptoms, some children do demonstrate preferential response to montelukast.1 2 Consequently, current asthma guidelines still recommend montelukast as an optional alternative to ICS for mild-to-moderate asthma as monotherapy in children.3 While several studies and even prescribing information cite a wide range of potential neuropsychiatric side effects, the frequency of occurrence and exact nature of these side effects are not well defined and unfortunately not always well understood or recognised by healthcare professionals.4 In 2019 and then again in 2024, the UK Medicines and Healthcare products Regulatory Agency issued warnings and advice drawing attention to these problems.5 6 Similarly, in the USA, the Food and Drug Administration (FDA) issued a ‘black box warning’ for montelukast in 2020, drawing attention to documented mental and behavioural health risks associated with the use of the drug.7 More recently in 2024, the New York State district attorney called on the FDA to take urgent action to protect children from the risks of montelukast, including writing to …","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"2 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690944","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":"Neuropsychiatric diagnoses after montelukast initiation in paediatric patients with asthma","authors":"Tapio Paljarvi, Julian T Forton, Courtney Thompson, Sierra Luciano, Kimmo Herttua, Seena Fazel","doi":"10.1136/thorax-2024-221590","DOIUrl":"https://doi.org/10.1136/thorax-2024-221590","url":null,"abstract":"Background The evidence base on montelukast-associated adverse outcomes is inconclusive in children and young persons (CYP) with asthma. We aimed to investigate 1-year incidence of neuropsychiatric diagnoses after initiation of montelukast as an adjunct therapy to inhaled corticosteroids (ICSs) in CYP aged 3–17 years with asthma. Methods This propensity score matched cohort study was conducted using electronic health records between 2015 and 2019 in the TriNetX Analytics Network patient repository in the USA. Neuropsychiatric diagnoses were identified using the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. We estimated risk ratios (RRs), absolute risk increase (ARI) and number needed to harm (NNH) with 95% CIs. Findings The mean age (SD) at index prescription in the 107 384 CYP with asthma was 8.7 (4.0) years (93 461 (87%) mild to moderate asthma; 62 301 (58%) male; 53 485 (50%) white; 33 107 (31%) black/African American). Montelukast was associated with excess incidence of any neuropsychiatric outcome (71 per 1000 persons with montelukast and 54 per 1000 persons with no montelukast; RR 1.32 (95% CI 1.25 to 1.39); ARI per 100 persons, 1.71 (95% CI 1.44 to 1.98); 1-year NNH, 58 patients (95% CI 51 to 69)). The highest excess risk in the montelukast group was for sleep disorders (RR 1.63 (95% CI 1.50 to 1.77); ARI per 100 persons 1.17 (95% CI 1.00 to 1.33); NNH, 85 patients (95% CI 75 to 100)). Montelukast use was also associated with excess incidence of anxiety disorders (RR 1.16 (95% CI 1.08 to 1.24)) and mood disorders (RR 1.16 (95% CI 1.05 to 1.29)). Conclusions In CYP with asthma who were treated with ICSs, adjunct treatment with montelukast was associated with a higher incidence of neuropsychiatric outcomes compared with those who were not exposed to montelukast. Data may be obtained from a third party and are not publicly available. Data were provided by TriNetX (www.trinetx.com), a federated data network. Access to TriNetX’s deidentified patient data is available for the purpose of healthcare research with an approved user license.","PeriodicalId":23284,"journal":{"name":"Thorax","volume":"5 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690945","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":"A structural and metabolic framework for classifying pre-clinical tuberculosis infection phenotypes using 18F-FDG PET-CT: a prospective cohort analysis following <i>M. tuberculosis</i> exposure.","authors":"Jee Whang Kim, Sonam Vadera, Meedya Sharifpour, Amrita Bajaj, Anver Kamil, Pranabashis Haldar","doi":"10.1136/thorax-2024-221470","DOIUrl":"10.1136/thorax-2024-221470","url":null,"abstract":"<p><p>Tuberculosis (TB) control efforts are limited by ineffective characterisation of tuberculosis infection (TBI) -a heterogeneous spectrum of pre-clinical infection states, invisible to tools of routine clinical screening, that are associated with variable risk of progression to TB disease. In this prospective study, we use positron emission tomography-CT (PET-CT) as a high-resolution imaging modality to characterise and classify structural and metabolic features observed in 16 asymptomatic household TB contacts with normal chest radiographs. We identify four feature patterns that associate with distinct clinical and microbiological outcomes, supporting potential utility of PET-CT for objective classification of TBI phenotypes.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"1156-1159"},"PeriodicalIF":9.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447181","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":"Imaging in early tuberculosis.","authors":"Robert Wilkinson","doi":"10.1136/thorax-2024-221993","DOIUrl":"10.1136/thorax-2024-221993","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"1114-1115"},"PeriodicalIF":9.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576653","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":"Multiple lung cyst formation caused by metastatic bladder cancer.","authors":"Noriaki Nakagaki, Masashi Komori, Tatsuro Shimokama, Eiji Iwama","doi":"10.1136/thorax-2023-220573","DOIUrl":"10.1136/thorax-2023-220573","url":null,"abstract":"","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"1160-1161"},"PeriodicalIF":9.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354546","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":"Pulmonary fibrosis may begin in infancy: from childhood to adult interstitial lung disease.","authors":"Matthias Griese, Geoffrey Kurland, Michal Cidon, Robin R Deterding, Ralph Epaud, Nadia Nathan, Nicolaus Schwerk, David Warburton, Jason P Weinman, Lisa R Young, Gail H Deutsch","doi":"10.1136/thorax-2024-221772","DOIUrl":"10.1136/thorax-2024-221772","url":null,"abstract":"<p><strong>Background: </strong>Childhood interstitial lung disease (chILD) encompasses a group of rare heterogeneous respiratory conditions associated with significant morbidity and mortality. Reports suggest that many patients diagnosed with chILD continue to have potentially progressive or fibrosing disease into adulthood. Over the last decade, the spectrum of conditions within chILD has widened substantially, with the discovery of novel entities through advanced genetic testing. However, most evidence is often limited to small case series, with reports disseminated across an array of subspecialty, clinical and molecular journals. In particular, the frequency, management and outcome of paediatric pulmonary fibrosis is not well characterised, unlike in adults, where clear diagnosis and treatment guidelines are available.</p><p><strong>Methods and results: </strong>This review assesses the current understanding of pulmonary fibrosis in chILD. Based on registry data, we have provisionally estimated the occurrence of fibrosis in various manifestations of chILD, with 47 different potentially fibrotic chILD entities identified. Published evidence for fibrosis in the spectrum of chILD entities is assessed, and current and future issues in management of pulmonary fibrosis in childhood, continuing into adulthood, are considered.</p><p><strong>Conclusions: </strong>There is a need for improved knowledge of chILD among pulmonologists to optimise the transition of care from paediatric to adult facilities. Updated evidence-based guidelines are needed that incorporate recommendations for the diagnosis and management of immune-mediated disorders, as well as chILD in older children approaching adulthood.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":"1162-1172"},"PeriodicalIF":9.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996578","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":"Associations of pulmonary microvascular blood volume with per cent emphysema and CT emphysema subtypes in the community: the MESA Lung study.","authors":"Emilia A Hermann, Amin Motahari, Eric A Hoffman, Yifei Sun, Norrina Allen, Elsa D Angelini, Alain G Bertoni, David A Bluemke, Sarah E Gerard, Junfeng Guo, David W Kaczka, Andrew Laine, Erin Michos, Prashant Nagpal, James S Pankow, Coralynn S Sack, Benjamin Smith, Karen Hinckley Stukovsky, Karol E Watson, Artur Wysoczanski, R Graham Barr","doi":"10.1136/thorax-2024-222002","DOIUrl":"10.1136/thorax-2024-222002","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary microvasculature alterations are implicated in emphysema pathogenesis, but the association between pulmonary microvascular blood volume (PMBV) and emphysema has not been directly assessed at scale, and prior studies have used non-specific measures of emphysema.</p><p><strong>Methods: </strong>The Multi-Ethnic Study of Atherosclerosis Lung Study invited participants recruited from the community without renal impairment to undergo contrast-enhanced dual-energy CT. Pulmonary blood volume was calculated by material decomposition; PMBV was defined as blood volume in the peripheral 2 cm of the lung. Non-contrast CT was acquired to assess per cent emphysema and novel CT emphysema subtypes, which include the diffuse emphysema subtype and small-airways-related combined bronchitic-apical emphysema subtype. Generalised linear regression models included age, sex, race/ethnicity, body size, smoking, total lung volume and small airway count.</p><p><strong>Results: </strong>Among 495 participants, 53% were never-smokers and the race/ethnic distribution was 35% white, 31% black, 15% Hispanic and 18% Asian. Mean PMBV was 352±120 mL; mean per cent emphysema was 4.95±4.75%. Lower PMBV was associated with greater per cent emphysema (-0.90% per 100 mL PMBV, 95% CI: -1.29 to -0.51). The association was of larger magnitude in participants with 10 or more pack-years smoking and airflow obstruction, but present among participants with no smoking history or airflow limitation, and was specific to the diffuse CT emphysema subtype (-1.48% per 100 mL PMBV, 95% CI: -2.31 to -0.55).</p><p><strong>Conclusion: </strong>In this community-based study, lower PMBV was associated with greater per cent emphysema, including in participants without a smoking history or airflow limitation, and was specific to the diffuse CT emphysema subtype.</p>","PeriodicalId":23284,"journal":{"name":"Thorax","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576663","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}