Question addressed by the study: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD.Methods: Through a case–control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.Results: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24–0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19–0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26–0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001).Answer to the question: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Background: The 2013 American Thoracic Society/European Respiratory Society Statement on the classification of the idiopathic interstitial pneumonias described 6 major and 2 rare subtypes of idiopathic interstitial pneumonia, as well as recognising unclassifiable disease. Objective: The objective of this statement is to update the 2013 classification of interstitial pneumonia. Methods: Five co-chairs identified a committee of 32 experts in the field as well as two individuals with lived experience. Creation of the document was supported by a series of video meetings, first including the full committee and then subgroups assigned to draft specific sections of the document. The classification scheme was developed by consensus. Results: The multidisciplinary committee of experts identified four major advances to the classification of interstitial pneumonia: (1) expansion beyond idiopathic interstitial pneumonias to also include secondary causes; (2) identification of new subcategories and updated terms, including addition of bronchiolocentric interstitial pneumonia as a major pattern as well as changing from acute interstitial pneumonia to idiopathic diffuse alveolar damage and desquamative interstitial pneumonia to alveolar macrophage pneumonia; (3) subclassification of interstitial and alveolar filling disorders, with interstitial disorders further subclassified as fibrotic versus non-fibrotic; and (4) consideration of diagnostic confidence in patient evaluation and management. The committee also provided a comprehensive update on the status of potential molecular tools and identified future research priorities. Conclusions: This update builds upon the previous classification approach by describing major advances in the classification of interstitial pneumonia over the last decade.

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA’s ‘feels, functions, survives’ criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include ‘feels, functions, survives’ measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences—namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients’ quality of life and survival.

This report is based on proceedings from the Exposure Assessment Tools for Hypersensitivity Pneumonitis (HP) Workshop, sponsored by the American Thoracic Society, that took place on May 18, 2019, in Dallas, Texas. The workshop was initiated by members from the Environmental, Occupational, and Population Health and Clinical Problems Assemblies of the American Thoracic Society. Participants included international experts from pulmonary medicine, occupational medicine, radiology, pathology, and exposure science. The meeting objectives were to 1) define currently available tools for exposure assessment in evaluation of HP, 2) describe the evidence base supporting the role for these exposure assessment tools in HP evaluation, 3) identify limitations and barriers to each tool's implementation in clinical practice, 4) determine which exposure assessment tools demonstrate the best performance characteristics and applicability, and 5) identify research needs for improving exposure assessment tools for HP. Specific discussion topics included history-taking and exposure questionnaires, antigen avoidance, environmental assessment, specific inhalational challenge, serum-specific IgG testing, skin testing, lymphocyte proliferation testing, and a multidisciplinary team approach. Priorities for research in this area were identified.

Sex and gender differences influence key domains of research, lung health, healthcare access and healthcare delivery. In interstitial lung diseases (ILDs), mouse models of pulmonary fibrosis are clearly influenced by sex hormones. Additionally, short telomeres, a biomarker of telomere regulation gene mutations, are impacted by sex, while heritability unexplained by genetic variation may be attributable to gendered environmental factors that drive epigenetic control. Diseases like idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, occupational ILDs, connective tissue-associated ILDs and lymphangioleiomyomatosis have different prevalence and prognosis between men and women. These differences arise from a complex interplay between biological sex and sociocultural gender influencing genetics, epigenomic modifiers, hormones, immune function, response to treatment and interaction with healthcare systems. Much work remains to be done to systematically integrate sex and gender analysis into relevant domains of science and clinical care in ILD, from strategic considerations for establishing research priorities to guidelines for establishing best clinical practices. Accounting for sex and gender in ILD is essential to the practice of individualised, patient-centred medicine.