Christopher J. Ryerson

Background and Objective: This study determined contemporary transplant‐free survival in fibrotic interstitial lung disease (ILD), identified baseline factors associated with death or transplant, and assessed performance of the ILD‐GAP (Gender, Age, Physiology) index in a contemporary cohort. Methods: Patients with idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (fHP), connective tissue disease–associated ILD (CTD‐ILD), or unclassifiable ILD (uILD) prospectively enrolled in the Canadian Registry for Pulmonary Fibrosis were included. Transplant‐free survival at 1, 3, and 5 years was estimated overall and by subtype using enrollment as time zero. Cox proportional hazards models evaluated associations between patient characteristics and time to death or transplant. ILD‐GAP scores were calculated at 1, 2, and 3 years, and discriminability was assessed with Harrell's C statistic. Results: Among 4236 patients with fibrotic ILD enrolled in the Canadian Registry for Pulmonary Fibrosis (CARE‐PF), 31% had IPF, 40% CTD‐ILD, 9% fHP, and 20% uILD. Overall transplant‐free survival was 91% at 1 year, 72% at 3 years, and 57% at 5 years. Survival was lowest in IPF (87%, 61%, 39%) and highest in CTD‐ILD (95%, 81%, 70%). Compared with IPF, CTD‐ILD was associated with better 5‐year survival after adjustment (hazard ratio 0.64 [0.55–0.76]). ILD‐GAP showed moderate discrimination at 1 (C = 0.75), 2 (C = 0.74), and 3 years (C = 0.73). Conclusion: In this registry cohort anchored at enrollment, CTD‐ILD had superior transplant‐free survival versus IPF, and ILD‐GAP provided moderate prognostic accuracy.

Major changes in the 2025 update of the European Respiratory Society–American Thoracic Society Classification of Interstitial Pneumonias are presented from a radiologic perspective, highlighting the shift toward a more comprehensive radiologic-pathologic pattern-based classification.

Acute exacerbations (AEs) occur both in patients with idiopathic pulmonary fibrosis (IPF) and those with non-IPF fibrotic interstitial lung disease (fILD). These events confer high morbidity and mortality, with a lack of proven effective therapeutic interventions. The objective of this state-of-the-art document is to summarize latest evidence since the 2016 International Working Group Report on AE-IPF, expanding it across the spectrum of all fILDs. A comprehensive literature review on the epidemiology, associated and risk factors, prognosis, and management of AE-fILD is summarized. In addition to revising the AE definition and diagnostic criteria for broad application across different fILDs, a conceptual framework for acute respiratory worsening (ARW) has been proposed to encompass a variety of acute respiratory deteriorations, both related and unrelated to AEs. This allows structured evaluation in both clinical and research settings. The proposed revised definition for AE-fILD is an acute respiratory event characterized by increased respiratory symptoms or signs and associated with radiologic or histologic features consistent with diffuse alveolar damage (with or without superimposed organizing pneumonia) in a patient with known or newly diagnosed fILD. On the other hand, ARW refers to a heterogeneous group of clinical events with acute symptom worsening not attributable to diffuse alveolar damage in patients with fILD, such as pulmonary edema, bronchitis, and pneumonia, although severe pneumonia can trigger AE-fILD. Additionally, we discuss considerations for inclusion of AE as a clinical trial endpoint, as well as research priorities for advancing knowledge on the pathogenic mechanisms, event prediction, risk stratification, and development of drugs and supportive treatments.

A consensus classification for idiopathic interstitial pneumonias was first published in 2002, providing terminology for clinicians, radiologists and pathologists as well as highlighting that a multidisciplinary approach was best clinical practice. This comprised seven histological patterns that had corresponding idiopathic multidisciplinary diagnoses. This classification was updated in 2013, with the addition of an eighth histological pattern. Since 2013, there have been further advances in our understanding of interstitial pneumonias, in particular relating to idiopathic versus secondary disease, advances in molecular pathology and recognition of progressive pulmonary fibrosis (PPF), which have led to a further update in 2025. This review highlights the changes relevant to pathologists reporting interstitial pneumonias. Major changes include (1) expansion beyond idiopathic interstitial pneumonias to also include secondary causes, (2) subclassification as interstitial (fibrotic vs non‐fibrotic) and alveolar filling disorders, (3) expansion to include additional patterns (e.g. bronchiolocentric interstitial pneumonia), (4) improved terminology that better reflects histogenesis and (5) consideration of diagnostic confidence in biopsy evaluation. Pathologists also need to be aware of the advantages and limitations of cryobiopsy interpretation and the importance of reporting features that point towards a secondary cause rather than idiopathic disease. The 2025 classification provides a framework for a methodological approach to reporting biopsies in patients with interstitial pneumonia, which should be used prospectively for both diagnosis and research.

Anxiety and/or depression are common in fibrotic interstitial lung disease (ILD) but with unclear treatment implications. A prospective multicentre registry of 4009 patients was used to evaluate the association of depression and/or anxiety with clinical features and outcomes in fibrotic ILD. Anxiety and/or depression was associated with female sex and worse dyspnoea and cough but not lung function or ILD medication intolerance. Having anxiety and/or depression was associated with greater odds of patients declining referral for lung transplant assessment. Patients with anxiety and/or depression experience worse ILD symptoms and are more likely to decline referral for lung transplant assessment.

Background Currently available pharmacotherapies for interstitial lung disease (ILD) are limited to systemic glucocorticoids, steroid-sparing immunosuppressive medications and antifibrotic medications. Each of these treatments target major components of ILD biology. Objective This review presents the relevant evidence to the pharmacological management of ILD that is based on a treatable traits approach. We further highlight major knowledge gaps that should be the focus of future research that moves patient care toward a more precision-medicine approach. Summary of review The previous treatment paradigm for the pharmacotherapy of ILD is based on the integration of several clinical, laboratory, radiological and pathological features to an underlying biology that is more likely to respond to a given medication strategy. Patients with more acute presentations and suggestion of significant inflammation are typically treated with systemic glucocorticoid therapy, with the route and initial dose decided primarily based on the severity of disease. Patients with ILD who have chronic disease with suggestion of inflammatory features are typically treated with long-term steroid-sparing immunosuppression. Patients with ILD who have chronic disease with progressive fibrotic features are typically treated with antifibrotic medication. Emerging therapies include nerandomilast, a phosphodiesterase 4B inhibitor with antifibrotic and immunomodulatory effects that has recently been approved in the USA. A major goal is future integration of molecular endotypes to support a transition towards precision-based management of ILD. Conclusions Pharmacotherapy of ILD has previously focused on a morphology-based treatable traits approach that uses various clinical, laboratory, radiological and pathological clues to suggest a preferred treatment. We describe this approach and highlight specific questions that need to be addressed in future studies as we move toward a precision-based approach to patient management.