The 2025 update to the classification of the interstitial pneumonias presents multiple important advances. The objective of this "Guidelines in Context" document is to review the recent European Respiratory Society (ERS)/American Thoracic Society (ATS) Statement on the Classification of the Interstitial Pneumonias. The most notable advances are the inclusion of idiopathic and secondary disorders in a single adaptable classification framework, distinction between morphologic pattern and multidisciplinary diagnosis, terminology that better represents biology and morphology, identification of clinically relevant subgroups, and establishment of diagnostic confidence for both morphologic pattern and multidisciplinary diagnosis. We encourage readers to familiarize themselves with these updates and incorporate these advances to help support further improvements in patient care and further our understanding of these complex disorders. La mise & agrave; jour de 2025 de la classification des pneumonies interstitielles comporte plusieurs avanc & eacute;es importantes. L'objectif du pr & eacute;sent document, intitul & eacute; & laquo; Lignes directrices en contexte & raquo;, est de passer en revue la r & eacute;cente d & eacute;claration de l'European Respiratory Society (ERS) et de l'American Thoracic Society (ATS) concernant la classification des pneumonies interstitielles. Les avanc & eacute;es les plus marquantes comprennent l'inclusion des troubles idiopathiques et secondaires dans un cadre de classification unique et adaptable, la distinction entre le sch & eacute;ma morphologique et le diagnostic multidisciplinaire, l'adoption d'une terminologie qui refl & egrave;te plus fid & egrave;lement la biologie et la morphologie, l'identification de sous-groupes cliniquement pertinents et l'& eacute;tablissement d'un niveau de confiance diagnostique tant pour le sch & eacute;ma morphologique que pour le diagnostic multidisciplinaire. Les lecteurs sont encourag & eacute;s & agrave; se familiariser avec ces mises & agrave; jour et & agrave; int & eacute;grer ces avanc & eacute;es afin de contribuer & agrave; am & eacute;liorer les soins aux patients et & agrave; mieux comprendre ces troubles complexes.

BACKGROUND:Sex is an important part of life for many adults, yet sexual function may be impacted by chronic respiratory diseases such as pulmonary fibrosis (PF). This multinational study sought to characterise the impact of PF on sex and sexual function, using mixed quantitative and qualitative methodology. METHODS:We analysed data from a patient registry, a clinical study, an online survey and patient interviews to accomplish our objective and develop a conceptual framework for describing the effects of PF on sex-related quality of life. These cohorts used three distinct questionnaires, University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ), Sheffield Profile for Assessment and Referral to Care (SPARC) questionnaire, and Changes in Sexual Function Questionnaire (CSFQ), to assess sexual dysfunction, respectively. Individual patient interviews were conducted and qualitatively evaluated using thematic analysis. RESULTS:Dyspnoea with sexual activity affected 2054/2759 (74%) of registry patients, associated with male sex, lower forced vital capacity (FVC) % predicted, lower diffusing capacity of the lung for carbon monoxide (D LCO) % predicted and worse cough. Distress due to the effect of PF on their sex life was reported in 52/225 (23%) of the clinical cohort, associated with younger age, male sex, lower D LCO % predicted and worse cough. Sexual dysfunction was common, affecting 56/67 (83%) female and 63/73 (86%) male survey respondents. Qualitative analysis of patient interviews identified several themes, including sex life limitations, changes in interpersonal relationships and quality of life. All patients wanted to discuss sex with trusted healthcare providers. CONCLUSIONS:In this multinational study, patients with PF reported engaging in sex and sexual activities but were adversely impacted by the effect of PF on their sex life, with both physical and psychological limitations. Sexual dysfunction was common, driven by multiple disease domains. Sexual health appears to be an important component of comprehensive patient care.

BACKGROUND. Interstitial lung abnormalities (ILA) on chest CT are receiving growing attention given their association with progression to interstitial lung disease. Radiography's role in ILA detection is not well described. OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance of radiologists and an artificial intelligence (AI) model in detecting ILA on chest radiography using CT as the reference standard. METHODS. This retrospective study included adults who underwent both chest CT and chest radiography as part of health checkup programs at two institutions in Korea between January 2007 and December 2010. Five thoracic radiologists independently assessed the likelihood of ILA on radiography using a 5-point Likert scale (positive, ≥ 4). A previously developed AI model processed radiographs to generate a probability (0-1) of reticular or reticulonodular opacities (positive, ≥ 0.4). CT served as the reference standard for fibrotic and nonfibrotic ILA. Radiologists' diagnostic performance for ILA detection was reported using mean performance metrics and compared with AI performance using generalized estimating equations. Associations of AI-based radiographic ILA, adjusting for age, sex, and smoking status, were assessed with all-cause mortality and respiratory disease-related mortality using Cox proportional hazards and Fine-Gray competing-risk regression models. RESULTS. The analysis included 1168 individuals (median age, 56 years; 786 men, 382 women). Forty-one individuals had ILA on CT (fibrotic, 22; nonfibrotic, 19). For fibrotic ILA, radiologists and AI had AUCs of 0.86 and 0.92 (p = .06), sensitivity of 62.7% and 68.2% (p = .43), specificity of 97.8% and 98.7% (p = .05), and accuracy of 97.2% and 98.1% (p = .04), respectively. For fibrotic or nonfibrotic ILA, radiologists and AI had AUCs of 0.75 and 0.83 (p = .009), sensitivity of 38.5% and 41.5% (p = .48), specificity of 98.0% and 98.8% (p = .05), and accuracy of 95.9% and 96.8% (p = .03), respectively. During a median follow-up of 11.9 years, radiographic ILA was independently associated with respiratory disease-related mortality (adjusted subdistribution HR, 8.72; p < .001) but not overall mortality (adjusted HR, 1.75; p = .17). CONCLUSION. Radiologists and AI achieved suboptimal sensitivity, albeit high specificity, for ILA detection on radiography. CLINICAL IMPACT. Despite association of radiographic ILA with a clinically relevant outcome, the findings do not support radiographic screening for ILA, whether incorporating radiologist or AI interpretation.

RATIONALE:Familial pulmonary fibrosis (FPF), defined as fibrosing interstitial lung disease (ILD) affecting two or more family members, is associated with earlier-onset and a more aggressive disease phenotype. Imaging findings may vary between relatives, complicating diagnosis. While genetic testing exists, it is limited by accessibility and the rarity of monogenic causes. Patient-reported family history may serve as a valuable adjunct prognostic marker. OBJECTIVES:This study aimed to characterize the clinical and radiological features of patients with FPF using a multicenter ILD registry. We compared lung function and transplant-free survival between patients with FPF and sporadic ILD, overall and by radiologic pattern. METHODS:The multicenter Canadian Registry for Pulmonary Fibrosis includes patients with fibrotic ILD. Demographics, forced vital capacity (FVC%), diffusion capacity for carbon monoxide (DLCO%), and death or lung transplant data were collected. Family history was determined via physician or patient documentation. A subset underwent re-evaluation where baseline radiologic features and patterns were described. Statistical comparisons used chi-square tests, Cox proportional hazards, omnibus test and mixed models to assess outcomes. RESULTS:Of 5375 patients, 719 (13%) had FPF. Demographics were similar between FPF and sporadic ILD. When grouping idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis and unclassifiable ILD together, those with FPF were younger (P < .001), more likely female (P < .001), less likely to have smoked (P = .007), and had higher baseline DLCO% (P < .001). Antifibrotics were more often prescribed to FPF patients with fibrotic hypersensitivity pneumonitis, unclassifiable ILD, and systemic autoimmune rheumatic disease-ILD versus their sporadic counterparts. The mean annual rate of FVC% decline was greater in patients with FPF compared to those with sporadic ILD (P = .024). FPF more frequently received referral for transplant (P < .001), but transplant-free survival did not differ between FPF and sporadic disease. In the radiologic cohort (n = 1519) those with FPF had a higher likelihood of radiologic usual interstitial pneumonia than those with sporadic ILD (P = .004). CONCLUSIONS:FPF accounts for a meaningful proportion of ILD cases and exhibits distinct clinical features in certain disease subtypes. Although survival outcomes were similar in this study, earlier onset and accelerated progression highlight the need for refined diagnostic and prognostic approaches to familial disease.

Background: We sought to analyze the effect of a palliative care intervention on quality of life (QoL) in patients with fibrotic interstitial lung disease (fILD). Design: This was a prospective observational study including 14 patients with fILD treated with a bundle of care provided by multidisciplinary specialists in pain and palliative care, a psychologist, physical therapists, and a nutritionist, with all patients initiating 10 mg of morphine sulfate. Measurements at baseline, 30 days, and 90 days included cough, dyspnea, pain, tiredness, nausea, depression, anxiety, sleepiness, appetite, and difficulty sleeping. QoL was recorded using the modified St. George’s Respiratory Questionnaire (SGRQ-1). Change over time in each endpoint was analyzed. Results: Baseline assessment reflected an impaired QoL (median SGRQ-1, 91 points). All symptom scores improved at 90 days, with a statistically significant and clinically meaningful 20-point decrease in the SGRQ-1 ( p = 0.001). Conclusion: Palliative care intervention improves symptom and QoL in fILD.

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:Combined pulmonary fibrosis and emphysema (CPFE) is an important phenotype in patients with fibrotic interstitial lung disease (ILD). RESEARCH QUESTION:What is the prevalence of CPFE? What is the predictive performance of the CPFE index and of physiologic airflow obstruction for CT imaging emphysema extents? Is the extent of emphysema on CT imaging associated with outcomes in patients with fibrotic ILD? STUDY DESIGN AND METHODS:Consecutive patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD who underwent a standardized visual assessment of the baseline high-resolution CT imaging of the chest from a prospective registry were included. CPFE was defined as emphysema extent of ≥ 15% on CT imaging, with sensitivity analyses using different thresholds: ≥ 5%, ≥ 10%, and ≥ 20%. Emphysema subtypes were categorized based on their predominant distribution: centrilobular, paraseptal, or panlobular. The CPFE index was derived using measurements of spirometry and diffusion capacity of the lungs for CO2. RESULTS:The prevalence of CPFE at baseline was 20% for IPF (92/455) and 7% in non-IPF fibrotic ILD (84/1121). Both FEV1 to FVC ratio less than the lower limit of normal and < 0.70 showed poor sensitivity (IPF, 11.1%-18.9%; non-IPF fibrotic ILD, 13.1%-23.7%) for detecting emphysema on CT imaging, although high specificity (IPF, 96.2%-98.8%; non-IPF fibrotic ILD, 92.8%-95.8%). The CPFE index was correlated moderately with extent of emphysema on CT imaging in both IPF (r = 0.48) and non-IPF fibrotic ILD (r = 0.41), but with poor agreement and wide limits of agreement on Bland-Altman analysis. Extent of emphysema on CT imaging of ≥ 20% was associated consistently with differences in lung function trajectories and worse transplant-free survival in IPF and non-IPF fibrotic ILD. No significant relationships were noted between emphysema subtypes and health outcomes. INTERPRETATION:Our results show that coexisting emphysema is important in both IPF and non-IPF fibrotic ILD, with extent of emphysema on CT imaging of ≥ 20% being associated with worse health outcomes. Both physiologic and radiologic assessments are needed to identify coexistent emphysema in patients with fibrotic ILD.

RATIONALE:Fibrotic interstitial lung diseases (ILDs) cause loss of forced vital capacity (FVC) and increased risk of death over time. Most clinical trials aim to slow FVC decline and reduce mortality. However, the association of lower FVC with higher mortality will bias simple estimates of differences in FVC progression between groups. Therefore, both the time-dependent decline in FVC and increase in mortality should be jointly modeled. METHODS:We developed a Bayesian, joint mixed-effects disease progression model (DPM), using minimally informative prior distributions, for FVC trajectory and the hazard for ILD-related mortality over time. This model minimizes bias due to mortality in estimating differences in the rate of FVC decline and is suitable for use when characterizing populations or in estimating a treatment effect in a clinical trial. The DPM was applied to individual patient data from prospective cohort studies of fibrotic ILD. MEASUREMENTS AND MAIN RESULTS:The DPM yields a higher estimated rate of FVC decline (6.0% vs 4.7%/year) and a more precise fit than a linear mixed model of FVC alone, and replicates the nonlinear pattern in the observed data. By modeling the full FVC trajectory rather than only the change from baseline at a given time point, the DPM increases the information from each patient and reduces both the time to information and the effect of variability in baseline FVC measurements on the estimation of treatment effects. CONCLUSIONS:The joint DPM provides an integrated approach to minimizing bias in the estimation of treatment effects in clinical trials in fibrotic ILDs.

Many patients with fibrotic interstitial lung disease (ILD) also have comorbid diabetes, for which they take metformin. Metformin use has been shown to have lung fibrosis attenuation potential based on laboratory research but studies in human populations have yielded inconsistent results. To investigate this, 2,226 patients with fibrotic ILD from the large, prospective Canadian Registry for Pulmonary Fibrosis were analyzed for lung function at baseline and up to 2-year follow up. Joint modeling was used to assess the association of baseline metformin use with longitudinal lung forced vital capacity change and survival (death or lung transplant), adjusting for age, sex, smoking pack-years, baseline lung function, medication use. Results showed that baseline metformin use was not significantly associated with attenuation of forced vital capacity decline in the overall interstitial lung disease cohort, or in the subgroups based on presence of a diagnosis of idiopathic pulmonary fibrosis or diabetes. Kaplan–Meier and Cox analyses suggested a trend toward increased mortality or transplant risk associated with metformin use in all cohorts, although this was not statistically significant after adjustment for other variables. In our study, metformin did not significantly alter lung function decline in fibrotic ILD despite laboratory evidence of antifibrotic properties.

RATIONALE:Common and rare variants that are associated with the risk of developing idiopathic pulmonary fibrosis (IPF) have been identified predominantly in European ancestry populations. OBJECTIVES:To better understand the genetic variants that contribute to IPF in individuals with Asian ancestry, we conducted a genome-wide association study of IPF in East Asian populations. METHODS:We included 1026 patients with IPF and compared them to 1723 unaffected controls of Japanese and Korean ancestry. Genome-wide association analysis was conducted in the Japanese and Korean ancestry cohorts separately and combined using meta-analysis. Restricted maximum likelihood was used to estimate the SNP-based heritability and local ancestry of chromosome 11 was inferred for each subject. MEASUREMENTS AND MAIN RESULTS:We identified loci on chromosomes 4 (FAM13A; rs7690839), 5 (TERT; rs7734992), 6 (DSP; rs2076295), and 11 (MUC5B; rs35705950) that were significantly associated with risk of IPF. Importantly, the sentinel variants in each of these loci are the same as, or in strong linkage disequilibrium with, the risk variants that have been observed in studies of European ancestry populations. In aggregate, common variants (not including the MUC5B promoter variant) account for approximately 25% of the risk of developing IPF in these East Asian ancestry cohorts. Moreover, local ancestry analysis indicates that the presence of MUC5B promoter variant in the East Asian population is not a result of admixture with European ancestry populations. CONCLUSIONS:We conclude that the IPF risk loci in East Asian populations are shared with those of European ancestry populations, although their risk allele frequencies and effect sizes differ. These findings indicate shared genetic risk factors of IPF across ancestries.

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.

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.

Long-term smokers with persistent dyspnoea and exercise intolerance, who are at risk for COPD, require careful clinical assessment. However, many such individuals have only minor abnormalities on spirometry, and it is not known if various additional tests of small airways dysfunction (SAD) or pulmonary microvascular deficits, offer added clinical value. In this study we wished to determine which of the available resting pulmonary function tests (e.g. airway mechanics and lung diffusing capacity for carbon monoxide, DLCO) best uncover the physiological underpinnings of these troublesome respiratory symptoms. This tri-centre, prospective study enrolled 90 volunteers: 33 non-smoker controls, 57 symptomatic smokers, 38 of whom had Global Initiative for Obstructive Lung Disease Grade 1 COPD). Participants completed impulse oscillometry (IOS), spirometry, body plethysmography, DLCO, single and multiple breath nitrogen washout and an incremental cycle cardiopulmonary exercise test. Smokers had more diverse physiological abnormalities, greater dyspnoea and exercise intolerance than healthy controls. Stepwise multilinear regression revealed that DLCO was the only independent predictor of dyspnoea burden (ratio of peak dyspnoea score to peak oxygen uptake (V̇O2peak)), lower V̇O2peak, higher ventilatory equivalent for carbon dioxide (V̇E/V̇CO2 nadir) and dynamic inspiratory mechanical constraints (higher tidal volume to inspiratory capacity ratio), after accounting for age, sex, height, and smoking history. In symptomatic smokers, reduced DLCO, contributed more to the variance in exertional dyspnoea and exercise intolerance than all airway mechanical measurements. This attests to the added value of DLCO for clinicians assessing the nature and extent of smoking-related lung injury in individuals with only minor airway obstruction.

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.

Introduction The role of gastroesophageal reflux disease (GERD) and proton pump inhibitors (PPI) in fibrotic interstitial lung disease (fILD) remains unclear. We evaluated the association of GERD and PPI use with cough severity and major pulmonary outcomes in patients with fibrotic ILD. Methods This retrospective analysis of a prospective cohort study consisted of patients with fibrotic ILD enrolled in the CAnadian REgistry for Pulmonary Fibrosis. Patients were categorized by the presence of GERD and PPI use based on patient self-report and verified by review of the medical record. We evaluated the unadjusted and adjusted association of GERD and PPI use with cough severity visual analog scale (VAS), change in lung function, and mortality. Results 2,238 patients with fILD were included, of whom 731 had idiopathic pulmonary fibrosis. GERD was present in 777 patients (35%), with 494 (64%) of these reporting PPI use. GERD was associated with worse baseline cough severity VAS [36 mm (21-59) vs 30 mm (17-55), p=0.007), with no difference between PPI users and non-users (p=0.89). There was no consistent association of GERD or PPI use with change in lung function or transplant-free survival, with PPI use tending to be associated with worse outcomes only upon adjustment for age, sex, body mass index, and smoking pack-years (HR 1.31, 95%CI 1.02-1.67, p=0.03). Conclusions GERD is associated with worse cough severity in fILD, but PPI use is not associated with less cough. Neither GERD nor PPI use was consistently associated with change in lung function or transplant-free survival.