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Background: Progressive pulmonary fibrosis (PFF) is of substantial interest for novel pharmacotherapy discovery, but little is known about clinical trial eligibility criteria. We evaluated eligibility criteria of PPF randomized controlled trials (RCTs), their representativeness in registry patients, and forced vital capacity (FVC) changes and mortality according to trial eligibility., Methods: A systematic search was used to identify completed and in-progress phase II and III PPF RCTs. Common clinical trial eligibility criteria used in ≥60% of previous PPF RCTs were identified. The most common criteria for PPF used in RCTs ("trial-PPF criteria") and the clinical practice guideline definition of PPF ("guideline-PPF criteria") were both applied to patients enrolled in a prospective multicenter Canadian registry. Common trial eligibility criteria were tested for their frequency and association with health outcomes in registry patients who met trial-PPF and guideline-PPF criteria., Results: Ten different definitions of PPF were used in 16 RCTs. At the time of meeting PPF definitions, 50% of 864 patients with trial-PPF and 44% of 408 patients with guideline-PPF met the common trial eligibility criteria. For both definitions, trial-eligible patients had more rapid 1-year FVC decline but better transplant-free survival than trial-ineligible patients. Patients with unclassifiable interstitial lung disease (ILD) had higher proportion of trial exclusion compared to those with connective tissue disease-associated ILD and fibrotic hypersensitivity pneumonitis. Annual FVC decline (trial-PPF: -67 to -21 mL; guideline-PPF: -116 to -41 mL) and 1-year transplant-free survival (trial-PPF: 90.5 to 97.5%; guideline-PPF: 87 to 96.2%) varied in trial-eligible patients across ILD subtypes., Conclusions: Existing RCTs use a variety of definitions for PPF with eligibility criteria that have limited representativeness. FVC decline and transplant-free survival vary according to trial eligibility and ILD subtypes., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Respiratory diseases exhibit diverse patterns in prevalence, clinical presentations, and outcomes between men and women. Historically, certain conditions were more prevalent in men, but trends have shifted, highlighting the need to understand sex disparities in respiratory health. Social, environmental, and healthcare changes have reshaped the landscape of respiratory diseases, complicating diagnosis and treatment. Moreover, the underrepresentation of women in clinical trials has limited our understanding of their specific needs. In this review, we explore the sex differences in the prevalence, clinical characteristics, and presentation of respiratory diseases, emphasizing the importance of tailored approaches to diagnosis and management. By recognizing and addressing these disparities, we can advance toward more equitable and effective respiratory healthcare for all individuals., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Rationale: Cough is a key symptom in patients with fibrotic interstitial lung disease (ILD). Objectives: This study evaluated the prevalence, longitudinal change, associations, and prognostic significance of cough severity in patients with fibrotic ILD. Methods: We included consecutive patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD who completed the 100-mm Cough Severity Visual Analog Scale from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. Baseline cough severity and associations with patient demographics and clinical factors were determined. Relationships between baseline cough severity and health outcomes were evaluated. Measurements and Main Results: Patients with IPF ( n  = 1,061) had higher median baseline cough severity than those with non-IPF fibrotic ILD ( n  = 2,825) (24 vs. 20 mm; P  < 0.001), with worse cough associated with gastroesophageal reflux disease for both cohorts. Worse cough severity was independently associated with worse health-related quality of life at baseline, larger annualized decline in Dl CO , development of disease progression, and reduced transplant-free survival in both IPF and non-IPF fibrotic ILD cohorts. The IPF cohort (2.2 mm; 95% confidence interval, 1.6-2.9 mm) had larger annualized increments in cough severity than the non-IPF fibrotic ILD cohort (1.1 mm; 95% confidence interval, 0.8-1.4 mm; P  = 0.004). There was no difference in worsening cough over time comparing those receiving and not receiving ILD-targeted therapy or with and without lung function decline. Conclusions: Cough is common in patients with IPF and non-IPF fibrotic ILD, with increasing cough severity over time irrespective of ILD-targeted therapy. Patient-reported cough severity has prognostic implications on health-related quality of life, disease progression, and survival in fibrotic ILD.

Rationale: A visual analog scale (VAS) is a simple and easily administered tool for measuring the impact of disease; however, little is known about the use of a dyspnea VAS in interstitial lung disease (ILD). Objectives: To validate the use of a dyspnea VAS in a large and heterogeneous cohort of patients with fibrotic ILD, including its minimal clinically important difference (MCID), responsiveness to change, and prognostic significance. Methods: Patients with fibrotic ILD were identified from a large prospective registry. The validity of a 100-mm dyspnea VAS was assessed by testing its correlation in change score with other measures of ILD severity, including the University of California San Diego Shortness of Breath Questionnaire, the King's Brief Interstitial Lung Disease quality of life questionnaire Breathlessness and Activities Domain, the European Quality of Life VAS, forced vital capacity, and diffusing capacity of the lung for carbon monoxide. The responsiveness of the dyspnea VAS was qualitatively confirmed on the basis of there being an observable difference in the change in dyspnea VAS across tertiles of change in anchor variables. The MCID in dyspnea VAS was calculated using both anchor (linear regression) and distribution (one-half standard deviation) approaches, with anchors including the above variables that had a correlation with dyspnea VAS (| r | ≥ 0.30). The association of dyspnea VAS with time to death or transplant was determined. Results: The cohort included 826 patients with fibrotic ILD, including 127 patients with follow-up measurements at 6 months. The mean baseline dyspnea VAS was 53 ± 24 mm. Dyspnea VAS change scores were moderately correlated with the University of California San Diego Shortness of Breath Questionnaire (| r | = 0.55) and the King's Brief Interstitial Lung Disease quality of life questionnaire Breathlessness and Activities Domain (| r | = 0.44) and weakly correlated with the European Quality of Life VAS (| r | = 0.19), forced vital capacity percent predicted (| r | = 0.21), and diffusing capacity of the lung for carbon monoxide percent predicted (| r | = 0.05). The MCID was 2.7 to 4.5 using the more reliable anchor-based methods and 12.0 based on distribution-based methods. Dyspnea VAS was associated with time to death or transplant in unadjusted models and after adjustment for age and sex (hazard ratios, 1.16 and 1.15, respectively; P  < 0.05 for both). Conclusions: This study provides support for the use of the dyspnea VAS in patients with fibrotic ILD, with an estimated anchor-based MCID of 5 mm.

Background and Objective: Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non-negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis., Methods: Linear mixed models and Cox proportional hazards regression models were used to compare decline in forced vital capacity (FVC)%, diffusion capacity of the lung (DLCO%) and risk of death or lung transplantation between SLB and non-SLB patients. Adjustments were made for baseline age, sex, smoking history, antifibrotic use, and lung function. A similar analysis compared lung function changes 12 months pre- and post-SLB., Results: A total of 81 SLB patients and 468 non-SLB patients were included. In the SLB group, the post-biopsy annual FVC% decline was 2.0% (±0.8) in unadjusted, and 2.1% (±0.8) in adjusted models. There was no difference in FVC% decline, DLCO% decline, or time to death or lung transplantation between the two groups, in adjusted or unadjusted models (all p-values >0.07). In the pre-post SLB group, no differences were identified in FVC% decline in unadjusted or adjusted models (p = 0.07 for both)., Conclusion: No association between SLB and lung function decline or risk of death or lung transplantation was identified in this multi-centre study of patients with IPF., (© 2024 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: Patients with fibrotic hypersensitivity pneumonitis (fHP) are frequently treated with immunosuppression to slow lung function decline; however, the impact of this treatment has not been studied across different types of antigen exposure., Research Question: In patients with fHP, do disease outcomes and response to treatment vary by antigen type?, Study Design and Methods: A multicenter interstitial lung disease database (Canadian Registry for Pulmonary Fibrosis) was used to identify patients with fHP. The causative antigen was categorized as avian, mold, unknown, or other. Treatment was defined as mycophenolate ≥ 1,000 mg/d or azathioprine ≥ 75 mg/d for ≥ 30 days. Statistical analysis included t tests, χ 2 tests, and one-way analysis of variance. Unadjusted and adjusted competing risks and Cox proportional hazards models were used to assess survival., Results: A total of 344 patients were identified with the following causative antigens: avian (n = 93; 27%), mold (n = 88; 26%), other (n = 15; 4%), and unknown (n = 148; 43%). Patient characteristics and lung function were similar among antigen groups with a mean FVC % predicted of 75 ± 20. The percent of patients treated with immunosuppression was similar between antigens with 58% of patients treated. There was no change in lung function or symptom scores with the initiation of immunosuppression in the full cohort. Immunosuppression was not associated with a change in survival for patients with avian or mold antigen (avian: hazard ratio, 0.41; 95% CI, 0.11-1.59; P = .20; mold: hazard ratio, 1.13; 95% CI, 0.26-4.97; P = .88). For patients with unknown causative antigen, survival was worse when treated with immunosuppression (hazard ratio, 2.65; 95% CI, 1.01-6.92; P = .047)., Interpretation: Response to immunosuppression varies by antigen type in patients with fHP. Additional studies are needed to test the role of immunosuppression in fHP, and particularly in those with an unknown antigen., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. W. W. reports personal fees from Boehringer Ingelheim and Astra Zeneca, outside the submitted work. V. M. reports personal fees from Boehringer Ingelheim Canada, Hoffman-La Roche Ltd, and Astra Zeneca; and reports grants from the University of Saskatchewan, Royal University Hospital Foundation, Boehringer Ingelheim, Astra Zeneca, and Hoffman-La Roche. D.-C. M. reports consultancy and speaking fees from Boehringer Ingelheim. B. Z. reports speaking fees from Boehringer Ingelheim and Abbvie. D. A. is supported by the Fonds de Recherche du Quebec en Santé, reports personal fees and grants from Boehringer Ingelheim, reports personal fees from Hoffmann-La Roche, and reports grants from the Canadian Institute for Health Research. K. A. J. reports grants from Boehringer Ingelheim, Pulmonary Fibrosis Society of Calgary, and University of Calgary School of Medicine; and reports personal fees from Boehringer Ingelheim, Roche, Three Lakes Foundation, Pliant Therapeutics, Theravance, and Blade Therapeutics. M. K. reports grants from the Canadian Institute for Health Research, Roche, Boehringer Ingelheim, Pieris, and Prometic; and reports personal fees from Boehringer Ingelheim, Roche, European Respiratory Journal, Belerophon, United Therapeutics, Nitto Denko, MitoImmune, Pieris, Abbvie, DevPro Biopharma, Horizon, Algernon, and CSL Behring. H. M. reports grants from Boehringer Ingelheim and Gilead. J. M. reports personal fees from Boehringer Ingelheim and Roche. C. J. R. reports grants from Boehringer Ingelheim; and reports personal fees from Astra Zeneca, Boehringer Ingelheim, Roche, Pliant Therapeutics, Cipla, and Veracyte. None declared (M. L. M., G. F., J. H. F., N. K., B. M., E. F.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Fibrotic interstitial lung disease (ILD) is frequently associated with abnormal oxygenation; however, little is known about the accuracy of oxygen saturation by pulse oximetry (SpO 2 ) compared with arterial blood gas (ABG) saturation (SaO 2 ), the factors that influence the partial pressure of carbon dioxide (PaCO 2 ) and the impact of PaCO 2 on outcomes in patients with fibrotic ILD., Study Design and Methods: Patients with fibrotic ILD enrolled in a large prospective registry with a room air ABG were included. Prespecified analyses included testing the correlation between SaO 2 and SpO 2 , the difference between SaO 2 and SpO 2 , the association of baseline characteristics with both the difference between SaO 2 and SpO 2 and the PaCO 2 , the association of baseline characteristics with acid-base category, and the association of PaCO 2 and acid-base category with time to death or transplant., Results: A total of 532 patients with fibrotic ILD were included. Mean resting SaO 2 was 92±4% and SpO 2 was 95±3%. Mean PaCO 2 was 38±6 mmHg, with 135 patients having PaCO 2 <35 mmHg and 62 having PaCO 2 >45 mmHg. Correlation between SaO 2 and SpO 2 was mild to moderate (r=0.39), with SpO 2 on average 3.0% higher than SaO 2 . No baseline characteristics were associated with the difference in SaO 2 and SpO 2 . Variables associated with either elevated or abnormal (elevated or low) PaCO 2 included higher smoking pack-years and lower baseline forced vital capacity (FVC). Lower baseline lung function was associated with an increased risk of chronic respiratory acidosis. PaCO 2 and acid-base status were not associated with time to death or transplant., Interpretation: SaO 2 and SpO 2 are weakly-to-moderately correlated in fibrotic ILD, with limited ability to accurately predict this difference. Abnormal PaCO 2 was associated with baseline FVC but was not associated with outcomes., Competing Interests: Competing interests: MAD reports no conflicts of interest relevant to this manuscript. KD reports no conflicts of interest relevant to this manuscript. DA reports grants and personal fees from Boehringer Ingelheim, grants from Canadian Institute for Health Research and from Fonds de Recherche du Quebec en Santé. CD reports no conflicts of interest relevant to this manuscript. JHF reports personal fees from AstraZeneca and Boehringer Ingelheim. KJ reports grants from Boehringer Ingelheim, Pulmonary Fibrosis Society of Calgary, University of Calgary School of Medicine; personal fees from Boehringer Ingelheim, Roche, Three Lakes Foundation, Pliant Therapeutics, Theravance, Blade Therapeutics. MK reports grants from Canadian Institute for Health Research, Roche, Boehringer Ingelheim, Pieris, Prometic; personal fees from Boehringer Ingelheim, Roche, European Respiratory Journal, Belerophon, United Therapeutics, Nitto Denko, MitoImmune, Pieris, AbbVie, DevPro Biopharma, Horizon, Algernon, CSL Behring. SDL reports consulting/personal fees and moderator honoraria from Boehringer-Ingelheim, honoraria from Hoffman-La Roche Ltd, grants from AstraZeneca and the University of Saskatchewan. HM reports grants from Boehringer Ingelheim and Gilead. VM reports grants from Boehringer Ingelheim, AstraZeneca, and Roche; personal fees from Boehringer Ingelheim and Roche. BM reports no conflicts of interest relevant to this manuscript. JM reports personal fees from Boehringer Ingelheim and Roche. D-CM reports personal fees from Boehringer Ingelheim. CJR reports grants from Boehringer Ingelheim; personal fees from AstraZeneca, Boehringer Ingelheim, Roche, Pliant Therapeutics, Cipla, Veracyte., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Interstitial pneumonia with autoimmune features (IPAF) has features of connective tissue disease-associated interstitial lung disease (CTD-ILD), but without meeting criteria for a specific CTD. We compared baseline characteristics, survival, and response to treatment of IPAF to both CTD-ILD and unclassifiable ILD., Methods: Measurements were extracted from a prospective registry. Baseline features and survival were compared in IPAF against both CTD-ILD and unclassifiable ILD. Linear trajectory of lung function decline (%-predicted forced vital capacity [FVC%] and diffusion capacity of the lung for carbon monoxide [DLCO%]) before and after initiation of mycophenolate or azathioprine were compared in IPAF against both CTD-ILD and unclassifiable ILD using linear mixed models., Results: Compared to CTD-ILD (n = 1240), patients with IPAF (n = 128) were older, more frequently male, and had greater smoking history. Compared to unclassifiable ILD (n = 665), patients with IPAF were younger, more frequently female, and had worse baseline lung function. IPAF had higher mortality compared to CTD-ILD and similar risk of mortality compared to unclassifiable ILD. Mycophenolate initiation was associated with stabilization of FVC% and DLCO% in all ILD subtypes except for FVC% in patients with IPAF, and azathioprine initiation with stabilization of FVC% and DLCO% in all ILD subtypes except for FVC% decline in IPAF and DLCO% decline in CTD-ILD., Conclusion: Patients with IPAF had worse survival compared to those with CTD-ILD and similar mortality to unclassifiable ILD, with treatment being associated with stabilization in lung function in all three ILDs. It is uncertain whether IPAF should be considered a distinct ILD diagnostic subgroup., Competing Interests: Declaration of competing interest CJR, NK, KAJ, DA, HM, JF, MK, NH, SV report personal fees from Boehringer Ingelheim. Conflict of interest: SV reports no conflicts of interest relevant to this manuscript. Conflict of interest: JA reports no conflicts of interest relevant to this manuscript. Conflict of interest: BZ reports no conflicts of interest relevant to this manuscript. Conflict of interest: K. Donohoe reports no conflicts of interest relevant to this manuscript. Conflict of interest: N. Hambly reports grants from Roche and Janssen; personal fees from Roche, Boehringer Ingelheim, GSK and Janssen. Conflict of interest: K.A. Johannson reports grants from Three Lakes and University Hospital Foundation. K.J. reports consulting fees from Boehringer-Ingelheim, Hoffman-La Roche Ltd, Pliant Therapeutics, Three Lakes, Thyron and Brainomix. Conflict of interest: D. Assayag reports no conflicts of interest relevant to this manuscript. Conflict of interest: J. Fisher reports no conflicts of interest relevant to this manuscript. Conflict of interest: V. Marcoux reports personal fees from Boehringer Ingelheim Canada and Hoffman-La Roche Ltd and Astra Zeneca, grants from the University of Saskatchewan, Boehringer Ingelheim, Astra Zeneca and Hoffman-La Roche. VM reports consulting fees from Boehringer Ingelheim Canada and Hoffman-La Roche Ltd. Conflict of interest: H. Manganas reports grants from Boehringer Ingelheim Canada, Hoffmann La Roche, Galapagos, BMS. Conflict of interest: N. Khalil reports no conflicts of interest relevant to this manuscript. Conflict of interest: M. Kolb reports consulting fees from Boehringer Ingelheim, Roche, Horizon, Cipla Abbvie, Bellerophon, Algernon, CSL Behring, United Therapeutics, LabCorp, Structure Therapeutics and Astra Zeneca. M. Kolb reports grants from Boehringer Ingelheim, United Therapeutics and Structure Therapeutics. M. Kolb reports payment for expert testimony from Roche. Conflict of interest: C.J. Ryerson reports grants from Boehringer Ingelheim; consulting fees from Boehringer Ingelheim, Trevi Therapeutics, Pliant Therapeutics, Astrazeneca and Veracyte., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rationale: Hypoxemia in fibrotic interstitial lung disease (ILD) indicates disease progression and is of prognostic significance. The onset of hypoxemia signifies disease progression and predicts mortality in fibrotic ILD. Accurately predicting new-onset exertional and resting hypoxemia prompts appropriate patient discussion and timely consideration of home oxygen. Objectives: We derived and externally validated a risk prediction tool for both new-onset exertional and new-onset resting hypoxemia. Methods: This study used ILD registries from Canada for the derivation cohort and from Australia and the United States for the validation cohort. New-onset exertional and resting hypoxemia were defined as nadir oxyhemoglobin saturation < 88% during 6-minute-walk tests, resting oxyhemoglobin saturation < 88%, or the initiation of ambulatory or continuous oxygen. Candidate predictors included patient demographics, ILD subtypes, and pulmonary function. Time-varying Cox regression was used to identify the top-performing prediction model according to Akaike information criterion and clinical usability. Model performance was assessed using Harrell's C-index and goodness-of-fit (GoF) likelihood ratio test. A categorized risk prediction tool was developed. Results: The best-performing prediction model for both new-onset exertional and new-onset resting hypoxemia included age, body mass index, a diagnosis of idiopathic pulmonary fibrosis, and percent predicted forced vital capacity and diffusing capacity of carbon monoxide. The risk prediction tool exhibited good performance for exertional hypoxemia (C-index, 0.70; GoF, P  = 0.85) and resting hypoxemia (C-index, 0.77; GoF, P  = 0.27) in the derivation cohort, with similar performance in the validation cohort except calibration for resting hypoxemia (GoF, P  = 0.001). Conclusions: This clinically applicable risk prediction tool predicted new-onset exertional and resting hypoxemia at 6 months in the derivation cohort and a diverse validation cohort. Suboptimal GoF in the validation cohort likely reflected overestimation of hypoxemia risk and indicated that the model is not flawed because of underestimation of hypoxemia.

Rationale: Transbronchial cryobiopsy (TBCB) for the diagnosis of interstitial lung disease (ILD) has shown promising results, but prospective studies with matched surgical lung biopsy (SLB) have yielded conflicting results. Objectives: We aimed to assess within- and between-center diagnostic agreement between TBCB and SLB at both the histopathologic and multidisciplinary discussion (MDD) levels in patients with diffuse ILD. Methods: In a multicenter prospective study, we performed matched TBCB and SLB in patients referred for SLB. After a blinded review by three pulmonary pathologists, all cases were reviewed by three independent ILD teams in an MDD. MDD was performed first with TBCB, then with SLB in a second session. Within-center and between-center diagnostic agreement was evaluated using percentages and correlation coefficients. Measurements and Main Results: Twenty patients were recruited and underwent contemporaneous TBCB and SLB. Within-center diagnostic agreement between TBCB-MDD and SLB-MDD was reached in 37 of the 60 (61.7%) paired observations, resulting in a Cohen's κ value of 0.46 (95% confidence interval [CI], 0.29-0.63). Diagnostic agreement increased among high-confidence or definitive diagnoses on TBCB-MDD (21 of 29 [72.4%]), but not significantly, and was more likely among cases with SLB-MDD diagnoses of idiopathic pulmonary fibrosis than fibrotic hypersensitivity pneumonitis (13 of 16 [81.2%] vs. 16 of 31 [51.6%]; P  = 0.047). Between-center agreement for cases was markedly higher for SLB-MDD (κ = 0.71 [95% CI, 0.52-0.89]) than TBCB-MDD (κ = 0.29 [95% CI, 0.09-0.49]). Conclusions: This study demonstrated moderate TBCB-MDD and SLB-MDD diagnostic agreement for ILD, while between-center agreement was fair for TBCB-MDD and substantial for SLB-MDD. Clinical trial registered with www.clinicaltrials.gov (NCT02235779).

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is challenging to manage, with a paucity of robust data to guide treatment. Our aim was to characterize the pharmacologic treatment of RA-ILD utilizing a retrospective design in a national multi-center prospective cohort, and to identify associations between treatment and change in lung function and survival., Methods: Patients with RA-ILD and a radiological pattern of non-specific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) were included. Unadjusted and adjusted linear mixed models and Cox proportional hazards models were used to compare lung function change and risk of death or lung transplant by radiologic patterns and treatment., Results: Of 161 patients with RA-ILD, UIP pattern was more common than NSIP (55.9% vs. 44.1%). Only 44/161 (27%) patients were treated over median follow-up of 4 years with medication choice appearing unrelated to patient-specific variables. Decline in forced vital capacity (FVC) was not associated with treatment. Patients with NSIP had lower risk of death or transplant, compared to UIP (P=0.0042). In patients with NSIP, there was no difference in time to death or transplant comparing treated to untreated in adjusted models [hazard ratio (HR) =0.73; 95% confidence interval (CI): 0.15-3.62; P=0.70]. Similarly, in patients with UIP, there was no difference in time to death or lung transplant between treated and untreated in adjusted models (HR =1.06; 95% CI: 0.49-2.28; P=0.89)., Conclusions: Treatment of RA-ILD is heterogeneous, with most patients in this cohort not receiving treatment. Patients with UIP had worse outcomes compared to NSIP, similar to other cohorts. Randomized clinical trials are needed to inform pharmacologic therapy in this patient population., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1820/coif). All authors report that Canadian Registry for Pulmonary Fibrosis is sponsored by Boehringer Ingelheim Canada but it has had no influence on this study design/manuscript. VM reports personal fees from Boehringer Ingelheim Canada and Hoffman-La Roche Ltd., and Astra Zeneca, grants from the University of Saskatchewan, Royal University Hospital Foundation, Boehringer Ingelheim, Astra Zeneca and Hoffman-La Roche. SL reports consulting fees and moderator honoraria from Boehringer-Ingelheim and a grant from the University of Saskatchewan. SL has served on prior advisory boards of Boehringer-Ingelheim. DA reports consulting fees from Boehringer-Ingelheim and Hoffman-La Roche, payments for a lecture from Boehringer-Ingelheim, and research grants from Boehringer Ingelheim. JHF reports grants from the Canadian Pulmonary Fibrosis Foundation and the University of Toronto, and personal fees from Boehringer-Ingelheim and AstraZeneca, outside the submitted work. JHF serves as an unpaid medical advisory board member of Canadian Pulmonary Fibrosis Foundation. SS reports advisory board participation and personal fees from Boehringer-Ingelheim, Hoffman-La Roche, and AstraZeneca. JM reports personal fees from Boehringer-Ingelheim and Hoffman-La Roche. HM reports research grants from Boehringer-Ingelheim, Galapagos, BMS and Hoffman-La Roche, personal fees from Boehringer-Ingelheim, and participates on an advisory board for Boehringer Ingelheim. CDF reports educational grants and research grants from Boehringer-Ingelheim, Roche and the Canadian Pulmonary Fibrosis Foundation; personal fees from Roche and Boehringer Ingelheim; Chair of the Board for the Canadian Pulmonary Fibrosis Foundation. NH reports research grants from Boehringer-Ingelheim and Janssen, and personal fees from Boehringer-Ingelheim, Janssen, and Hoffman-La Roche. MK serves as an unpaid editorial board member of Journal of Thoracic Disease. MK reports grants from Boehringer-Ingelheim, Hoffman-La Roche and Pieris, personal fees from Boehringer Ingelheim, Hoffman-La Roche, Horizon, Cipla, Abbvie, Bellerophon, Algernon, CSL Behring, United Therapeutics Novartis and LabCorp, participation on the advisory board of United Therapeutics Novartis and LabCorp, and allowance for serving as Chief Editor of the European Respiratory Journal. MS reports honoraria for attending symposia from Boehringer-Ingelheim. AWW reports speaker’s honoraria from Boehringer-Ingelheim and AstraZeneca. PGW reports payment for presentation from Vertex. PGW is a member of the Cystic Fibrosis Foundation Drug Safety Monitoring Board. CJR reports personal fees from Boehringer-Ingelheim, Hoffman-La Roche, Veracyte, AstraZeneca, Pliant Therapeutics, Cipla Ltd., and Ensho Health. KAJ reports grants from University Hospital Foundation, Three Lakes Foundation and University oof Calgary CSM, and personal fees from Boehringer-Ingelheim, Hoffman-La Roche, Pliant Therapeutics and Three Lakes Foundation. KAJ is a member of the board for PFOX Trial. The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria., Methods: Common eligibility criteria used in >60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries. Additional pre-specified criteria of 6-min walk distance (6MWD) and different measures of preceding disease progression were also evaluated. Joint longitudinal-survival modelling was used to compare FVC decline according to eligibility for individual and composite criteria., Results: Out of 990 patients with IPF, 527 (53%) met all common RCT eligibility criteria at the first clinic visit, including 343 with definite IPF and 184 with radiological probable usual interstitial pneumonia pattern without histological confirmation ( i.e. provisional IPF). The percentages of eligible patients for landmark RCTs of nintedanib and pirfenidone were 19-50%. Adding 6MWD ≥150 m and different measures of preceding disease progression to the composite common criteria reduced the percentages of patients meeting eligibility to 52% (n=516) and 4-18% (n=12-61), respectively. Patients meeting the composite common criteria had less-rapid 1-year FVC decline than those who did not (-90 versus -103 mL, p=0.01). Definite IPF generally had more-rapid 1-year FVC decline compared to provisional IPF., Conclusions: Eligibility criteria of previous IPF RCTs have limited generalisability to clinical IPF populations, with FVC decline differing between eligible and ineligible populations., Competing Interests: Conflict of interest: Y.H. Khor reports fellowship support from NHMRC Investigator Grant, and support for the CARE-PF registry (with no influence on this study) from Boehringer Ingelheim, during the conduct of the study. K.A. Johannson reports personal fees, non-financial support and other from Boehringer Ingelheim, personal fees from Hoffman-La Roche Ltd, Pliant Therapeutics and Thyron, grants from University Hospital Foundation, Pulmonary Fibrosis Society of Calgary and University of Calgary Cumming School of Medicine, and personal fees and non-financial support from Three Lakes Foundation, outside the submitted work. V. Marcoux reports grants from Boehringer Ingelheim, during the conduct of the study; grants from University of British Columbia and Boehringer Ingelheim, outside the submitted work. J.H. Fisher reports grants from Boehringer Ingelheim, during the conduct of the study; grants from Canadian Pulmonary Fibrosis Foundation and University of Toronto, and personal fees from Boehringer Ingelheim and AstraZeneca, outside the submitted work. D. Assayag reports grants from Boehringer Ingelheim Canada, and lecture honoraria from Boehringer Ingelheim and Hoffman La Roche, outside the submitted work. H. Manganas reports support for the present manuscript from University of British Columbia; grants from Boehringer Ingelheim Canada, Hoffmann La Roche, Galapagos and BMS, honoraria for educational events from Boehringer Ingelheim Canada, and advisory board membership for Boehringer Ingelheim Canada, outside the submitted work. M. Kolb reports grants from Boehringer Ingelheim, Pieris and Roche, consulting fees from Boehringer Ingelheim, Roche, Horizon, Cipla, Abbvie, Bellerophon, Algernon, CSL Behring, United Therapeutics and LabCorp, lecture honoraria from Roche, Novartis and Boehringer Ingelheim, payment for expert testimony from Roche, advisory board participation with United Therapeutics and LabCorp, and reports an editorial allowance from ERJ, outside the submitted work. C.J. Ryerson reports grants from Boehringer Ingelheim, during the conduct of the study; grants and personal fees from Boehringer Ingelheim and Hoffmann-La Roche, and personal fees from Veracyte, Pliant Therapeutics, AstraZeneca and Cipla Ltd, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Biological sex, gender, and race are important considerations in patients with interstitial lung diseases (ILDs)., Research Question: Does a patient's sex assigned at birth, and race, influence ILD treatment initiation?, Study Design and Methods: Patients with ILD from three longitudinal prospective registries were compared in this observational study. ILD-related medications included antifibrotics and immunomodulating medications. Race was dichotomized as "White" vs "non-White." Time to treatment initiation was determined from the date of the initial ILD registry visit to the date of first medication initiation. Proportions of treated patients were compared between groups by χ 2 test. Cox proportional analysis was used to determine how sex and race were associated with time to treatment initiation stratified by ILD diagnosis., Results: A total of 4,572 patients were included across all cohorts. The proportion of men who received treatment was higher than for women in the Canadian cohort (47% vs 40%; P < .001), and the proportion of White patients who received treatment was also higher compared with non-White patients (46% vs 36%; P < .001). In contrast, the proportion of treated men in the Chicago cohort was lower compared with women (56% vs 64%; P = .005), and that of White patients was lower compared with non-White patients (56% vs 69%; P < .001). No sex- or race-based differences in proportions of patients treated were found in the Australasian cohort. White race was significantly associated with earlier treatment initiation compared with non-White race across diagnoses in the Canadian cohort, whereas the opposite association was found in the Australasian cohort., Interpretation: Sex- and race-based differences exist in the initiation of ILD treatment, with variability across different cohorts in different countries. Reasons for these differences need to be further explored in future studies., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Part 2 of this 2-part CME introduces dermatologists to noninfectious inflammatory skin diseases associated with pulmonary involvement. In many cases, dermatologists may be the first physicians recognizing respiratory complications associated with these diagnoses. Because pulmonary involvement is often the leading cause of morbidity and mortality, dermatologists should be comfortable screening and monitoring for lung disease in high-risk patients, recognizing cutaneous stigmata of lung disease in these patients and referring to pulmonary specialists, when appropriate, for prompt treatment initiation. Some treatments used for skin disease may not be appropriate in the context of lung disease and hence, choosing a holistic approach is important. Interstitial lung disease and pulmonary hypertension are the most common pulmonary complications and a significant cause of mortality in autoimmune connective tissue diseases, especially systemic sclerosis, dermatomyositis, and mixed connective tissue disease. Pulmonary complications, notably interstitial lung disease, are also common and life-threatening in sarcoidosis and vasculitis, while they are variable in neutrophilic and autoimmune blistering diseases., Competing Interests: Conflicts of interest Gniadecki received lecture fees and advisory board honoraria from Mallinckrodt and Boehringer Ingelheim. Netchiporouk received lecture fees and advisory honoraria from Mallinckrodt and Boehringer Ingelheim. Ferrara received lecture fees and advisory board honoraria from Boehringer Ingelheim, Roche, and Astra Zeneca. Ouchene, Muntyanu, Assayag, Veilleux, Abril, Yacyshyn, Pineau, O'Brien, Baron, and Osman have no conflicts of interest to declare., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Fibrotic interstitial lung disease (ILD) includes a large group of conditions that lead to scarring of the lungs. The lack of available 5-level EuroQol 5D (EQ5D) data has limited the ability to conduct economic evaluations in ILD. The purpose of this study was to develop and validate a mapping algorithm that predicts EQ5D utilities from commonly collected pulmonary function measurements (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]) in fibrotic ILDs., Methods: EQ5D utility and pulmonary function measurements from the Canadian Registry for Pulmonary Fibrosis were included. Ordinary least squares (OLS), beta regression, two-part, and tobit models were used to map EQ5D utilities from FVC or DLCO. Model performance was assessed by comparing the predicted and observed utilities. Subgroup analyses were also conducted to test how well models performed across different patient characteristics. The models were then externally validated in the Australian Idiopathic Pulmonary Fibrosis Registry., Results: The OLS model performed as well as other more complex models (root mean squared error: 0.17 for FVC and 0.16 for DLCO). As with the other models, the OLS algorithm performed well across the different subgroups (except for EQ5D utilities < 0.5) and in the external validation cohort., Conclusion: We developed a mapping algorithm that predicts EQ5D utilities from FVC and DLCO, with the intent that this algorithm can be applied to clinical trial populations and real-world cohorts that have not prioritized collection of health-related utilities. The mapping algorithm can be used in future economic evaluations of potential ILD therapies., Competing Interests: Drs. Wong, Johannson, Marcoux, Assayag, Manganas, Kolb, Ryerson report personal fees and/or grants from Boehringer Ingelheim, outside the submitted work. Drs. Marcoux, Assayag, Kolb, and Ryerson report grants and/or personal fees from Roche Canada, outside the submitted work. Dr. Marcoux reports grants from AstraZeneca, outside the submitted work. Drs. Wong and Assayag report personal fees from AstraZeneca, outside the submitted work. Dr. Johannson reports grants from The Chest Foundation, University of Calgary Cumming School of Medicine, Pulmonary Fibrosis Society of Calgary, UCB Biopharma SPRL and personal fees from Blade Therapeutics, Theravance, Three Lakes Foundation, Pliant Therapeutics, and Hoffman-La Roche Ltd., outside the submitted work. Dr. Manganas reports grants from Galapagos, outside the submitted work. Dr. Kolb reports grants from Canadian Pulmonary Fibrosis Foundation, grants from Canadian Institute for Health Research, grants and personal fees from Prometic, other from European Respiratory Journal, personal fees from Third Pole, MitoImmune, Abbvie, DevPro Biopharma, Horizon, Algernon, CSL Behring, and grants and personal fees from Pieris, outside the submitted work. Dr. Ryerson reports personal fees from Pliant Therapeutics and Veracyte, outside the submitted work;. Drs. Sun, Cox, Fisher, Khalil, Palmer, de Graaff, Walters, Hopkins, Zappala, Goh, Moodley, Navaratnam, Corte, and Zhang report nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)