Search

Background: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC)., Objective: To investigate clinical laboratory markers of SARS-CoV-2 and PASC., Design: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024)., Setting: 83 enrolling sites., Participants: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection., Measurements: Participants completed questionnaires and standard clinical laboratory tests., Results: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 10 9 cells/L [95% CI, 264.5 to 267.4 × 10 9 cells/L]) than participants without known prior infection (275.2 × 10 9 cells/L [CI, 268.5 to 282.0 × 10 9 cells/L]), as well as higher mean hemoglobin A 1c (HbA 1c ) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA 1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero., Limitation: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined., Conclusion: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0737.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease that causes progressive cough, exertional dyspnea, impaired quality of life, and death. Objectives: Bexotegrast (PLN-74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. Methods: This Phase-2a multicenter, clinical trial randomized participants with IPF to receive, orally and once daily, bexotegrast at 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included change from baseline in FVC, quantitative lung fibrosis (QLF) extent (%), and changes from baseline in fibrosis-related biomarkers. Measurements and Main Results: Bexotegrast was well tolerated, with similar rates of TEAEs in the pooled bexotegrast and placebo groups (62/89 [69.7%] and 21/31 [67.7%], respectively). Diarrhea was the most common TEAE; most participants with diarrhea also received nintedanib. Participants who were treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared with those who received placebo, with or without background therapy. A dose-dependent antifibrotic effect of bexotegrast was observed with QLF imaging, and a decrease in fibrosis-associated biomarkers was observed with bexotegrast versus placebo. Conclusions: Bexotegrast demonstrated a favorable safety and tolerability profile, up to 12 weeks for the doses studied. Exploratory analyses suggest an antifibrotic effect according to FVC, QLF imaging, and circulating levels of fibrosis biomarkers. Clinical trial registered with www.clinicaltrials.gov (NCT04396756).

Objective: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease., Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation., Results: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs., Conclusion: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs., (© 2024 American College of Rheumatology.)

Objective: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs)., Methods: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations., Results: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs., Conclusion: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs., (© 2024 American College of Rheumatology.)

Background: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations., Methods: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population with AE-IPF, as defined by American Thoracic Society criteria, while excluding patients with an alternative cause for a respiratory decompensation. The primary endpoint of this trial is six-month survival. Secondary endpoints include supplement oxygen requirement and six-minute walk distance which will be assessed immediately prior to treatment and after completion of therapy on day 19, as well as at periodic subsequent visits., Discussion: The experimental AE-IPF therapy proposed in this clinical trial was adapted from treatment regimens used in other antibody-mediated diseases. The regimen is initiated with TPE, which is expected to rapidly reduce circulating autoantibodies, followed by rituximab to reduce B-cells and finally IVIG, which likely has multiple effects, including affecting feedback inhibition of residual B-cells by Fc receptor occupancy. We have reported potential benefits of this experimental therapy for AE-IPF in previous anecdotal reports. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF., Trial Registration: ClinicalTrials.gov identifier: NCT03286556., (© 2024. The Author(s).)

Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1 ) recommends the use of mycophenolate; 2 ) recommends further research into the safety and efficacy of ( a ) pirfenidone and ( b ) the combination of pirfenidone plus mycophenolate; and 3 ) suggests the use of ( a ) cyclophosphamide, ( b ) rituximab, ( c ) tocilizumab, ( d ) nintedanib, and ( e ) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.

What is this summary about? This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the American Journal of Respiratory and Critical Care Medicine in 2024. This study looked at a medicine called bexotegrast (beck-so-teh-grast) as a possible treatment for idiopathic pulmonary fibrosis (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). Bexotegrast is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment. IPF is a chronic, progressive lung disease that makes it hard to breathe and gets worse over time. There is no cure for IPF, treatment includes symptom management and consideration for the use of nintedanib or pirfenidone , which may decrease the pace of disease progression.The study compared bexotegrast to a placebo (a treatment that looks identical to the medicine but has no medicinal effect) to look at how well it works and how safe it is in treating people with IPF. Most people in the study also took one of two medicines that are already approved by the FDA for IPF, pirfenidone or nintedanib .

Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m 2 . However, there is no clear definition denoting severity of sarcoidosis-associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut-off values where transplant-free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant-free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan-Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut-off values where transplant-free survival was decreased. Decreased transplant-free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant-free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut-offs with decreased transplant-free survival in the SAPH population. Neither cut-off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant-free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. J. W. has received honoraria for lectures and advisory boards from Janssen (previously known as Actelion), Bayer, MSD and GSK. He has received travel grants from Janssen and GSK. He has received research grants from Bayer and Janssen. RPB has grant support from Gilead, Bayer, Actelion, Genentech, aTyr, Novartis, and Bellephron for studies in sarcoidosis. O. A. S. consults for and is a speaker for Bayer, United Therapeutics, and Janssen & Janssen. She also consults for Altavant. L. C. P. declares personal fees from Janssen Pharmaceuticals, outside the submitted work. SB has received consultancy fees from aTy and Kinevant. S. D. N. is a consultant for Boehringer‐Ingelheim, Roche, United Therapeutics, Bellerophon, Third Pole, and Merck. He is on the speakers bureau for Boehringer‐Ingelheim and United Therapeutics. R. G. has received consultancy fees from Mallinckrodt. This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors. The remaining author declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Climate change adversely impacts global health. Increasingly, temperature variability, inclement weather, declining air quality, and growing food and clean water supply insecurities threaten human health. Earth's temperature is projected to increase up to 6.4 °C by the end of the 21st century, exacerbating the threat. Public and health care professionals, including pulmonologists, perceive the detrimental effects of climate change and air pollution and support efforts to mitigate its effects. In fact, evidence is strong that premature cardiopulmonary death is associated with air pollution exposure via inhalation through the respiratory system, which functions as a portal of entry. However, little guidance is available for pulmonologists in recognizing the effects of climate change and air pollution on the diverse range of pulmonary disorders. To educate and mitigate risk for patients competently, pulmonologists must be armed with evidence-based findings of the impact of climate change and air pollution on specific pulmonary diseases. Our goal is to provide pulmonologists with the background and tools to improve patients' health and to prevent adverse outcomes despite climate change-imposed threats. In this review, we detail current evidence of climate change and air pollution impact on a diverse range of pulmonary disorders. Knowledge enables a proactive and individualized approach toward prevention strategies for patients, rather than merely treating ailments reactively., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Interstitial lung disease is a known complication of rheumatoid arthritis, with a lifetime risk of developing the disease in any individual of 7·7%. We aimed to assess the safety, tolerability, and efficacy of pirfenidone for the treatment of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD)., Methods: TRAIL1 was a randomised, double-blind, placebo-controlled, phase 2 trial done in 34 academic centres specialising in interstitial lung disease in four countries (the UK, the USA, Australia, and Canada). Adults aged 18-85 years were eligible for inclusion if they met the 2010 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis and had interstitial lung disease on a high-resolution CT scan imaging and, when available, lung biopsy. Exclusion criteria include smoking, clinical history of other known causes of interstitial lung disease, and coexistant clinically significant COPD or asthma. Patients were randomly assigned (1:1) to receive 2403 mg oral pirfenidone (pirfenidone group) or placebo (placebo group) daily. The primary endpoint was the incidence of the composite endpoint of a decline from baseline in percent predicted forced vital capacity (FVC%) of 10% or more or death during the 52-week treatment period assessed in the intention-to-treat population. Key secondary endpoints included change in absolute and FVC% over 52 weeks, the proportion of patients with a decline in FVC% of 10% or more, and the frequency of progression as defined by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02808871., Findings: From May 15, 2017, to March 31, 2020, 231 patients were assessed for inclusion, of whom 123 patients were randomly assigned (63 [51%] to the pirfenidone group and 60 [49%] to the placebo group). The trial was stopped early (March 31, 2020) due to slow recruitment and the COVID-19 pandemic. The difference in the proportion of patients who met the composite primary endpoint (decline in FVC% from baseline of 10% or more or death) between the two groups was not significant (seven [11%] of 63 patients in the pirfenidone group vs nine [15%] of 60 patients in the placebo group; OR 0·67 [95% CI 0·22 to 2·03]; p=0·48). Compared with the placebo group, patients in the pirfenidone group had a slower rate of decline in lung function, measured by estimated annual change in absolute FVC (-66 vs -146; p=0·0082) and FVC% (-1·02 vs -3·21; p=0·0028). The groups were similar with regards to the decline in FVC% by 10% or more (five [8%] participants in the pirfenidone group vs seven [12%] in the placebo group; OR 0·52 [95% CI 0·14-1·90]; p=0·32) and the frequency of progression as defined by OMERACT (16 [25%] in the pirfenidone group vs 19 [32%] in the placebo group; OR 0·68 [0·30-1·54]; p=0·35). There was no significant difference in the rate of treatment-emergent serious adverse events between the two groups, and there were no treatment-related deaths., Interpretation: Due to early termination of the study and underpowering, the results should be interpreted with caution. Despite not meeting the composite primary endpoint, pirfenidone slowed the rate of decline of FVC over time in patients with RA-ILD. Safety in patients with RA-ILD was similar to that seen in other pirfenidone trials., Funding: Genentech., Competing Interests: Declaration of interests SKD reports grants and salary support from Brigham and Women's Hospital, during the study; grants, personal fees, and non-financial support from Boehringer Ingelheim; personal fees and non-financial support from Galaplagos; personal fees from Galecto, and Lupin Pharma; grants from Bristol Meyers Squibb; salary support from the Pulmonary Fibrosis Foundation, and Royalties for Topics on systemic erythematous pneumonia- interstitial lung disease and myositis- interstitial lung disease from UpToDate, outside the submitted work. IG reports personal fees from Boehringer Ingelheim and personal fees from Ad Alta, Amplia, Accendatech, and Lassen, outside the submitted work. PFD served on an unpaid advisory committee at Boehringer Ingleheim, and reports receiving non-financial support for serving as a site-principal investigator for Bristol Myers and Genentech, outside the submitted work. RV reports grants from Bristol Myers Squibb, Pfizer, and Sun Pharma, outside the submitted work. PGC reports grants from InterMune, outside the submitted work. KRF reports grants and personal fees from Boehringer Ingelheim; personal fees from Roche/Genentech, Bellerophon, Respivant, Shionogi, DevPro, AstraZeneca, Pure Health, Horizon, Fibrogen, Sun Pharmaceuticals, Pliant, United Therapeutics, Arrowhead, Lupin, Polarean, Pure Tech, Trevi Pharmaceuticals, CSL Behring, Daewong, DevPro, Dispersol, Immumet, and NeRRe Therapeutics, outside the submitted work. LT reports personal fees from Boehringer Ingelheim outside the submitted work. MBS reports grants from Boehringer Ingelheim, Veracyte, and Genentech; financial support from Genentech, United Therapeutics, Veracyte; honoraria from Boehringer Ingelheim, United Therapeutics, and Veracyte, and meeting and travel support from Genentech and the American College of Chest Physicians. NC reports personal fees from Boehringer Ingelheim, Redex, Novartis, Liminal Biosciences, Vicor Pharma, Bridge Biotherapeutics, and Roche, outside the submitted work. DAL reports grants from Boehringer Ingelheim and grants and personal fees from Calyx, outside the submitted work; DAL has a patent issued on systems and methods for automatic detection and quantification of pathology using dynamic feature classification (US10706533B2). DCC reports that Roche/Genentech provided the investigational medicinal product free of charge during the study; and that he served as principal investigator for a trial site in a Roche sponsored study outside the submitted work, in which per patient fees were paid to the site. MK reports grants from Genentech, during the study; grants from Canadian Pulmonary Fibrosis Foundation and Canadian Institute for Health Research; an allowance as chief editor from European Respiratory Journal; grants and personal fees from Boehringer Ingelheim and Roche Canada; and personal fees from Horizon, Algernon, CSL Behring, and DevPro; and served as a site principal investigator for industry sponsored clinical trials (Roche and Boehringer Ingelheim); outside the submitted work. GR served as a consultant/steering committee member for IPF and PPF studies for Roche/Genentech and served on a data safety monitoring board for an IPF study (Avalyn), outside the submitted work. HJG reports receiving support to participate as a member of the Clinical Coordinating Center and coprincipal investigator, from Genentech, during the study. FAW is currently an employee at Avalyn. IOR reports grants from Genentech/Roche, during the conduct of the study and personal fees from Genentech/Roche, Boehringer Ingelheim, and Immunomet, outside the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization (WHO) introduced the International Classification of Functioning, Disability, and Health (ICF) as a scientific method of disability data collection comprised of >1,200 categories describing the spectrum of impairment types (functional, symptoms-based and anatomical) under the bio-psycho-social model with consideration of environmental and personal factors (pf). ICF Core Sets and ICF Checklists are streamlined disease-specific resources for clinical use, service provision, and for use in health economics and health policy. ICF can disclose strengths and weaknesses across multiple patient-reported outcome measures (PROMs) and help consolidate best-fitting question-items from multiple PROMs. Interstitial lung diseases (ILDs), are generally progressive, with restrictive physiology sometimes occurring in the context of multi-organ autoimmunity/inflammatory conditions such as connective tissue diseases (CTDs). In spite of significant associated morbidity and potential disability, ILD has yet to be linked to the ICF. Methods: Each instrument and their question-items within the consensus-recommended core sets for clinical trials in ILD were deconstructed to single concept units, and then linked per updated ICF linkage rules. Inter-linker agreement was established. Three additional subsequently validated measures were also included. Results: One-hundred-eleven ICF categories were identified for ten PROMs and three traditional objective measures that were amenable to ICF linkage. The proportion of agreement ranged from 0.79 (95% CI: 0.62, 0.91) to 0.93 (0.76, 0.99) with the overall proportion of inter-linker agreement being very high 0.86 (0.82, 0.89) for the initial instruments, with 94-100% for the three additional PROMs. Thirty-four new 'Personal Factors' emerged to capture disease-specific qualities not elsewhere described in ICF, e.g. 'pf_embarrassed by cough' or 'pf_panic/afraid when can't get a breath'. Conclusion: This first known effort in ICF linkage of ILD has provided important revelations on the current utility of the ICF in lung disease. Results have indicated areas for meaningful assessment of ICF descriptors for lung impairment. The mapping across PROMs provides insight into possibilities of developing more streamline and precise instrumentation. Finally, familiarity with the ICF in ILD may enable clinicians to experience a smoother transition with the imminent harmonization of ICD and ICF, ICD-11., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saketkoo, Escorpizo, Varga, Keen, Fligelstone, Birring, Alexanderson, Pettersson, Chaudhry, Poole, Regardt, LeSage, Sarver, Lanario, Renzoni, Scholand, Lammi, Kowal-Bielecka, Distler, Frech, Shapiro, Varju, Volkmann, Bernstein, Drent, Obi, Patterson, Russell and The Global Fellowship on Rehabilitation and Exercise in Systemic Sclerosis (G-FoRSS).)

Background: Cough is a common symptom of interstitial lung disease (ILD) and negatively impacts health-related quality of life (QOL). Previous studies have shown that among patients with idiopathic pulmonary fibrosis, cough may predict progression of lung disease and perhaps even respiratory hospitalizations and mortality., Research Question: Does cough-specific QOL predict disease progression, respiratory hospitalization, lung transplantation, and death among patients with ILD?, Study Design and Methods: We analyzed data from the Pulmonary Fibrosis Foundation Registry, which comprises a multicenter population of well-characterized patients with ILD. We first examined associations between patient factors and baseline scores on the Leicester Cough Questionnaire (LCQ), a cough-specific QOL tool, using a proportional odds model. Next, we examined associations between baseline LCQ scores and patient-centered clinical outcomes, as well as pulmonary function parameters, using a univariable and multivariable proportional hazards model that was adjusted for clinically relevant variables, including measures of disease severity., Results: One thousand four hundred forty-seven patients with ILD were included in our study. In the multivariable proportional odds model, we found that the following patient factors were associated with worse cough-specific QOL: younger age, diagnosis of "other ILD," gastroesophageal reflux disease, and lower FVC % predicted. Multivariable Cox regression models, adjusting for several variables including baseline disease severity, showed that a 1-point decrease in LCQ score (indicating lower cough-specific QOL) was associated with a 6.5% higher risk of respiratory-related hospitalization (hazard ratio [HR], 1.065; 95% CI, 1.025-1.107), a 7.4% higher risk of death (HR, 1.074; 95% CI, 1.020-1.130), and an 8.7% higher risk of lung transplantation (HR, 1.087; 95% CI, 1.022-1.156)., Interpretation: Among a large population of well-characterized patients with ILD, cough-specific QOL was associated independently with respiratory hospitalization, death, and lung transplantation., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD) and is associated with worse outcomes and increased mortality. Evaluation of PH is recommended in lung transplant candidates, but there are currently no standardized screening approaches. Trials have identified therapies that are effective in this setting, providing another rationale to routinely screen patients with ILD for PH., Research Question: What screening strategies for identifying PH in patients with ILD are supported by expert consensus?, Study Design and Methods: The study convened a panel of 16 pulmonologists with expertise in PH and ILD, and used a modified Delphi consensus process with three surveys to identify PH screening strategies. Survey 1 consisted primarily of open-ended questions. Surveys 2 and 3 were developed from responses to survey 1 and contained statements about PH screening that panelists rated from -5 (strongly disagree) to 5 (strongly agree)., Results: Panelists reached consensus on several triggers for suspicion of PH including the following: symptoms, clinical signs, findings on chest CT scan or other imaging, abnormalities in pulse oximetry, elevations in brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP), and unexplained worsening in pulmonary function tests or 6-min walk distance. Echocardiography and BNP/NT-proBNP were identified as screening tools for PH. Right heart catheterization was deemed essential for confirming PH., Interpretation: Many patients with ILD may benefit from early evaluation of PH now that an approved therapy is available. Protocols to evaluate patients with ILD often overlap with evaluations for pulmonary hypertension-interstitial lung disease and can be used to assess the risk of PH. Because standardized approaches are lacking, this consensus statement is intended to aid physicians in the identification of patients with ILD and possible PH, and provide guidance for timely right heart catheterization., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: The diagnosis of idiopathic pulmonary fibrosis (IPF) remains challenging and can result in delayed or misdiagnosis. IPF diagnosis is based on the presence of either a radiographic or histologic usual interstitial pneumonia (UIP) pattern in the absence of an identifiable etiology. The Envisia Genomic Classifier is a clinically validated molecular diagnostic test that identifies UIP in transbronchial biopsies. Objectives: To determine the impact of the Envisia Genomic Classifier on physicians' clinical decision-making in the diagnosis and management of IPF. Methods: This prospective randomized decision impact survey was designed to test the hypothesis that including an Envisia UIP-positive result will increase IPF diagnoses, diagnostic confidence, and the recommendation for antifibrotic therapy. The survey included patients from the BRAVE (Bronchial Sample Collection for a Novel Genomic Test) study who had a high-resolution computed tomographic scan without a typical UIP pattern, an Envisia UIP-positive result, and a final diagnosis of IPF by multidisciplinary team discussion. Each case was presented in three different formats: a pre-post cohort, where each case is presented initially without and then with Envisia, and two independent cohorts, where each case is presented without and with Envisia, respectively. Results: U.S.-based pulmonologists from community and academic centers in geographically diverse practices were approached for inclusion in this study. 103 (65%) U.S.-based pulmonologists met the inclusion criteria and provided 605 case reviews of 11 patient cases. The number of IPF diagnoses increased with Envisia by an absolute difference of 39% from 47 (30%) before Envisia to 107 (69%) after Envisia in the pre-post cohort and by 13% in the independent cohorts. High confidence (⩾90%) of interstitial lung disease diagnoses was more commonly seen with Envisia in both the pre-post cohort and in the independent cohorts. Recommendation for antifibrotic treatment increased with Envisia by an absolute difference of 36% from 15 (10%) before Envisia to 72 (46.4%) after Envisia in the pre-post cohort and by 11% in the independent cohorts. Conclusions: This decision impact survey suggests the clinical utility of the Envisia Classifier by demonstrating a significant increase in IPF diagnoses, diagnostic confidence, and recommendation for antifibrotic therapies to assist physicians in effectively managing patients to improve outcomes of patients with IPF.

Introduction: Sarcoidosis associated pulmonary hypertension (SAPH) is a leading contributor to sarcoidosis-related mortality. The 6-min walk test (6MWT) is widely used in assessment of cardiorespiratory conditions. A reduced 6-min walk distance (6MWD) has been associated with increased mortality in SAPH. We examined patients from the Registry of Sarcoidosis Associated Pulmonary Hypertension (ReSAPH) who had performed 6MWT at enrollment to identify variables that affect 6MWD, and the prognostic value of 6MWT variables regarding death or lung transplantation., Material and Methods: ReSAPH patients with available 6MWT were included. Variables analyzed using pre-defined cutoffs included 6MWD, initial and end of test Borg dyspnea score, oxygen saturation, and heart rate at beginning, end, and after 1-min recovery, absolute change in oxygen saturation, modified distance-saturation product (mDSP), and the heart rate recovery at 1-min (HRR)., Findings: 174 patients met inclusion criteria; 48 patients died and 8 underwent lung transplantation. Patients with 6MWD<300 m had a higher chance of dying or undergoing transplantation compared to those with 6MWD>300 m (p = 0.012). No associations with outcome were observed with mDSP cutoff 200 m%, desaturation≥5% and oxygen saturation<88% at end of 6MWT, or multiple HRR cutoffs (13,14,16). 6MWD correlated with initial Borg score, (p = 0.001), DLCO% (p = 0.0001) and sPAP (p = 0.031) on multivariate analysis. These variables were significant for both pre- and post-capillary PH subgroups. 6MWD also correlated with fatigue assessment scale (FAS) (p = 0.015)., Conclusion: Of the parameters evaluated, 6MWD had the greatest prognostic value in SAPH which correlated with other physiologic and hemodynamic variables. 6MWT captures the multidimensional effects of sarcoidosis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Echocardiographic measurement of the right ventricular systolic pressure (RVSP) is commonly used for estimating systolic pulmonary artery pressure (PASP) measured during right heart catheterization (RHC) in patients suspected for pulmonary hypertension (PH). Generally, there seems to be a strong correlation. However, this has been reported as less robust in sarcoidosis. We aim to investigate the correlation between RVSP and RHC measurements using real world data and analyzed factors influencing the relationship between RVSP and PASP in sarcoidosis., Methods & Results: Data of patients with and without sarcoidosis associated PH who had both a measurable echocardiographic RVSP and invasive PASP were collected from the RESAPH registry, PULSAR study and Cincinnati Sarcoidosis Clinic database (n=173, 60.1% female, mean age 56.0±9.5 years). Among them, 124 had PH confirmed by RHC. There was a strong correlation between RVSP and PASP (r=0.640). This correlation was significant in both male and female, white or non-white, forced vital capacity (FVC) >60%, and presence of fibrosis (p<0.001). However, it was less robust in patients with FVC of 50% or less. RVSP was considered inaccurate if the difference with PASP was > 10mmHg. Inaccurate echocardiographic estimation of the invasive PASP occurred in 50.8%, with overestimation mostly in patients without PH, and underestimation in patients with severe PH. An RVSP>50mmHg was associated with worse survival., Conclusions: In this real world multicenter cohort of sarcoidosis patients, we found a significant correlation between RVSP as determined by echocardiography and invasive PASP. Over- or underestimation of PASP occurred frequently. Therefore, echocardiographic RVSP measurement alone to screen for PH in sarcoidosis should be used with caution., (Copyright: © 2021 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Systemic sclerosis (SSc) is a heterogeneous multisystem autoimmune disease whereby its main pathological drivers of disability and damage are vascular injury, inflammatory cell infiltration, and fibrosis. These mechanisms result in diffuse and diverse impairments arising from ischemic circulatory dysfunction leading to painful skin ulceration and calcinosis, neurovascular aberrations hindering gastrointestinal (GI) motility, progressive painful, incapacitating or immobilizing effects of inflammatory and fibrotic effects on the lungs, skin, articular and periarticular structures, and muscle. SSc-related impairments impede routine activities of daily living (ADLs) and disrupt three critical life areas: work, family, social/leisure, and also impact on psychological well-being. Physical activity and exercise are globally recommended; however, for connective tissue diseases, this guidance carries greater impact on inflammatory disease manifestations, recovery, and cardiovascular health. Exercise, through myogenic and vascular phenomena, naturally targets key pathogenic drivers by downregulating multiple inflammatory and fibrotic pathways in serum and tissue, while increasing circulation and vascular repair. G-FoRSS, The Global Fellowship on Rehabilitation and Exercise in Systemic Sclerosis recognizes the scientific basis of and advocates for education and research of exercise as a systemic and targeted SSc disease-modifying treatment. An overview of biophysiological mechanisms of physical activity and exercise are herein imparted for patients, clinicians, and researchers, and applied to SSc disease mechanisms, manifestations, and impairment. A preliminary guidance on exercise in SSc, a research agenda, and the current state of research and outcome measures are set forth., Competing Interests: Declaration of competing interest None of the authors have conflicts to disclose in relation to this publication., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to report that are related to the reported content of this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The purpose of this summary is to provide a synopsis of evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability., Study Design and Methods: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, and Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus., Results: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations, and 2 ungraded consensus-based statements. All evidence was of very low quality., Interpretation: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this analysis is to provide evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability., Study Design and Methods: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. A diagnostic algorithm is provided, using supporting data from the recommendations where possible, along with expert consensus to help physicians gauge the probability of HP., Results: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations and 2 ungraded consensus-based statements. All evidence was of very low quality., Interpretation: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Criteria are presented to facilitate diagnosis of HP. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Health-related quality of life (HRQoL), though rarely considered as a primary endpoint in clinical trials, may be the single outcome reflective of patient priorities when living with a health condition. HRQoL is a multi-dimensional concept that reflects the degree to which a health condition interferes with participation in and fulfillment of important life areas. HRQoL is intended to capture the composite degree of physical, physiologic, psychological, and social impairment resulting from symptom burden, patient-perceived disease severity, and treatment side effects. Diminished HRQoL expectedly correlates to worsening disability and death; but interventions addressing HRQoL are linked to increased survival . Sarcoidosis, being a multi-organ system disease, is associated with a diffuse array of manifestations resulting in multiple symptoms, complications, and medication-related side effects that are linked to reduced HRQoL. Diminished HRQoL in sarcoidosis is related to decreased physical function, pain, significant loss of income, absence from work, and strain on personal relationships. Symptom distress can result clearly from a sarcoidosis manifestation (e.g., ocular pain, breathlessness, cough) but may also be non-specific, such as pain or fatigue. More complex, a single non-specific symptom, e.g., fatigue may be directly sarcoidosis-derived (e.g., inflammatory state, neurologic, hormonal, cardiopulmonary), medication-related (e.g., anemia, sleeplessness, weight gain, sub-clinical infection), or an indirect complication (e.g., sleep apnea, physical deconditioning, depression). Identifying and distinguishing underlying causes of impaired HRQoL provides opportunity for treatment strategies that can greatly impact a patient's function, well-being, and disease outcomes. Herein, we present a reference manual that describes the current state of knowledge in sarcoidosis-related HRQoL and distinguish between diverse causes of symptom distress and other influences on sarcoidosis-related HRQoL. We provide tools to assess, investigate, and diagnose compromised HRQoL and its influencers. Strategies to address modifiable HRQoL factors through palliation of symptoms and methods to improve the sarcoidosis health profile are outlined; as well as a proposed research agenda in sarcoidosis-related HRQoL.

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis., Objective: To assess the effect of antimicrobial therapy on clinical outcomes., Design, Setting, and Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020)., Interventions: Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). No placebo was administered in the usual care alone group., Main Outcomes and Measures: The primary end point was time to first nonelective respiratory hospitalization or all-cause mortality., Results: Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%)., Conclusions and Relevance: Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease., Trial Registration: ClinicalTrials.gov Identifier: NCT02759120.

This phase 2, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of lebrikizumab, an interleukin (IL)-13 monoclonal antibody, alone or with background pirfenidone therapy, in patients with idiopathic pulmonary fibrosis (IPF).Patients with IPF aged ≥40 years with forced vital capacity (FVC) of 40%-100% predicted and diffusing capacity for carbon monoxide of 25%-90% predicted and who were treatment-naïve (cohort A) or receiving pirfenidone (2403 mg·day -1 ; cohort B) were randomised 1:1 to receive lebrikizumab 250 mg or placebo subcutaneously every 4 weeks. The primary endpoint was annualised rate of FVC % predicted decline over 52 weeks.In cohort A, 154 patients were randomised to receive lebrikizumab (n=78) or placebo (n=76). In cohort B, 351 patients receiving pirfenidone were randomised to receive lebrikizumab (n=174) or placebo (n=177). Baseline demographics were balanced across treatment arms in both cohorts. The primary endpoint (annualised rate of FVC % predicted decline) was not met in cohort A (lebrikizumab versus placebo, -5.2% versus -6.2%; p=0.456) or cohort B (lebrikizumab versus placebo, -5.5% versus -6.0%; p=0.557). In cohort B, a non-statistically significant imbalance in mortality favouring combination therapy was observed (hazard ratio 0.42 (95% CI 0.17-1.04)). Pharmacodynamic biomarkers indicated lebrikizumab activity. The safety profile was consistent with that in previous studies of lebrikizumab and pirfenidone as monotherapies.Lebrikizumab alone or with pirfenidone was not associated with reduced FVC % predicted decline over 52 weeks despite evidence of pharmacodynamic activity. Lebrikizumab was well tolerated with a favourable safety profile. These findings suggest that blocking IL-13 may not be sufficient to achieve a lung function benefit in patients with IPF., Competing Interests: Conflict of interest: T.M. Maher reports grants from GlaxoSmithKline and University of California, Berkeley (UCB), during the conduct of the study; and he served as a consultant and speaker for Apellis, AstraZeneca, Bayer, Blade Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Indalo, Novartis, Pliant, ProMetic, Respivnat, Roche, Samumed and UCB. Conflict of interest: U. Costabel was a member of a study adjudication committee for Gilead; has served as a consultant and speaker for Bayer, Boehringer Ingelheim and InterMune/Roche; has received grants from Boehringer Ingelheim and InterMune and has served as a consultant for Centocor, Fibrogen, Gilead, GlaxoSmithKline, UCB Celltech and Biogen. Conflict of interest: M.K. Glassberg reports grants from Genentech/Roche during the conduct of the study; was a member of the ASCEND study steering committee; and has served as a consultant for Bellerophon, Boehringer Ingelheim, Bristol Myers Squibb, InterMune, RedX Pharma and Roche. Conflict of interest: Y. Kondoh reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study and has served as a consultant for Genentech and has served as a consultant and speaker for Asahi Kasei, Boehringer Ingelheim, Eisai, Janssen, Kyorin, Mitsubishi Tanabe Pharma, Novartis and Shionogi. Conflict of interest: T. Ogura reports grants from Boehringer Ingelheim and the Ministry of Health, Labour and Welfare, Japan, during the conduct of the study and has served as a consultant or speaker for Asahi Kasei, Boehringer Ingelheim, Eisai, Nitto Denko, Shionogi and Toray. Conflict of interest: M.B. Scholand has served on advisory boards for Boehringer Ingelheim and InterMune/Roche/Genentech. Conflict of interest: D. Kardatzke is an employee of Genentech, Inc. Conflict of interest: M. Howard is an employee of Genentech, Inc. Conflict of interest: J. Olsson is an employee of Genentech, Inc. Conflict of interest: M. Neighbors is an employee of Genentech, Inc. Conflict of interest: P. Belloni is an employee of Genentech, Inc. Conflict of interest: J.J. Swigris reports grants from InterMune, personal fees from Genentech, Inc., during the conduct of the study; was a member of the ASCEND study steering committee; served on a scientific advisory board for InterMune and served as a consultant to Boehringer Ingelheim and Roche., (Copyright ©ERS 2021.)

Rationale: Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A "molecular diagnosis of UIP" in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP. Objectives: We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern. Methods: Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology. Measurements and Main Results: In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval [CI],78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%). Conclusions: In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.

Rationale: Several new drugs for idiopathic pulmonary fibrosis (IPF) are in development. Tools are needed to assess whether these drugs benefit patients on outcomes that matter most to them. Health-related quality of life (HRQL) is one such outcome. It is influenced by many factors, but symptoms and their impacts are two strong drivers. Objectives: To develop a questionnaire to assess symptoms, disease impacts, and HRQL specifically for patients with IPF. Methods: Working with the U.S. Food and Drug Administration through the Drug Development Tool Qualification process, focus groups, concept elicitation, and cognitive debriefing interviews were conducted to inform the development of a 44-item pilot questionnaire. The pilot paper-and-pen questionnaire was migrated to an equivalent electronic version and field-tested in a 14-day study. Response data were subjected to psychometric testing, including exploratory factor analysis, item calibration using item response theory models, test-retest reliability, and validity testing. Measurements and Main Results: A total of 125 patients with IPF (62.4% men) completed the longitudinal study. The mean ± SD age of the cohort was 69 ± 7.60 years, and the mean FVC% predicted was 71 ± 20.0. After factor and item analyses, 35 items were retained, and these comprise the two modules (symptoms and impacts) of the Living with IPF (L-IPF) questionnaire. The L-IPF yields five scales demonstrating good psychometric properties, including correlation with concurrently collected FVC% predicted and the ability to discriminate between patients with differing levels of IPF severity. Conclusions: The L-IPF is a new questionnaire that assesses symptoms, disease impacts, and HRQL in patients with IPF.

Background: In patients with idiopathic pulmonary fibrosis (IPF) treated with pirfenidone (Esbriet®, Genentech USA, Inc. South San Francisco, CA.), effectively managing treatment-related adverse events (AEs) may improve adherence. Due to a lack of clinical evidence and expertise, managing these AEs can be challenging for patients and physicians alike. In the absence of evidence, consensus recommendations from physicians experienced in using pirfenidone to treat IPF are beneficial., Methods: Using a modified Delphi process, expert recommendations were developed by a panel of physicians experienced with using pirfenidone for IPF. Over three iterations, panelists developed and refined a series of statements on the use of pirfenidone in IPF. Their agreement on each statement was ranked using a Likert scale., Results: A panel of 12 physicians participated and developed a total of 286 statements on dosing and administration, special populations, drug-drug interactions, laboratory analysis, warnings and precautions, and AE management. Expert recommendations were achieved with regard to slower initial titrations and slower titrations for AEs, dosing with meal(s) or substantial meals, and adding other prescribed pharmacological agents for AEs., Conclusion: Until there is further clinical evidence, the resulting consensus recommendations are intended to provide direction on the practical management of IPF with pirfenidone, by encompassing a broad experience from the real world to complement data gleaned from clinical trials.

Introduction: Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with reduced survival in single-centre studies. The international Registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients., Methods: ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrolment. Information analysed includes right heart catheterisation data, pulmonary function testing, chest radiography, Scadding stage and 6-min walk distance (6MWD), among others. Cox regression models were used to identify independent predictors of transplant-free survival., Results: Data from 215 patients followed for a mean±sd 2.5±1.9 years were available for analysis. In the 159 precapillary patients, the Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival was 89.2%, 71.7% and 62.0%, respectively. Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival in the incident group was 83.5%, 70.3% and 58.3%, respectively, and in the prevalent group was 94.7%, 72.2% and 66.3%, respectively. Patients with reduced diffusing capacity of the lung for carbon monoxide ( D LCO ) (<35% predicted) and 6MWD <300 m in the precapillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved forced expiratory volume (FEV 1 )/forced vital capacity (FVC) ratio were identified as independent risk factors for reduced transplant-free survival in the precapillary cohort., Conclusion: Reduced D LCO (<35% pred) and 6MWD (<300 m) at the time of registry enrolment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV 1 /FVC ratio was identified as an independent risk factor for worsened outcomes., Competing Interests: Conflict of interest: O.A. Shlobin reports personal fees for consultancy from United Therapeutics, Bayer and Johnson & Johnson, outside the submitted work. Conflict of interest: V. Kouranos has nothing to disclose. Conflict of interest: S.D. Barnett has nothing to disclose. Conflict of interest: E.H. Alhamad has nothing to disclose. Conflict of interest: D.A. Culver reports institutional funding for the registry from Gilead, during the conduct of the study; personal fees for advisory board work from Johnson and Johnson, outside the submitted work. Conflict of interest: J. Barney has nothing to disclose. Conflict of interest: F.C. Cordova has nothing to disclose. Conflict of interest: E.M. Carmona reports financial support for the clinical trial from Gilead, during the conduct of the study; personal fees for consultancy and developing education materials from CHEST, personal fees for editorial work from Elsevier, outside the submitted work. Conflict of interest: M.B. Scholand has performed advisory board work and been investigator in clinical trials for Boehringer Ingelheim and Genentech, and been investigator in clinical trials for Fibrogen and Global Blood Therapeutics, outside the submitted work; and has a patent Apparatus, Compositions and Methods for Assessment of Chronic Obstructive Pulmonary Disease Progression among Rapid and Slow Decline Conditions issued. Conflict of interest: M. Wijsenbeek has nothing to disclose. Conflict of interest: S. Ganesh has nothing to disclose. Conflict of interest: E.E. Lower reports grants from Gilead, Bayer and Genentech, during the conduct of the study. Conflict of interest: P.J. Engel has nothing to disclose. Conflict of interest: J. Wort reports grants and personal fees from Actelion Pharmaceuticals and Bayer Pharmaceuticals, personal fees from MSD, outside the submitted work. Conflict of interest: L. Price reports personal fees and education support from Actelion and Johnson & Johnson, during the conduct of the study. Conflict of interest: A.U. Wells reports personal fees from Boehringer Ingelheim, Roche, Intermune and Bayer, outside the submitted work. Conflict of interest: S.D. Nathan reports personal fees for consultancy from United Therapeutics, Bayer Pharmaceuticals, Bellerophon and Actelion, during the conduct of the study. Conflict of interest: R.P. Baughman reports grants from Gilead, Bayer, Genentech, Foundation for Sarcoidosis Research and National Institutes of Health, grants and personal fees for consultancy from Actelion, grants and personal fees for consultancy and lectures from Mallinckrodt, during the conduct of the study., (Copyright ©ERS 2020.)

A variety of phenotypic categorisations have been developed for sarcoidosis. Phenotyping has been used for genetics studies and to guide treatment selection. The authors participated in a Delphi expert consensus panel to develop a proposed phenotype categorisation and treatment recommendations for pulmonary sarcoidosis patients. Panellists reached consensus that asymptomatic patients with normal pulmonary function and adenopathy alone or normal chest imaging do not require therapy, while symptomatic patients with impaired pulmonary function or infiltrates should be treated. The panel did not reach consensus on asymptomatic patients with abnormal chest imaging or reduced pulmonary function, or symptomatic patients with normal chest imaging and pulmonary function. The proposed phenotype categories and associated treatment recommendations are asymptomatic (no therapy), acute (disease duration <1-2 years, apparently self-limited, corticosteroids), chronic (antimetabolites and other second-line therapies) and advanced (biologics). Some clinical settings, such as dyspnoea/hypoxaemia at rest, severely impaired or rapidly decreasing pulmonary function tests, and severe cardiac, neurologic, ocular or renal involvement warrant immediate therapy., Competing Interests: Conflict of interest: R.P. Baughman reports grants and personal fees from Malllinckrodt, Novartis and Celgene, grants from Gilead, Genentech and Bayer, and personal fees from West Pharmaceutical, during the conduct of the study. Conflict of interest: M.B. Scholand reports other from Boehringer Ingelheim, Genentech, Fibrogen and Global Blood Therapeutics, outside the submitted work. In addition, M.B. Scholand has a patent Apparatus, Compositions and Methods for Assessment of Chronic Obstructive Pulmonary Disease Progression among Rapid and Slow Decline Conditions issued. Conflict of interest: F.F. Rahaghi reports grants and consulting fees from Mallinckrodt, during the conduct of the study., (Copyright ©ERS 2020.)

In patients treated with repository corticotrophin injection (RCI) for pulmonary sarcoidosis, effective management of adverse events may improve adherence. However, management of adverse events may be challenging due to limitations in real-world clinical experience with RCI and available published guidelines.We surveyed 12 physicians with a modified Delphi process using three questionnaires. Questionnaire 1 consisted of open-ended questions. Panellists' answers were developed into a series of statements for Questionnaires 2 and 3. In these, physicians rated their agreement with the statements using a Likert scale.Key consensus recommendations included a starting dose of 40 units twice a week for patients with less severe disease, continued at a maintenance dose for patients who responded, particularly those with chronic refractory sarcoidosis. Panellists reached consensus that concomitant steroids should be quickly tapered in patients receiving RCI, but that concomitant use of immunosuppressive medications should be continued. Panellists developed consensus recommendations for adverse event management, and reached consensus that RCI should be down-titrated or discontinued if other interventions for the adverse effects fail or if the adverse effect is severe.In the absence of clinical evidence, our Delphi consensus opinions may provide practical guidance to physicians on the management of RCI to treat pulmonary sarcoidosis., Competing Interests: Conflict of interest: F.F. Rahaghi reports grants and consulting fees from Mallinckrodt, during the conduct of the study. Conflict of interest: N.J. Sweiss has nothing to disclose. Conflict of interest: L.A. Saketkoo has nothing to declare. Conflict of interest: M.B. Scholand reports other from Boehringer Ingelheim, Genentech, Fibrogen and Global Blood Therapeutics, outside the submitted work. In addition, M.B. Scholand has a patent Apparatus, Compositions and Methods for Assessment of Chronic Obstructive Pulmonary Disease Progression among Rapid and Slow Decline Conditions issued. Conflict of interest: J.B. Barney has nothing to disclose. Conflict of interest: A.K. Gerke has nothing to disclose. Conflict of interest: E.E. Lower has nothing to disclose. Conflict of interest: M. Mirsaeidi reports grants and personal fees from Mallinckrodt, outside the submitted work. Conflict of interest: L. O'Hare has nothing to disclose. Conflict of interest: M.J. Rumbak has nothing to disclose. Conflict of interest: L. Samavati has participated in a Questcor Advisory Board Meeting in 2014 and received $6500 compensation. Conflict of interest: R.P. Baughman reports grants and personal fees from Malllinckrodt, Novartis and Celgene, grants from Gilead, Genentech and Bayer, personal fees from West Pharmaceutical, during the conduct of the study., (Copyright ©ERS 2020.)

Pulmonary sarcoidosis presents substantial management challenges, with limited evidence on effective therapies and phenotypes. In the absence of definitive evidence, expert consensus can supply clinically useful guidance in medicine. An international panel of 26 experts participated in a Delphi process to identify consensus on pharmacological management in sarcoidosis with the development of preliminary recommendations.The modified Delphi process used three rounds. The first round focused on qualitative data collection with open-ended questions to ensure comprehensive inclusion of expert concepts. Rounds 2 and 3 applied quantitative assessments using an 11-point Likert scale to identify consensus.Key consensus points included glucocorticoids as initial therapy for most patients, with non-biologics (immunomodulators), usually methotrexate, considered in severe or extrapulmonary disease requiring prolonged treatment, or as a steroid-sparing intervention in cases with high risk of steroid toxicity. Biologic therapies might be considered as additive therapy if non-biologics are insufficiently effective or are not tolerated with initial biologic therapy, usually with a tumour necrosis factor-α inhibitor, typically infliximab.The Delphi methodology provided a platform to gain potentially valuable insight and interim guidance while awaiting evidenced-based contributions., Competing Interests: Conflict of interest: F.F. Rahaghi reports grants and consulting fees from Mallinckrodt, during the conduct of the study. Conflict of interest: R.P. Baughman reports grants and personal fees from Malllinckrodt, Novartis and Celgene, grants from Gilead, Genentech, Bayer and West Pharmaceutical, during the conduct of the study. Conflict of interest: L.A. Saketkoo has nothing to disclose. Conflict of interest: N.J. Sweiss has nothing to disclose. Conflict of interest: J.B. Barney has nothing to disclose. Conflict of interest: S.S. Birring has nothing to disclose. Conflict of interest: U. Costabel has nothing to disclose. Conflict of interest: E.D. Crouser has no relevant conflicts of interest to disclose. Conflict of interest: M. Drent has nothing to disclose. Conflict of interest: A.K. Gerke has nothing to disclose. Conflict of interest: J.C. Grutters has nothing to disclose. Conflict of interest: N.Y. Hamzeh has a patent pending from Prothena Inc. Conflict of interest: I. Huizar has no relevant conflicts of interest to disclose. Conflict of interest: W.E. James has nothing to disclose. Conflict of interest: S. Kalra has nothing to disclose. Conflict of interest: S. Kullberg has nothing to disclose. Conflict of interest: H. Li has nothing to disclose. Conflict of interest: E.E. Lower has nothing to disclose. Conflict of interest: L.A. Maier reports grants from National Institutes of Health: 1R01 HL127461-01A, 1R01HL11487-01A1, R01HL136681-01A1, 1R21 128738A-02, R21 HL140012-1, outside the submitted work. Conflict of interest: M. Mirsaeidi reports grants and personal fees from Mallinckrodt, outside the submitted work. Conflict of interest: J. Müller-Quernheim has nothing to disclose. Conflict of interest: E.M. Carmona Porquera reports other from ReSaph (Gilead), personal fees from American College of Chest Physicians (CHEST), outside the submitted work. Conflict of interest: L. Samavati participated in the Questcor Advisory Board Meeting 2014 and received $6500 compensation. Conflict of interest: D. Valeyre reports personal fees from Roche, Boehringer Ingelheim, AstraZeneca and Boehringer Ingelheim, outside the submitted work. Conflict of interest: M.B. Scholand reports other from Boehringer Ingelheim, Fibrogen, Global Blood Therapeutics and Genetech, outside the submitted work. In addition, M.B. Scholand has a patent Apparatus, Compositions and Methods for Assessment of Chronic Obstructive Pulmonary Disease Progression among Rapid and Slow Decline Conditions issued., (Copyright ©ERS 2020.)

Systemic sclerosis (SSc) is a progressive vasculopathic, fibrosing autoimmune condition, portending significant mortality; wherein interstitial lung disease (ILD) is the leading cause of death. Although lacking a definitive cure, therapeutics for (SSc-ILD) that stave progression exist with further promising primary and adjuvant compounds in development, as well as interventions to reduce symptom burden and increase quality of life. To date, there has been a significant but varied history related to systemic sclerosis-related interstitial lung disease trial design and endpoint designation. This is especially true of endpoints measuring patient-reported perceptions of efficacy and tolerability. This article describes the underpinnings and complexity of the science, methodology, and current state of patient-reported outcome measures used in (SSc-ILD) systemic sclerosis-related interstitial lung disease in clinical practice and trials., Competing Interests: Declaration of conflicting interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: The content is based solely on the unbiased research and expertise of the authors, they have received no financial incentives from any party to produce this publication. A.M.R., M.B.S. and M.R.L. report no conflicts of interest. A.M.R. and L.A.S. have provided consultation, research and education for Boehringer Ingelheim pharmaceuticals who are the sponsors for the edition of the Journal of Scleroderma and Related Disorders.

Background: Connective tissue growth factor (CTGF) is a secreted glycoprotein that has a central role in the process of fibrosis. This study was designed to assess the safety, tolerability, and efficacy of pamrevlumab (FG-3019), a fully recombinant human monoclonal antibody against CTGF, in idiopathic pulmonary fibrosis. The aim was to establish whether pamrevlumab could slow, stop, or reverse progression of idiopathic pulmonary fibrosis., Methods: The phase 2, randomised, double-blind, placebo-controlled PRAISE trial was done at 39 medical centres in seven countries (Australia, Bulgaria, Canada, India, New Zealand, South Africa, and the USA). Patients with idiopathic pulmonary fibrosis and percentage of predicted forced vital capacity (FVC) of 55% or greater were enrolled and randomly assigned (1:1) by use of interactive responsive technology to intravenous infusion of pamrevlumab 30 mg/kg or placebo every 3 weeks over 48 weeks (16 infusions). The primary efficacy outcome was change from baseline in percentage of predicted FVC at week 48. Disease progression (defined as a decline from baseline in percentage of predicted FVC of ≥10%, or death) at week 48 was a key secondary efficacy outcome. All patients in the pamrevlumab group received at least one dose of the study drug and were analysed for safety. Two patients in the placebo group were excluded from the intention-to-treat population for the efficacy analyses because of enrolment error. This trial is registered with ClinicalTrials.gov, NCT01890265., Findings: Between Aug 17, 2013, and July 21, 2017, 103 patients were randomly assigned (50 to pamrevlumab and 53 to placebo). Pamrevlumab reduced the decline in percentage of predicted FVC by 60·3% at week 48 (mean change from baseline -2·9% with pamrevlumab vs -7·2% with placebo; between-group difference 4·3% [95% CI 0·4-8·3]; p=0·033). The proportion of patients with disease progression was lower in the pamrevlumab group than in the placebo group at week 48 (10·0% vs 31·4%; p=0·013). Pamrevlumab was well tolerated, with a safety profile similar to that of placebo. Treatment-emergent serious adverse events were observed in 12 (24%) patients in the pamrevlumab group and eight (15%) in the placebo group, with three patients on pamrevlumab and seven on placebo discontinuing treatment. Of the three (6%) deaths in the pamrevlumab group and six (11%) in the placebo group, none was considered treatment related., Interpretation: Pamrevlumab attenuated progression of idiopathic pulmonary fibrosis and was well tolerated. Now in phase 3 development, pamrevlumab shows promise as a novel, safe, and effective treatment for idiopathic pulmonary fibrosis., Funding: FibroGen., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by irreversible loss of lung function and an unpredictable course of disease progression., Methods: The safety data for patients with IPF who received placebo in 6 clinical trials were pooled to examine the categories and frequencies of serious adverse events (SAEs) in this population., Results: In 1082 patients with IPF who received placebo, 673 SAEs were reported. Of these, 93 SAEs resulted in death (8.6% of patients). Respiratory-related conditions were the most frequently reported SAE (225 events, 16.33 per 100 patient-exposure years [PEY]), followed by infections and infestations (136 events, 9.87 per 100 PEY) and cardiac disorders (79 events, 5.73 per 100 PEY); these categories also had the most fatal outcomes (60, 10, and 10 deaths, respectively). The most frequently reported fatal respiratory-related SAEs were IPF and respiratory failure (38 and 11 patients, respectively), and the most frequently reported fatal infections and infestations and cardiac disorders were pneumonia (5 patients) and myocardial infarction (3 patients), respectively., Conclusions: This pooled analysis has value as a comparator for safety in future studies of IPF and provides insights in the natural evolution of both IPF and common comorbidities., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There are over 200 interstitial lung diseases (ILDs). In addition to patients with idiopathic pulmonary fibrosis (IPF), a percentage of patients with other ILDs also develop progressive fibrosis of the lung during their disease course. Patients with progressive-fibrosing ILDs may show limited response to immunomodulatory therapy, worsening symptoms and lung function and, ultimately, early mortality. There are few data for ILDs that may present a progressive fibrosing phenotype specifically, but we believe the burden and healthcare costs associated with these conditions may be comparable to those reported in IPF. This review discusses the burden of ILDs that may present a progressive fibrosing phenotype and the factors impacting healthcare utilisation., Competing Interests: Conflict of interest: C. Holtze reports non-financial support from Boehringer Ingelheim (writing assistance), during the conduct of the study. Conflict of interest: K. Flaherty reports personal fees from Boehringer Ingelheim (consultancy – IPF 2016), Genentech (consultancy – IPF 2015), Veracyte (consultancy – IPF 2017), Roche (consultancy – IPF 2017), France Foundation (IPF CME content and presentations), Fibrogen (consultancy – IPF 2016) and Sanofi-Genzyme (consultancy – IPF 2017), outside the submitted work. Conflict of interest: M. Kreuter reports grants and personal fees from Roche and Boehringer Ingelheim, during the conduct of the study. Conflict of interest: F. Luppi reports personal fees from Boehringer Ingelheim, grants and personal fees from Roche, during the conduct of the study. Conflict of interest: T. Moua has nothing to disclose. Conflict of interest: C. Vancheri reports grants and personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: M.B. Scholand reports other from Boehringer Ingelheim (advisory board and investigator in clinical trials), Genentech (advisory board and investigator in a clinical trial), Fibrogen (investigator in a clinical trial), and Global Blood Therapeutics (investigator in a clinical trial), outside the submitted work. In addition, M.B. Scholand has a patent “Apparatus, compositions and methods for assessment of chronic obstructive pulmonary disease progression among rapid and slow decline conditions” issued., (Copyright ©ERS 2018.)

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, and long-term oxygen therapy has been shown to reduce mortality in COPD patients with severe hypoxemia. However, the Long-term Oxygen Treatment Trial (LOTT), a large randomized trial, found no benefit of oxygen therapy in COPD patients with moderate hypoxemia. We hypothesized that there may be differences in response to oxygen which depend on genotype or gene expression. In a genome-wide time-to-event analysis of the primary outcome of death or hospitalization in 331 subjects, 97 single nucleotide polymorphisms (SNPs) showed evidence of interaction with oxygen therapy at P < 1e-5, including 7 SNPs near arylsulfatase B (ARSB; P = 6e-6). In microarray expression profiling on 51 whole blood samples from 37 individuals, at screening and/or at 12-month follow-up, ARSB expression was associated with the primary outcome depending on oxygen treatment. The significant SNPs were conditional expression quantitative trait loci for ARSB expression. In a network analysis of genes affected by long-term oxygen, two observed clusters including 26 co-expressed genes were enriched in mitochondrial function. Using data from the observational COPDGene Study, we validated the expression of 25 of these 26 genes, plus ARSB. The effect of long-term oxygen therapy in COPD varied based on ARSB expression and genotype. ARSB has previously been shown to be associated with hypoxemia in human bronchial and colonic epithelial cells and in a mouse model. In peripheral blood, long-term oxygen treatment affected expression of mitochondrial-related genes, a biologically relevant pathway in COPD. SNPs and expression of ARSB are associated with response to long-term oxygen in COPD. The ARSB SNPs were expression quantitative trait loci depending on oxygen therapy. Genes differentially expressed by long-term oxygen were enriched in mitochondrial functions. This suggests a potential biomarker to personalize use of long-term oxygen in COPD.

Background: Abnormal acid gastro-oesophageal reflux (GER) is hypothesised to play a role in progression of idiopathic pulmonary fibrosis (IPF). We aimed to determine whether treatment of abnormal acid GER with laparoscopic anti-reflux surgery reduces the rate of disease progression., Methods: The WRAP-IPF trial was a randomised controlled trial of laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER recruited from six academic centres in the USA. We enrolled patients with IPF, abnormal acid GER (DeMeester score of ≥14·7; measured by 24-h pH monitoring) and preserved forced vital capacity (FVC). We excluded patients with a FVC below 50% predicted, a FEV 1 /FVC ratio of less than 0·65, a history of acute respiratory illness in the past 12 weeks, a body-mass index greater than 35, and known severe pulmonary hypertension. Concomitant therapy with nintedanib and pirfenidone was allowed. The primary endpoint was change in FVC from randomisation to week 48, in the intention-to-treat population with mixed-effects models for repeated measures. This trial is registered with ClinicalTrials.gov, number NCT01982968., Findings: Between June 1, 2014, and Sept 30, 2016, we screened 72 patients and randomly assigned 58 patients to receive surgery (n=29) or no surgery (n=29). 27 patients in the surgery group and 20 patients in the no surgery group had an FVC measurement at 48 weeks (p=0·041). Intention-to-treat analysis adjusted for baseline anti-fibrotic use demonstrated the adjusted rate of change in FVC over 48 weeks was -0·05 L (95% CI -0·15 to 0·05) in the surgery group and -0·13 L (-0·23 to -0·02) in the non-surgery group (p=0·28). Acute exacerbation, respiratory-related hospitalisation, and death was less common in the surgery group without statistical significance. Dysphagia (eight [29%] of 28) and abdominal distention (four [14%] of 28) were the most common adverse events after surgery. There was one death in the surgery group and four deaths in the non-surgery group., Interpretation: Laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER is safe and well tolerated. A larger, well powered, randomised controlled study of anti-reflux surgery is needed in this population., Funding: US National Institutes of Health National Heart, Lung and Blood Institute., (Copyright © 2018 Elsevier Ltd. All rights reserved.)