Pulmonary Rehabilitation in Idiopathic Pulmonary Fibrosis and COPD

Abstract

BackgroundThe adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison with COPD, remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program and to determine whether pulmonary rehabilitation is associated with survival in IPF.Research QuestionDo people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are noncompletion of or nonresponse to pulmonary rehabilitation, or both, associated with 1-year all-cause mortality in IPF?Study Design and MethodsUsing propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred for pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over 1 year after pulmonary rehabilitation discharge. Cox proportional hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality.ResultsSimilar pulmonary rehabilitation completion rates (IPF, 69%; COPD, 63%; P = .24) and improvements in exercise response were observed in both groups with no significant mean between-group differences in incremental shuttle walk test (ISWT) change (mean, 2 m [95% CI, –18 to 22 m]). Pulmonary rehabilitation noncompletion (hazard ratio [HR], 5.62 [95% CI, 2.24-14.08]) and nonresponse (HR, 3.91 [95% CI, 1.54-9.93]) were associated independently with increased 1-year all-cause mortality in IPF.InterpretationThis real-word study demonstrated that patients with IPF have similar completion rates and magnitude of response to pulmonary rehabilitation compared with a matched group of patients with COPD. In IPF, noncompletion of and nonresponse to pulmonary rehabilitation were associated with increased all-cause mortality. These data reinforce the benefits of pulmonary rehabilitation in patients with IPF. The adherence to and clinical efficacy of pulmonary rehabilitation in idiopathic pulmonary fibrosis (IPF), particularly in comparison with COPD, remains uncertain. The objectives of this real-world study were to compare the responses of patients with IPF with a matched group of patients with COPD undergoing the same supervised, outpatient pulmonary rehabilitation program and to determine whether pulmonary rehabilitation is associated with survival in IPF. Do people with IPF improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are noncompletion of or nonresponse to pulmonary rehabilitation, or both, associated with 1-year all-cause mortality in IPF? Using propensity score matching, 163 patients with IPF were matched 1:1 with a control group of 163 patients with COPD referred for pulmonary rehabilitation. We compared between-group pulmonary rehabilitation completion rates and response. Survival status in the IPF cohort was recorded over 1 year after pulmonary rehabilitation discharge. Cox proportional hazards regression explored the association between pulmonary rehabilitation status and all-cause mortality. Similar pulmonary rehabilitation completion rates (IPF, 69%; COPD, 63%; P = .24) and improvements in exercise response were observed in both groups with no significant mean between-group differences in incremental shuttle walk test (ISWT) change (mean, 2 m [95% CI, –18 to 22 m]). Pulmonary rehabilitation noncompletion (hazard ratio [HR], 5.62 [95% CI, 2.24-14.08]) and nonresponse (HR, 3.91 [95% CI, 1.54-9.93]) were associated independently with increased 1-year all-cause mortality in IPF. This real-word study demonstrated that patients with IPF have similar completion rates and magnitude of response to pulmonary rehabilitation compared with a matched group of patients with COPD. In IPF, noncompletion of and nonresponse to pulmonary rehabilitation were associated with increased all-cause mortality. These data reinforce the benefits of pulmonary rehabilitation in patients with IPF. Take-home PointsStudy Question: Do people with idiopathic pulmonary fibrosis (IPF) improve to the same extent with pulmonary rehabilitation as a matched group of individuals with COPD, and are noncompletion of or nonresponse to pulmonary rehabilitation, or both, associated with 1-year all-cause mortality in IPF?Results: This real-world study demonstrated that people with IPF show similar completion rates and response to pulmonary rehabilitation as matched individuals with COPD. In IPF, noncompletion and nonresponse to pulmonary rehabilitation were associated with increased all-cause mortality.Interpretation: This real-word study demonstrated that patients with IPF have similar completion rates and magnitude of response to pulmonary rehabilitation compared with a matched group of patients with COPD. In IPF, noncompletion of and nonresponse to pulmonary rehabilitation were associated with increased all-cause mortality. These data reinforce the benefits of pulmonary rehabilitation in patients with IPF.FOR EDITORIAL COMMENTS, SEE PAGES 597, AND 599 Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive decline in respiratory and physical function with a median survival of 3 to 5 years from diagnosis.1Fell C.D. Idiopathic pulmonary fibrosis: phenotypes and comorbidities.Clin Chest Med. 2012; 33: 51-57Google Scholar,2Holland A.E. Fiore J.F. Bell E.C. et al.Dyspnoea and comorbidity contribute to anxiety and depression in interstitial lung disease.Respirology. 2014; 19: 1215-1221Google Scholar Although pharmacologic therapies may slow lung function decline, their effect on symptom burden and quality of life are modest.3Noble P.W. Albera C. Bradford W.Z. et al.Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials.Lancet. 2011; 377: 1760-1769Google Scholar,4Richeldi L. du Bois R.M. Raghu G. et al.Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.N Engl J Med. 2014; 370: 2071-2082Google Scholar Pulmonary rehabilitation, a multidisciplinary individualized exercise and education program, originally developed for and validated in people with COPD, improves exercise capacity, dyspnea, and health-related quality of life in this population5McCarthy B. Casey D. Devane D. Murphy K. Murphy E. Lacasse Y. Pulmonary rehabilitation for chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2015; Google Scholar and has been postulated as having a role in the management of IPF. The supporting evidence for the benefits of pulmonary rehabilitation in IPF are more modest than in COPD. A Cochrane review that evaluated the efficacy of pulmonary rehabilitation in interstitial lung disease (ILD) (n = 182 with IPF allocated to intervention arm) concluded that although pulmonary rehabilitation was associated with improvement in people with IPF, the quality of evidence was low to moderate because of methodologic concerns.6Dowman L. Hill C.J. May A. Holland A.E. Pulmonary rehabilitation for interstitial lung disease.Cochrane Database Syst Rev. 2021; Google Scholar Furthermore, the magnitude of benefit from pulmonary rehabilitation in IPF, compared with COPD, is uncertain because of the more rapidly progressive nature of IPF and the greater prevalence of exercise-induced desaturation.6Dowman L. Hill C.J. May A. Holland A.E. Pulmonary rehabilitation for interstitial lung disease.Cochrane Database Syst Rev. 2021; Google Scholar Previous small studies comparing pulmonary rehabilitation response between IPF and COPD have shown a reduced magnitude of benefit in IPF.7Arizono S. Taniguchi H. Sakamoto K. et al.Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: comparison with chronic obstructive pulmonary disease.Sarcoidosis Vasc Diffuse Lung Dis. 2017; 34: 283-289Google Scholar,8Kozu R. Senjyu H. Jenkins S.C. Mukae H. Sakamoto N. Kohno S. Differences in response to pulmonary rehabilitation in idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.Respiration. 2011; 81: 196-205Google Scholar Recent data also have shown an association between pulmonary rehabilitation completion and response with survival in COPD.9Lindenauer P.K. Stefan M.S. Pekow P.S. et al.Association between initiation of pulmonary rehabilitation after hospitalization for COPD and 1-year survival among Medicare beneficiaries.JAMA. 2020; 323: 1813-1823Google Scholar, 10Houchen-Wolloff L. Williams J.E. Green R.H. et al.Survival following pulmonary rehabilitation in patients with COPD: the effect of program completion and change in incremental shuttle walking test distance.Int J Chron Obstruct Pulmon Dis. 2018; 13: 37Google Scholar, 11Camillo C.A. Langer D. Osadnik C.R. et al.Survival after pulmonary rehabilitation in patients with COPD: impact of functional exercise capacity and its changes.Int J Chron Obstruct Pulmon Dis. 2016; 11: 2671Google Scholar However, limited survival data exist in people with IPF. In a recent Cochrane systematic review of pulmonary rehabilitation for ILD, the authors identified only three trials in people with IPF (n = 127 participants, with 67 receiving pulmonary rehabilitation) that reported on survival.6Dowman L. Hill C.J. May A. Holland A.E. Pulmonary rehabilitation for interstitial lung disease.Cochrane Database Syst Rev. 2021; Google Scholar Although a trend toward reduced mortality with pulmonary rehabilitation was found, only a small number of deaths were observed (three with pulmonary rehabilitation intervention, and eight with control treatment). Given the limited evidence base, clinical guidelines have provided conflicting recommendations. Although the United Kingdom National Institute for Health and Care Excellence (which largely bases its recommendations on cost-effectiveness) recommends regular assessment for and offering pulmonary rehabilitation to people with IPF,12National Institute for Health and Care ExcellenceIdiopathic pulmonary fibrosis: the diagnosis and management of suspected idiopathic pulmonary fibrosis. 2013. National Institute for Health and Care Excellence website.https://www.nice.org.uk/guidance/cg163/chapter/introductionDate accessed: January 10, 2019Google Scholar the joint American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association guidelines on the diagnosis and treatment of IPF published in 2011 made a weak recommendation for pulmonary rehabilitation in IPF,13Raghu G. Collard H.R. Egan J.J. et al.An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management.Am J Respir Crit Care Med. 2011; 183: 788-824Google Scholar and the updated guidelines did not discuss the role of pulmonary rehabilitation.14Raghu G. Rochwerg B. Zhang Y. et al.An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline.Am J Respir Crit Care Med. 2015; 192: e3-e19Google Scholar The British Thoracic Society Guidelines15Bolton C.E. Bevan-Smith E.F. Blakey J.D. et al.British Thoracic Society guideline on pulmonary rehabilitation in adults: accredited by NICE.Thorax. 2013; 68: ii1-ii30Google Scholar and the Australia and New Zealand Guidelines16Alison J.A. McKeough Z.J. Johnston K. et al.Australian and New Zealand Pulmonary Rehabilitation Guidelines.Respirology. 2017; 22: 800-819Google Scholar for pulmonary rehabilitation provide weak recommendation for the provision of pulmonary rehabilitation in individuals with ILD with the recognition that benefits are unlikely to be sustained15Bolton C.E. Bevan-Smith E.F. Blakey J.D. et al.British Thoracic Society guideline on pulmonary rehabilitation in adults: accredited by NICE.Thorax. 2013; 68: ii1-ii30Google Scholar and that the quality of evidence is low.16Alison J.A. McKeough Z.J. Johnston K. et al.Australian and New Zealand Pulmonary Rehabilitation Guidelines.Respirology. 2017; 22: 800-819Google Scholar Similarly, the American Thoracic Society and European Respiratory Society Statement on pulmonary rehabilitation did not make a recommendation for pulmonary rehabilitation in IPF.17Spruit M.A. Singh S.J. Garvey C. et al.An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation.Am J Respir Crit Care Med. 2013; 188: e13-e64Google Scholar Given the uncertainty over the role of pulmonary rehabilitation in IPF management, the overall study aims were to provide real-world data on the effects of pulmonary rehabilitation in patients with IPF compared with those with COPD, a population in whom the benefit and magnitude of improvement with pulmonary rehabilitation are well established, and to understand the magnitude of those effects and their clinical consequences. Specifically, the primary objective was to compare the responses of people with IPF with a matched group of people with COPD undergoing the same supervised outpatient pulmonary rehabilitation program. A secondary objective was to determine whether completion of or response to pulmonary rehabilitation, or both, are associated with survival in people with IPF. We hypothesized that people with IPF would show a blunted response to pulmonary rehabilitation with reduced completion rates compared with matched people with COPD. We also hypothesized that noncompletion or nonresponse to pulmonary rehabilitation would be associated with increased mortality in IPF. We prospectively recruited patients with IPF consecutively referred to the Harefield Pulmonary Rehabilitation Unit between June 2013 and July 2018. Inclusion criteria were a primary diagnosis of IPF determined by a specialist ILD multidisciplinary team according to international guidelines14Raghu G. Rochwerg B. Zhang Y. et al.An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline.Am J Respir Crit Care Med. 2015; 192: e3-e19Google Scholar and referral to pulmonary rehabilitation in line with national guidelines.18British Thoracic Society. Quality standards for pulmonary rehabilitation in adults. Br Thorac Soc Rep. 2014;6(2). https://www.brit-thoracic.org.uk/quality-improvement/quality-standards/pulmonary-rehabilitation/. Accessed May 15, 2020.Google Scholar Exclusion criteria included a coexisting diagnosis of COPD. Patients provided informed consent and the study was approved by the London Riverside and London Central Research Ethics Committee. Because national clinical guidance in the United Kingdom recommends the offer of pulmonary rehabilitation to people with IPF,12National Institute for Health and Care ExcellenceIdiopathic pulmonary fibrosis: the diagnosis and management of suspected idiopathic pulmonary fibrosis. 2013. National Institute for Health and Care Excellence website.https://www.nice.org.uk/guidance/cg163/chapter/introductionDate accessed: January 10, 2019Google Scholar it was not considered ethical to a control group of patients with IPF the of referral to pulmonary rehabilitation. The control group patients with COPD, according to international D. A. A. et for the management, and of chronic obstructive lung the Respir Scholar and referred over the same An for this group was a diagnosis of coexisting IPF. was by propensity score S. et al.Pulmonary rehabilitation in a Respir Scholar the a control group matched that the propensity Scholar 1:1 for Research Respiratory score and incremental shuttle walk test (ISWT) between the groups was mean An to propensity score for the effects of in 2011; Scholar both those with to exercise and that would exercise were included J.E. R. Lung and Respir Scholar R. R. P.W. J.A. of the Research as a of in patients with chronic obstructive pulmonary Scholar et and of the incremental shuttle walk in idiopathic pulmonary fibrosis: a 2018; Scholar A of quality of life for clinical trials in chronic lung Scholar and for status et associated with slow in idiopathic pulmonary 2018; on physical for of in clinical 2018. 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We demonstrated that a real-world pulmonary rehabilitation program is associated with significant improvements in exercise capacity, dyspnea, and health-related quality of life in IPF. These as well as completion were with those observed in a propensity group of patients with COPD. with pulmonary rehabilitation noncompletion of or nonresponse to pulmonary rehabilitation were associated independently with all-cause mortality 1 year in IPF. These data provide evidence to the provision of pulmonary rehabilitation in IPF. only small of patients with IPF have been recruited to trials of pulmonary rehabilitation or exercise allocated to intervention L. Hill C.J. May A. Holland A.E. Pulmonary rehabilitation for interstitial lung disease.Cochrane Database Syst Rev. 2021; Google Scholar remains the benefits of pulmonary rehabilitation in IPF because of methodologic of small to and program than international L. Hill C.J. May A. Holland A.E. Pulmonary rehabilitation for interstitial lung disease.Cochrane Database Syst Rev. 2021; Google Scholar study to the by real-world data of patients with IPF undergoing pulmonary rehabilitation. Although are for people with COPD, study demonstrated that people with IPF similar clinical benefits and completion rates to those with COPD. a trend for completion rates in the IPF compared with the COPD group was that may be by not included in the propensity a number of in the in the IPF studies have compared the magnitude of change associated with pulmonary rehabilitation in IPF and S. Taniguchi H. Sakamoto K. et al.Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: comparison with chronic obstructive pulmonary disease.Sarcoidosis Vasc Diffuse Lung Dis. 2017; 34: 283-289Google Scholar,8Kozu R. Senjyu H. Jenkins S.C. Mukae H. Sakamoto N. Kohno S. Differences in response to pulmonary rehabilitation in idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.Respiration. 2011; 81: 196-205Google Scholar An study of 22 patients with IPF and a control group of patients with COPD reported similar effect for functional exercise capacity (IPF, COPD, after a S. Taniguchi H. Sakamoto K. et al.Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis: comparison with chronic obstructive pulmonary disease.Sarcoidosis Vasc Diffuse Lung Dis. 2017; 34: 283-289Google Scholar in exercise capacity, dyspnea, and quality of life in IPF. The are to to years of or were small disease and no of between-group et R. Senjyu H. Jenkins S.C. Mukae H. Sakamoto N. Kohno S. 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