@article{e10e18a9551b40d18baee966735e8a9e,
title = "Novel respiratory disability score predicts copd exacerbations and mortality in the spiromics cohort",
abstract = "Rationale: Some COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype. Objective: To define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death. Methods: We analyzed baseline data from a multi-center observational study (SPIROMICS). This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls). Measurements: We defined respiratory disability by ≥4 of 7 criteria: mMRC dyspnea scale ≥3; Veterans Specific Activity Questionnaire <5; 6-minute walking distance <250 m; St George{\textquoteright}s Respiratory Questionnaire activity domain >60; COPD Assessment Test >20; fatigue (FACIT-F Trial Outcome Index) <50; SF-12 < 20. Results: Using these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female). Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%. Compared with others, participants with disability had more emphysema (13.2 vs. 6.6%) and air-trapping (37.0 vs. 21.6%) on HRCT (P<0.0001). Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point −1.0 reliably identified disability. This disability score independently predicted future exacerbations ({\ss}=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001). Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability. Conclusion: Our novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruc-tion and certain inflammatory biomarkers. The disability score also proved to be an independent predictor of future exacerbations and death. These findings validate disability as an important phenotype in the spectrum of COPD.",
keywords = "Disability, Exacerbation rate, Frailty, Mortality, SPIROMICS",
author = "Cooper, {Christopher B.} and Robert Paine and Curtis, {Jeffrey L.} and Kanner, {Richard E.} and Martinez, {Carlos H.} and Meldrum, {Catherine A.} and Russell Bowler and Wanda O{\textquoteright}neal and Hoffman, {Eric A.} and David Couper and Miguel Quibrera and Gerald Criner and Dransfield, {Mark T.} and Han, {Meilan K.} and Hansel, {Nadia N.} and Krishnan, {Jerry A.} and Lazarus, {Stephen C.} and Peters, {Stephen P.} and Barr, {R. Graham} and Martinez, {Fernando J.} and Woodruff, {Prescott G.}",
note = "Funding Information: a founder and shareholder of VIDA Diagnostics, a company commercializing lung image analysis software developed, and reports personal fees from VIDA Diagnostics, during the conduct of the study. DC has grants from the NIH, reports grants from NHLBI, grants from COPD Foundation, during the conduct of the study and no other conflicts. MQ reports no conflicts. GC reports grants from Boehringer-Ingelheim, Novartis, Astra Zeneca, Respironics, MedImmune, Actelion, Forest, Pearl, Ikaria, Aeris, PneumRx, Pulmonx, personal fees from HE Health Care Solutions, Inc, Amirall, Boehringer-Ingelheim, Holaira. MTD reports receiving grants from the NIH, the Department of Defense, and the American Heart Association; consulting fees from Boehringer Ingelheim, GlaxoSmithKline, Novartis, Astra Zeneca, Yungjin, PneumRx/BTG, Pulmonx, Genentech, Boston Scientific, Quark Pharmaceuticals, Mereo and received grants from American Lung Association and NIH, and reports grants from NIH, during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from GlaxoSmithKline, personal fees from Boston Scientific, grants from American Lung Association, grants from Department of Defense, grants from Department of Veterans Affairs, personal fees from Mereo, personal fees from Quark, contracted clinical trial from Gala and Nuvaira, outside the submitted work. MKH has consulted for GSK, Boehringer Ingelheim and AstraZeneca, has received research support from Novartis and Sunovion and reports grants from NIH, NHLBI, and from COPD Foundation, during the conduct of the study; and Consulting for GSK, BI, Mylan, Merck and AstraZeneca, research support from Sunovion and Novartis. NNH reports grants and personal fees from AstraZeneca, GSK, Mylan, Boehringer Ingelheim, grants from NIH, COPD Foundation, outside the submitted work. JAK has received research grants from NIH and the Patient Centered Outcomes Research Institute. SCL reports grants from NIH/NHLBI, during the conduct of the study. SPP reports grants from MIH, HNLBI, during the conduct of the study. The authors report no other conflicts of interest in this work. RGB has grants from the NIH, Foundation for the NIH, COPD Foundation and Alpha-1 Foundation, and reports grants, personal fees from AstraZeneca, grants from Boehringer Ingelheim, grants from NIH, grants from COPD Foundation, personal fees from Mylan, outside the submitted work. FJM reports grants from NHLBI, National Institutes of Health, Publisher Copyright: {\textcopyright} 2020 Cooper et al.",
year = "2020",
doi = "10.2147/COPD.S250191",
language = "English (US)",
volume = "15",
pages = "1887--1898",
journal = "International Journal of COPD",
issn = "1176-9106",
publisher = "Dove Medical Press Ltd.",
}