Respiratory exacerbations are associated with muscle loss in current and former smokers.

Muscle wasting is a recognised extra-pulmonary complication in chronic obstructive pulmonary disease and has been associated with increased risk of death. Acute respiratory exacerbations are associated with reduction of muscle function, but there is a paucity of data on their long-term effect. This study explores the relationship between acute respiratory exacerbations and long-term muscle loss using serial measurements of CT derived pectoralis muscle area (PMA). Participants were included from two prospective, longitudinal, observational, multicentre cohorts of ever-smokers with at least 10 pack-year history. The primary analysis included 1332 (of 2501) participants from Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and 4384 (of 10 198) participants from Genetic Epidemiology of COPD (COPDGene) who had complete data from their baseline and follow-up visits. PMA was measured on chest CT scans at two timepoints. Self-reported exacerbation data were collected from participants in both studies through the use of periodic longitudinal surveys. Age-related and excess muscle loss over time. Age, sex, race and body mass index were associated with baseline PMA. Participants experienced age-related decline at the upper end of reported normal ranges. In ECLIPSE, the exacerbation rate over time was associated with an excess muscle area loss of 1.3% (95% CI 0.6 to 1.9, p<0.001) over 3 years and in COPDGene with an excess muscle area loss of 2.1% (95% CI 1.2 to 2.8, p<0.001) over 5 years. Excess muscle area decline was absent in 273 individuals who participated in pulmonary rehabilitation. Exacerbations are associated with accelerated skeletal muscle loss. Each annual exacerbation was associated with the equivalent of 6 months of age-expected decline in muscle mass. Ameliorating exacerbation-associated muscle loss represents an important therapeutic target.

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Competing interests: MTD reports grant funding from the National Institutes of Health relevant to the submitted work. Outside the submitted work, he reports grants from the American Lung Association, Department of Veterans Affairs, and the Department of Defense. He reports consulting fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, PneumRx, Quark Pharmaceuticals and Mereo. He is involved in contracted clinical trials with Boehringer Ingelheim, GlaxoSmithKline, Novartis, AstraZeneca, Yungjin, PneumRx, Pulmonx, Boston Scientific, Gala and Nuvaira. RC reports grant funding from the National Institutes of Health relevant to the submitted work. Outside the submitted work, he reports consulting fees or advisory board membership from Boehringer Ingelheim, GlaxoSmithKline, Astra Zeneca, Abbott, Genentech and Regeneron. He is involved in contracted clinical trials with Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Genentech and Regeneron. HR reports grant funding from the National Institutes of Health and the Tobacco Related Disease Research Program relevant to the submitted work. Outside the submitted work, he is involved in contracted clinical trials with Boehringer Ingelheim, GlaxoSmithKline, Novartis, AstraZeneca, Astellas, Genentech and Regeneron. WWL reports funding from the National Institutes of Health, non-financial support from Pulmonx, and personal fees from Konica Minolta, outside of the submitted work. MKH reports grant funding from the National Institutes of Health relevant to the submitted work. Outside the submitted work she reports grant funding from Verona, Mylan and Merck. She reports personal fees from GlaxoSmithKline, AstraZeneca and Boehringer Ingelheim. She reports other support from Novartis and Suovion. KAY and MS report grant funding from the National Institutes of Health relevant to the submitted work. RaulSJE reports funding from the National Institutes of Health relevant to the submitted work. Outside the submitted work, he reports grants from Boehringer Ingelheim and personal fees from Leuko labs and Chiesi. He is also a founder and co-owner of Quantitative Imaging Solutions which is a company that provides image based consulting and develops software to enable data sharing. BJM reports grants from AstraZeneca, GlaxoSmithKline, Sunovion, Pearl Research and the National Heart Lung Blood Institute. He reports trial related activity from AzatraZeneca, Spiration, GlaxoSmithKline, Sunovision, Third Pole and Takeda. He reports CME related support from Mt Sinai, WebMD, National Jewish Health, American College of Chest Physicians, Projects in Knowledge, Hybrid Communications, Medscape, Ultimate Medical Academy, Eastern Pulmonary Society, Catamount Medical, Eastern Va Medical Center, Academy Continued Health Learning and Wolters Kluwer Health, from outside the submitted work. He is involved with the medical advisory board for Verona, Boehringer Ingelheim, Theravance, Circassia, Phillips, Science 24/7, AstraZeneca and GlaxoSmithKline. All activities are outside of the submitted work. GRW reports grants from the National Institutes of Health, Boehringer Ingelheim, BTG Interventional Medicine, and Janssen Pharmaceuticals. He reports consulting work for Boehringer Ingelheim, PulmonX, Janssen Pharmaceuticals, GlaxoSmithKline, Novartis, Vertex and CSL Behring. He reports advisory board involvement with Boehringer Ingelheim, Vertex and CSL Behring. He is also a founder and co-owner of Quantitative Imaging Solutions which is a company that provides image based consulting and develops software to enable data sharing. All activities are outside the submitted work.