TY - JOUR T1 - Challenging the obesity paradox: extreme obesity and COPD mortality in the SUMMIT Trial JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00902-2020 SP - 00902-2020 AU - Emily P. Brigham AU - Julie A. Anderson AU - Robert D. Brook AU - Peter M. A. Calverley AU - Bartolome R. Celli AU - Nicholas J. Cowans AU - Courtney Crim AU - James E. Diserens AU - Fernando J. Martinez AU - Meredith C. McCormack AU - David E. Newby AU - Julie Yates AU - Jorgen Vestbo AU - Tianshi David Wu AU - Robert A. Wise Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2021/05/06/23120541.00902-2020.abstract N2 - Populations with COPD demonstrate higher survival in overweight and obese compared with normal weight; the “obesity paradox.” Relationships in less severe COPD are unclear, as is the impact of cardiovascular risk, and few studies include individuals at extremes of obesity.We examined the relationship between body mass index (BMI, defined as underweight: <20 kg·m−2, normal: 20–25 kg·m−2, overweight: 25-<30 kg·m−2, obese class I: 30-<35 kg·m−2, class II: 35-<40 kg·m−2, class III: ≥40 kg·m−2), morbidity, and mortality in the SUMMIT trial population (n=16 485), characterised by moderate COPD and heightened cardiovascular risk with a substantial proportion with class III obesity. The association between BMI category and time to event was modeled via proportional hazards (reference normal weight) adjusted for demographics and cardiorespiratory disease.Consistent with the paradox, underweight individuals demonstrated higher mortality (HR 1.31 (95%CI 1.04–1.64)), with lower mortality among overweight (HR 0.62 (95%CI 0.52–0.73)) and obese class I (HR 0.75 (95%CI 0.62–0.90)). However, mortality increased in obese class III (HR 1.36 (95%CI 1.00–1.86)). Death was primarily attributable to cardiovascular causes.Within a large, multinational cohort with moderate COPD and increased cardiovascular risk, the phenomenon of reduced mortality with obesity did not persist at BMI>40 kg·m−2, suggesting that obesity may not remain protective at the extremes in this population.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. Brigham has nothing to disclose.Conflict of interest: Dr. Anderson reports and JA is an employee of and owns shares in GSK.Conflict of interest: R.D. Brook reports personal fees from GSK for a steering committee during the conduct of the study.Conflict of interest: P.M.A. Calverley reports that he was was a member of the SUMMIT Science Committee supported by GSK; and he was paid for the conduct of the SUMMIT study by GSK, was paid for speaking at a company meeting and for advice on study design by AstraZeneca, he advised on development of new trials and has spoken for Boehringer Ingelheim at sponsored meetings, and he has received personal fees for speaking at sponsored meeting from Novartis, outside the submitted work.Conflict of interest: Dr. Celli reports personal fees from Glaxo Smith Kline, during the conduct of the study; personal fees from Astra Zeneca, personal fees from Sanofi Aventis, personal fees from Chiesi, personal fees from Novartis, personal fees from Menarini, personal fees from Pumonx, outside the submitted work; .Conflict of interest: N.J. Cowans reports this study was funded by GlaxoSmithKline Plc; and he is an employee of Veramed Ltd, a contract research organisation undertaking contracted statistical analyses of respiratory studies funded by GlaxoSmithKline Plc.Conflict of interest: C. Crim is an employee of GSK and holds GSK stocks/shares; this study was funded by GSK (NCT01313676, GSK study number 113782; Study to Understand Mortality and Morbidity In COPD Trial (SUMMIT)).Conflict of interest: J.E. Diserens reports this study was funded by GlaxoSmithKline Plc; and he is an employee of Veramed Ltd, a contract research organisation undertaking contracted statistical analyses of respiratory studies funded by GlaxoSmithKline Plc.Conflict of interest: Dr. Martinez reports grants from NHLBI, during the conduct of the study; grants from National Institutes of Health, personal fees from Continuing Education, personal fees from Forest Laboratories, other from Janssen, personal fees from GlaxoSmithKline, personal fees from Nycomed/Takeda, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Bellerophon (formerly Ikaria), personal fees from Genentech, personal fees from Novartis, personal fees from Pearl, personal fees from Roche, personal fees from Sunovion, personal fees from Theravance, personal fees from CME Incite, personal fees from Annenberg Center for Health Sciences at Eisenhower, personal fees from Integritas, personal fees from InThought, personal fees from National Association for Continuing Education, personal fees from Paradigm Medical Communications, LLC, personal fees from PeerVoice, personal fees from UpToDate, personal fees from Haymarket Communications, personal fees from Western Society of Allergy and Immunology, from Proterixbio (formerly Bioscale), personal fees from Unity Biotechnology, personal fees from ConCert Pharmaceuticals, personal fees from Lucid, personal fees from Methodist Hospital, personal fees from Columbia University, personal fees from Prime Healthcare Ltd, personal fees from WebMD, personal fees from PeerView Network, personal fees from California Society of Allergy and Immunology, personal fees from Chiesi, personal fees from Puerto Rico Thoracic Society, outside the submitted work.Conflict of interest: Dr. McCormack reports other from UptoDate, outside the submitted work; .Conflict of interest: Dr. Newby reports grants and personal fees from GSK, during the conduct of the study.Conflict of interest: Dr. Yates reports and JCY is an employee of and owns shares in GSK..Conflict of interest: J. Vestbo was partly reimbursed for his work as Chair of the SUMMIT Steering Committee buy GlaxoSmithKline during the conduct of the study; and reports consultancy for COPD phase 2 and 3 programmes and payment for lectures including service in speaker bureaus from GlaxoSmithKline, Chiesi Pharmaceuticals, Boehringer Ingelheim, Novartis and AstraZeneca, outside the submitted work.Conflict of interest: Dr. Wu has nothing to disclose.Conflict of interest: Professor Wise reports grants and personal fees from GlaxoSmithKline, during the conduct of the study; grants and personal fees from AstraZeneca/Medimmune, grants and personal fees from Boehringer Ingelheim, personal fees from Contrafect, personal fees from Pulmonx, personal fees from Roche/Genentech, personal fees from Spiration, personal fees from Sunovion, grants from Pearl Therapeutics, personal fees from Merck, personal fees from Circassia, personal fees from Pneuma, personal fees from Verona, personal fees from Bonti, personal fees from Denali, personal fees from Aradigm, personal fees from Mylan, personal fees from Theravance, personal fees from Propeller Health, personal fees from Kiniksa, personal fees from Syneos, outside the submitted work. 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