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. 2024 Sep 27;11(5):444-459.
doi: 10.15326/jcopdf.2023.0490.

Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study

Jeffrey L Curtis  1   2   3 , Lori A Bateman  4 , Susan Murray  5 , David J Couper  4 , Wassim W Labaki  1 , Christine M Freeman  1   3   6 , Kelly B Arnold  7 , Stephanie A Christenson  8 , Neil E Alexis  9 , Mehmet Kesimer  10 , Richard C Boucher  10 , Robert J Kaner  11 , Igor Barjaktarevic  12 , Christopher B Cooper  12 , Eric A Hoffman  13 , R Graham Barr  14 , Eugene R Bleecker  15 , Russell P Bowler  16 , Alejandro Comellas  17 , Mark T Dransfield  18 , Michael B Freedman  19 , Nadia N Hansel  20 , Jerry A Krishnan  19 , Nathaniel Marchetti  21 , Deborah A Meyers  16 , Jill Ohar  22 , Wanda K O'Neal  10 , Victor E Ortega  15 , Robert Paine Iii  23 , Stephen P Peters  22 , Benjamin M Smith  14 , Jadwiga A Wedzicha  24 , J Michael Wells  17 , Prescott G Woodruff  8 , MeiLan K Han  1 , Fernando J Martinez  11
Affiliations

Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study

Jeffrey L Curtis et al. Chronic Obstr Pulm Dis. .

Abstract

Background: The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition.

Objectives: Accordingly, with National Heart, Lung and Blood Institute support, we initiated the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression.

Methods/discussion: SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global initiative for chronic Obstructive Lung Disease (GOLD) groups 0-2 or with preserved ratio-impaired spirometry; and an additional n=40 never-smoker controls. Participants undergo baseline and 3-year follow-up visits, each including high-resolution computed tomography, respiratory oscillometry and spirometry (pre- and postbronchodilator administration), exhaled breath condensate (baseline only), and extensive biospecimen collection, including sputum induction. Symptoms, interim health care utilization, and exacerbations are captured every 6 months via follow-up phone calls. An embedded bronchoscopy substudy involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture.

Conclusion: SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

Keywords: SPIROMICS; health-related quality of life; imaging phenotypes; preserved ratio-impaired spirometry; smoking-related lung disease.

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Conflict of interest statement

JLC reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NHLBI, NIAID, Department of Veterans Affairs, Department of Defense; consulting fees from CSL Behring, LLC; speaking fees from AstraZeneca; and data safety monitoring board (DSMB) participation for Novartis; all outside this project. LAB reports funding of this project from NIH/NHLBI and the COPD Foundation; speaking fees from Konica Minolta and Continuing Education Alliance, outside this project. SM reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NIH, outside this project. DJC reports funding of this project from NHLBI and the COPD Foundation. WWL reports funding for participation in this project from K23HL151751 from NHLBI; and personal fees from the Continuing Education Alliance, outside this project. CMF reports funding of this project from NIH/NHLBI and the COPD Foundation; grant support from the Department of Veterans Affairs, and uncompensated service as a board member of the Veterans Education and Research Association of Michigan, outside this project. KBA reports funding for participation in this project from R01HL144849 from NHLBI. SAC reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NHLBI, American Lung Association; consulting fees from Amgen, AstraZeneca, GSK, Glenmark Pharmaceuticals, and Sanofi/Regeneron; speaking fees from MJH Holdings LLC (Physicians’ Educational Resource, Sanofi/Regeneron, Sunovion, UpToDate, and Wolters Kluwer Health); travel support from AstraZeneca and GSK; DSMB participation for AstraZeneca, GSK, and Sanofi/Regeneron; and an uncompensated board membership for the American Thoracic Company, all outside this project. NEA reports funding of this project from NHLBI and the COPD Foundation. RCB reports grants from NHLBI, NIDDK, the Cystic Fibrosis Foundation, Emergent Ventures, and UNC-Chapel Hill; and royalties, consulting fees, and stock options from Parion Sciences Enterprise Therapeutics, for which he is Board Chairman, all outside this project. RJK reports grants from NHLBI, Boehringer Ingelheim, Bellerophon, CLS Behring, Genentech, Respirvant, Toray and the Department of Defense; royalties from UpToDate; consulting fees from AstraZeneca and Galapagos; speaking fees from Boehringer Ingelheim, the France Foundation, Genentech, and Vindico; DSMB participation for Boehringer Ingelheim, Genetech, Pliant, and PureTech; uncompensated participation in the board of the Pulmonary Wellness Foundation; stock options, for which he paid, in Air Cycle Systems and Doximity; and medical writing fees from AstraZeneca, Boehringer Ingelheim, Galapagos, and Genentech, all outside this project. IB reports grants from Theravance and Viatris and Aerogen; consulting fees from AstraZeneca, Grifols, Inhibrx, Sanofi, Takeda, Theravance and Viatris, and Verona Pharma; speaking fees from Grifols; and membership on the American Thoracic Society Pulmonary Function Committee and the COPD Foundation Nebulizer Consortium, all outside this project. CBC reports funding of this project from NIH/NHLBI and the COPD Foundation; royalties from Cambridge University Press; personal consulting fees from MGC Diagnostics, Chiesi, Herbalide Nutrition Institute, Respiree, and Aer Therapeutics; speaking fees from GlaxoSmithKline and Chulalongkorn University; payment from various law firms; travel fees from MGC Diagnostics; and personal fees for DSMB participation from NUVAIRA and Horizon Therapeutics, all outside this project. EAH reports funding of this project from NIH/NHLBI and the COPD Foundation; and stock options from VIDA Diagnostics, which he founded, outside this project. RGB reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NIH/NHLBI and the American Lung Association; and membership on the COPD Foundation Medical and Scientific Advisory Committee, outside this project. ERB reports grants from AstraZeneca, Genzyme, Novartis, Regeneron, and Sanofi/Genzyme; consulting fees from AstraZeneca, GSK, Knopp Pharmaceuticals, Novartis, Regeneron, and Sanofi/Genzyme; speaking fees from AstraZeneca; travel support from AstraZeneca, GSK, Novartis, Regeneron, and Sanofi/Genzyme, outside this project. RPB reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NIH; royalties from Abcam; consulting fees from GNS Health Care, Theravance, and GSK, outside this project. AC reports funding of this project from NIH/NHLBI and the COPD Foundation; grant funding from National Center for Advancing Translational Sciences and the National Institute of Environmental Health Sciences, outside this project; personal consulting fees from GSK, AstraZeneca, Elli Lilly; and nonpaid consultancy from VIDA, outside this project. MTD reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from the American Lung Association and the Department of Defense; Royalties from UpToDate; consulting fees from AstraZeneca, GSK, Novartis, Pulmonx, and Teva; all outside this project. NNH reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NIH, the COPD Foundation, AstraZeneca, and GSK; DSMB participation for AstraZeneca and GSK, outside this project. JAK reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NHLBI, the COPD Foundation, American Lung Association, Regeneron, Sergey Brin Family Foundation, and Patient-Centered Outcomes Research Institute; consulting fees from AstraZeneca, BData, Inc., CereVu Medical, GSK and Propeller/ResMed; speakers fees from the American Academy of Asthma, Allergy & Immunology, and the University of Chicago; travel support from the American Thoracic Society and the Global Initiative for Asthma; board membership for the COPD Foundation Medical and Scientific Advisory Committee, the Global Initiative for Asthma, and the Respiratory Health Association, all outside this project. NM reports funding of this project from NIH/NHLBI and the COPD Foundation. DAM reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from GSK; consulting fees from AstraZeneca, outside this project. JO reports a small business grant from NIH; grants from Boehringer-Ingelheim, Sunovion Pharmaceutical, TEVA, Moore Foundation; consulting fees from AstraZeneca, Boehringer-Ingelheim, and Verona; expert testimony fees from Coffey Law, Fox Rothchild, Frankline Casualty, Wallace & Graham, Simmons Hanley, Reid Acree and Kazan Law, all outside this project. WKO reports funding of this project from NHLBI and the COPD Foundation. VEO reports grants from NHLBI; and DSMB submission for Sanofi/Regeneron, outside this project. RP reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from Department of Veterans Affairs; consulting fees from Partner Therapeutics, outside this project. SPP reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NHLBI; royalties from UpToDate; consulting fees from PPD and Syneos; DSMB participation for GSK and Novartis; all outside this project. JAW reports grants from 37Clnical, AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, GSK and Novartis; consulting fees from AstraZeneca, Epiendo, Gilead, GSK, Novartis, Pieris, Pulmatrix; speakers fees from AstraZeneca, Boehringer Ingelheim, Novartis, and Recipharm; DSMB participation in Virtus; and board membership on Will March 2022 and the American Thoracic Society, all outside this project. JMW reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NHBLI, Department of Veterans Affairs, ARCUS-Med, Grifols, Mereo BioPharma, Medscape, and Verona; speaking fees from Medscape; DSMB participation for AstraZeneca, Boehringer-Ingelheim, GSK, and Takeda; stock options from Alveolus Bio; and support for medical writing from GSK and Takeda, all outside this project. PGW reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NHLBI and Genentech; consulting fees from Amgen, AstraZeneca, Sanofi, and Roche; and speaking honoraria from Hamilton University, Northwestern University and Vanderbilt University, all outside this project. MKH reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from NHLBI, the American Lung Association, AstraZeneca, Boehringer Ingelheim, Biodesix, COPD Foundation, Gala Therapeutics, Novartis, Nuvaira, and Sunovion; royalties from Norton Publishing, Penguin Random House, and UpToDate; consulting fees from Amgen, AstraZeneca, Altesa BioPharma, Aerogen, Boehringer Ingelheim, Devpro, Merck, Mylan, Novartis, Polarian, Pulmonx, Regeneron, Sanofi, Teva, United Therapeutics, and Verona; speaking fees from AstraZeneca, Boehringer Ingelheim, Cipla, Chiesi, GSK, Integrity;DSMB participation for Medtronic and Novartis; board membership for the American Lung Association, the COPD Foundation, American Thoracic Society (journal editor), Emerson School Board, GOLD scientific committee; stock options for Altesa BioPharma and Meissa Vaccines; medical writing for AstraZeneca, Boehringer Ingelheim, GSK and Novartis; and personal fees from Integrity and Medscape; all outside this project. FJM reports funding of this project from NIH/NHLBI and the COPD Foundation; grants from AstraZeneca, Chiesi, GSK and Sanofi/Regeneron; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Novartis, Polaran, Sanofi/Regeneron, Sunovion, Teva, Theravance/Viatris, and UpToDate; speaking fees from AstraZeneca and GSK; DSMB participation for GSK and Medtronic; and remuneration from the American Thoracic Society, all outside this project. MBF and MK report no conflicts.

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