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However, the implications of variable obstruction (VO), in which the prebronchodilator FEV1\/FVC ratio is less than 0.70 but increases to 0.70 or more after inhaled bronchodilators, have not been determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We explored differences in physiology, exacerbations, and health status in participants with VO compared with reference participants without obstruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort were obtained. Participants with VO were compared with reference participants without obstruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>We assessed differences in baseline radiographic emphysema and small airway disease at study entry, baseline, and change in lung function by spirometry, functional capacity by 6-minute walk, health status using standard questionnaires, exacerbation rates, and progression to COPD between the two groups. All models were adjusted for participant characteristics, asthma history, and tobacco exposure. We assessed 175 participants with VO and 603 reference participants without obstruction. Participants with VO had 6.2 times the hazard of future development of COPD controlling for other factors (95% confidence interval, 4.6\u20138.3; P\u2009&amp;lt;\u20090.001). Compared with reference participants, the VO group had significantly lower baseline pre- and post-bronchodilator (BD) FEV1, and greater decline over time in post-BD FEV1, and pre- and post-BD FVC. There were no significant differences in exacerbations between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Significant risk for future COPD development exists for those with pre- but not post-BD airflow obstruction. These findings support consideration of expanding spirometric criteria defining COPD to include pre-BD obstruction.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT 01969344).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202201-0094oc","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T13:15:32Z","timestamp":1652361332000},"page":"554-562","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":44,"title":["Reversible Airflow Obstruction Predicts Future Chronic Obstructive Pulmonary Disease Development in the SPIROMICS Cohort: An Observational Cohort Study"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6159-7435","authenticated-orcid":false,"given":"Russell G.","family":"Buhr","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, and"},{"name":"Center for the Study of Healthcare Innovation, Implementation, and Policy, Health Services Research and Development, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8096-0858","authenticated-orcid":false,"given":"Igor Z.","family":"Barjaktarevic","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Miguel","family":"Quibrera","sequence":"additional","affiliation":[{"name":"Collaborative Studies Coordinating Center, Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori A.","family":"Bateman","sequence":"additional","affiliation":[{"name":"Collaborative Studies Coordinating Center, Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4767-3494","authenticated-orcid":false,"given":"Eugene R.","family":"Bleecker","sequence":"additional","affiliation":[{"name":"Division of Genetics, Genomics, and Precision Medicine, University of Arizona, Tucson, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4313-9235","authenticated-orcid":false,"given":"David J.","family":"Couper","sequence":"additional","affiliation":[{"name":"Collaborative Studies Coordinating Center, Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5191-4847","authenticated-orcid":false,"given":"Jeffrey L.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan"},{"name":"Medical Service, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0405-608X","authenticated-orcid":false,"given":"Brett 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California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4511-4437","authenticated-orcid":false,"suffix":"III","given":"Robert","family":"Paine","sequence":"additional","affiliation":[{"name":"Division of Respiratory, Critical Care, and Occupational Medicine, University of Utah School of Medicine, Salt Lake City, Utah"},{"name":"Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, Utah; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7909-0253","authenticated-orcid":false,"given":"Stephen I.","family":"Rennard","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-4872","authenticated-orcid":false,"given":"Donald P.","family":"Tashkin","sequence":"additional","affiliation":[{"name":"Division 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