{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:36:45Z","timestamp":1791095805823,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":283,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs Clinical Science Research and Development Service","doi-asserted-by":"publisher","award":["CX002193"],"award-info":[{"award-number":["CX002193"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Veterans Affairs Clinical Science Research and Development Service","award":["CX002193"],"award-info":[{"award-number":["CX002193"]}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The impact of respiratory exacerbation on chronic obstructive pulmonary disease (COPD) is well established. The effects of respiratory exacerbations in people with cigarette smoking but normal spirometry are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the association of respiratory exacerbations with lung function decline and mortality in people with normal spirometry and current or former cigarette smoking history.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed data from COPDGene study participants with \u2a7e10 pack-years of cigarette smoking and normal spirometry at enrollment (Visit 1) defined as post-bronchodilator FEV1\/FVC greater than or equal to the lower limit of normal and FEV1 greater than or equal to the lower limit of normal. We examined whether respiratory exacerbations occurring between Visit 1 and the 5-year follow-up visit (Visit 2) were associated with FEV1 decline and all-cause mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Among 2,939 participants with cigarette smoking history and normal lung function at Visit 1, each additional exacerbation between Visits 1 and 2 was associated with a 2.96 ml\/yr FEV1 decline (95% confidence interval [CI], 1.81 to 4.12; P\u2009&amp;lt;\u20090.001) at Visit 2. Experiencing one or more severe exacerbations between Visits 1 and 2 was associated with 14.6 ml\/yr FEV1 decline relative to those with no severe exacerbations (95% CI, 8.56 to 20.6; P\u2009&amp;lt;\u20090.001). Individuals with one or more severe exacerbations between Visits 1 and 2 had increased mortality compared with those with no severe exacerbations (17.1% vs. 9.8%; adjusted hazard ratio, 1.97; 95% CI, 1.40 to 2.77; P\u2009&amp;lt;\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Respiratory exacerbations in people with cigarette smoking but normal spirometry were associated with lung function decline. Experiencing a severe respiratory exacerbation was associated with increased mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202401-0023oc","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T13:57:11Z","timestamp":1739455031000},"page":"957-965","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":17,"title":["Respiratory Exacerbations and Lung Function Decline in People with Smoking History and Normal Spirometry"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-6740","authenticated-orcid":false,"given":"Spyridon","family":"Fortis","sequence":"first","affiliation":[{"name":"Center for Access & Delivery Research & Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, Iowa"},{"name":"Division of Pulmonary, Critical Care and Occupational Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Strand","sequence":"additional","affiliation":[{"name":"Division of Biostatistics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8418-4497","authenticated-orcid":false,"given":"Surya P.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ten Eyck","sequence":"additional","affiliation":[{"name":"Biostatistics and Research Design, Institute for Clinical and Translational Science, University of Iowa Hospitals and Clinics, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linder","family":"Wendt","sequence":"additional","affiliation":[{"name":"Biostatistics and Research Design, Institute for Clinical and Translational Science, University of Iowa Hospitals and Clinics, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trisha","family":"Parekh","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care, University of Texas at Austin Dell Medical School, Austin, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MeiLan K.","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Hokanson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, University of Colorado, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Kinney","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Colorado School of Public Health, Anschutz Medical Campus, University of Colorado, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-363X","authenticated-orcid":false,"given":"Russell P.","family":"Bowler","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4126-2467","authenticated-orcid":false,"given":"Emily S.","family":"Wan","sequence":"additional","affiliation":[{"name":"Veterans Affairs Boston Healthcare System, Jamaica Plain, Massachusetts"},{"name":"Channing Division of Network Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8644-2827","authenticated-orcid":false,"given":"Ken M.","family":"Kunisaki","sequence":"additional","affiliation":[{"name":"Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota; 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