{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:00:51Z","timestamp":1793829651987,"version":"4.6.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Department of Respiratory Medicine and the Copenhagen General Population Study, Copenhagen University Hospital \u2013 Herlev and Gentofte","id":[{"id":"https:\/\/ror.org\/05bpbnx46","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Department of Respiratory Medicine and the Copenhagen General Population Study, Copenhagen University Hospital \u2013 Herlev and Gentofte","id":[{"id":"https:\/\/ror.org\/05bpbnx46","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Randomized controlled trials only include a subset of patients with chronic obstructive pulmonary disease (COPD) fulfilling strict inclusion criteria. Thus, most patients with COPD in a real-world setting do not have the necessary evidence to support treatment effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To test the hypotheses that most individuals with COPD in the general population are not represented in major clinical trials despite clinically significant disease with exacerbations and early death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In 105,630 adults from a Danish contemporary population-based cohort, we defined COPD as age 40 or more years, chronic respiratory symptoms, history of smoking exposure, and airflow limitation with FEV1\/FVC\u2009&amp;lt;\u20090.70. Outcomes included acute exacerbations and all-cause mortality. Symptomatic smokers without COPD were used as a reference group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Of all, 7,516 (7%) and 16,079 (15%) were symptomatic smokers with and without COPD. Only 44% of those with COPD were eligible for major clinical trials when applying FEV1\u2009&amp;lt;\u200980% predicted, smoking history of 10 or more pack-years, and no comorbid asthma as common inclusion criteria. During the median 8.9 years of follow-up, we observed 2,130 acute exacerbations and 3,973 deaths in symptomatic smokers. Compared with symptomatic smokers without COPD, multivariable-adjusted hazard ratios for exacerbations were 7.45 (95% confidence interval, 5.41\u201310.3) and 29.0 (21.1\u201339.8) in those with COPD, respectively, excluded and eligible for clinical trials. Corresponding hazard ratios for all-cause mortality were 1.21 (1.11\u20131.31) and 1.67 (1.54\u20131.81), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>More than half of individuals with COPD in the general population are excluded from major clinical trials; however, these individuals have a clinically significant disease with exacerbations and early death compared with symptomatic smokers without COPD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202110-2441oc","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T11:08:42Z","timestamp":1650366522000},"page":"271-280","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":31,"title":["Prognosis of Patients with Chronic Obstructive Pulmonary Disease Not Eligible for Major Clinical Trials"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2045-829X","authenticated-orcid":false,"given":"Yunus","family":"\u00c7olak","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine"},{"name":"The Copenhagen General Population Study, and"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1954-7220","authenticated-orcid":false,"given":"B\u00f8rge G.","family":"Nordestgaard","sequence":"additional","affiliation":[{"name":"The Copenhagen General Population Study, and"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, and"},{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital \u2013 Herlev and Gentofte, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine"},{"name":"The Copenhagen General Population Study, and"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, and"},{"name":"Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6355-6362","authenticated-orcid":false,"given":"J\u00f8rgen","family":"Vestbo","sequence":"additional","affiliation":[{"name":"Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, and Manchester University National Health Service Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-4694","authenticated-orcid":false,"given":"Shoaib","family":"Afzal","sequence":"additional","affiliation":[{"name":"The Copenhagen General Population Study, and"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, and"},{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital \u2013 Herlev and Gentofte, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"2026022021145296800_bib1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S2213-2600(17)30119-4","article-title":"Prognosis of asymptomatic and symptomatic, undiagnosed COPD in the general population in Denmark: a prospective cohort study","volume":"5","author":"\u00c7olak","year":"2017","journal-title":"Lancet Respir Med"},{"key":"2026022021145296800_bib2","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1056\/NEJMra1900475","article-title":"Update on the pathogenesis of chronic obstructive pulmonary disease","volume":"381","author":"Agust\u00ed","year":"2019","journal-title":"N Engl J Med"},{"key":"2026022021145296800_bib3","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1056\/NEJMra1900500","article-title":"Update on clinical aspects of chronic obstructive pulmonary disease","volume":"381","author":"Celli","year":"2019","journal-title":"N Engl J Med"},{"key":"2026022021145296800_bib4","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1164\/rccm.201701-0218PP","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. 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