{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:12:46Z","timestamp":1789762366876,"version":"4.0.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":874,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute of Health Research","doi-asserted-by":"crossref","award":["RP-PG-0109-10056"],"award-info":[{"award-number":["RP-PG-0109-10056"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute of Health Research","doi-asserted-by":"crossref","award":["RP-PG-0109-10056"],"award-info":[{"award-number":["RP-PG-0109-10056"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations, but there is a paucity of evidence for other antibiotic classes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess whether 12-month use of doxycycline reduces the exacerbation rate in people with COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>People with moderate to very severe COPD and an exacerbation history were recruited from three UK centers and randomized to 12\u2009months of doxycycline 100\u2009mg once daily or placebo. The primary study outcome was the exacerbation rate per person-year.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 222 people were randomized. Baseline mean FEV1 was 1.35\u2009L (SD, 0.35\u2009L), 52.5% predicted (SD, 15.9% predicted). The median number of treated exacerbations in the year before the study was 2 (SD, 1\u20134). A total of 71% of patients reported two or more exacerbations, and 81% were already prescribed inhaled corticosteroids at baseline. The COPD exacerbation rate did not differ between the groups (doxycycline\/placebo rate ratio [RR], 0.86; 95% confidence interval [CI], 0.67\u20131.10; P\u2009=\u20090.23). No difference was seen if only treated exacerbations or hospitalizations were considered. In preplanned subgroup analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR, 0.36; 95% CI, 0.15\u20130.85; P\u2009=\u20090.019) and in those with an eosinophil count &amp;lt;300\u2009cells\/\u03bcl (RR, 0.50; 95% CI, 0.29\u20130.84; P\u2009=\u20090.01). Health status measured by St. George\u2019s Respiratory Questionnaire was 5.2 points worse in the doxycycline group at 12\u2009months (P\u2009&amp;lt;\u20090.007).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Doxycycline did not significantly reduce the exacerbation rate, over 12\u2009months, in participants with COPD who exacerbated regularly, but it may have benefitted those with more severe COPD or blood eosinophil counts &amp;lt;300\u2009cells\/\u03bcl.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT02305940).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202212-2287oc","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T17:29:58Z","timestamp":1689355798000},"page":"549-558","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":14,"title":["A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-7533","authenticated-orcid":false,"given":"James P.","family":"Allinson","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"},{"name":"Department of Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben H.","family":"Vlies","sequence":"additional","affiliation":[{"name":"School of Aging and Chronic Disease and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6297-0665","authenticated-orcid":false,"given":"Simon E.","family":"Brill","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Law","sequence":"additional","affiliation":[{"name":"Hub for Trials Methodology Research, Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girvan","family":"Burnside","sequence":"additional","affiliation":[{"name":"Department of Health Data Science, University of Liverpool, Liverpool, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-9513","authenticated-orcid":false,"given":"Lydia J.","family":"Finney","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Alves-Moreira","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5538-4190","authenticated-orcid":false,"given":"Gavin C.","family":"Donaldson","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-9993","authenticated-orcid":false,"given":"Peter M. 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