{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:19:44Z","timestamp":1784866784231,"version":"3.55.0"},"reference-count":28,"publisher":"European Respiratory Society (ERS)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2011,4,5]]},"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:p>The oral, selective phosphodiesterase type-4 inhibitor roflumilast reduces exacerbations and improves lung function in patients with severe-to-very severe chronic obstructive pulmonary disease (COPD).<\/jats:p><jats:p>We investigated the efficacy and safety of roflumilast used concomitantly with long-acting \u03b2<jats:sub>2<\/jats:sub>-agonists (LABAs) to reduce exacerbations, and the influence of exacerbation history. Pooled data were analysed from two 12-month, placebo-controlled roflumilast (500 \u03bcg once daily) studies involving 3,091 patients with severe-to-very severe COPD.<\/jats:p><jats:p>Approximately half of patients used concomitant LABAs; 39% used concomitant short-acting muscarinic antagonists (SAMAs); 27% were frequent exacerbators (two or more exacerbations per year). Roflumilast reduced the rate of moderate or severe exacerbations, with LABA (rate ratio (RR) 0.79, 95% CI 0.69\u20130.91; p=0.001) or without LABA (RR 0.85, 95% CI 0.74\u20130.99; p=0.039) and prolonged time both to first (p=0.035 with LABA, p=0.300 without LABA) and second (p=0.018 with LABA, p=0.049 without LABA) exacerbations. Frequent exacerbators experienced a reduction in moderate or severe exacerbations (RR 0.78, 95% CI 0.66\u20130.91; p=0.002). Similarly, roflumilast remained effective with concomitant SAMA. No differences arose in adverse events between these subgroups.<\/jats:p><jats:p>Roflumilast may be used to reduce exacerbations and improve dyspnoea and lung function, without increasing adverse events in COPD patients receiving concomitant LABAs.<\/jats:p>","DOI":"10.1183\/09031936.00178710","type":"journal-article","created":{"date-parts":[[2011,7,8]],"date-time":"2011-07-08T14:48:08Z","timestamp":1310136488000},"page":"553-560","source":"Crossref","is-referenced-by-count":89,"title":["Roflumilast with long-acting \u03b2<sub>2<\/sub>-agonists for COPD: influence of exacerbation history"],"prefix":"10.1183","volume":"38","author":[{"given":"E.D.","family":"Bateman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.F.","family":"Rabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.M.A.","family":"Calverley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.M.","family":"Goehring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Brose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Bredenbr\u00f6ker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.M.","family":"Fabbri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2011,7,7]]},"reference":[{"key":"2024102020452064000_38.3.553.1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00166606"},{"key":"2024102020452064000_38.3.553.2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00109906"},{"key":"2024102020452064000_38.3.553.3","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00079409"},{"key":"2024102020452064000_38.3.553.4","unstructured":"Global Initiative for Chronic Obstructive Lung Disease. 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