{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:33:49Z","timestamp":1790094829761,"version":"4.0.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Predefined, pooled analyses of REACT (Roflumilast in the Prevention of COPD Exacerbations While Taking Appropriate Combination Treatment; NCT01329029) and RE2SPOND (Roflumilast Effect on Exacerbations in Patients on Dual [LABA\/ICS] Therapy; NCT01443845) multicenter, randomized, double-blind, placebo-controlled studies. The primary endpoint was rate of moderate or severe exacerbations per patient per year.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In the overall intention-to-treat population (n\u2009=\u20094,287), roflumilast reduced moderate or severe exacerbations by 12.3% (rate ratio, 0.88, 95% confidence interval, 0.80\u20130.97; P\u2009=\u20090.0086) and severe exacerbations by 16.1% (0.84; 0.71\u20130.99; P\u2009=\u20090.0409) versus placebo. The reduction in moderate or severe exacerbations with roflumilast was most pronounced in patients who had been hospitalized for an exacerbation in the prior year (0.74; 0.63\u20130.88; P\u2009=\u20090.0005); had more than two exacerbations in the prior year (0.79; 0.65\u20130.96; P\u2009=\u20090.0160); or had baseline eosinophils \u2265150 cells\/\u03bcl (0.81; 0.71\u20130.93; P\u2009=\u20090.0020), \u2265150 to &amp;lt;300 cells\/\u03bcl (0.84; 0.71\u20130.98; P\u2009=\u20090.0282), or \u2265300 cells\/\u03bcl (0.77; 0.61\u20130.97; P\u2009=\u20090.0264). Similar subgroup results were noted for severe exacerbations. In patients with prior hospitalization and higher baseline blood eosinophil concentrations, roflumilast reduced moderate or severe exacerbations by 34.5% at \u2265150 cells\/\u03bcl (0.65; 0.52\u20130.82; P\u2009=\u20090.0003) and 42.7% at \u2265300 cells\/\u03bcl (0.57; 0.37\u20130.88; P\u2009=\u20090.0111) versus placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This prespecified, pooled analysis confirms the benefit of roflumilast in decreasing exacerbations in patients with prior hospitalization for exacerbation, greater exacerbation frequency, and higher (\u2265150 cells\/\u03bcl, \u2265150 to &amp;lt;300 cells\/\u03bcl, or \u2265300 cells\/\u03bcl) baseline blood eosinophil count.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201712-2493oc","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T17:53:23Z","timestamp":1526406803000},"page":"1268-1278","source":"Crossref","is-referenced-by-count":59,"title":["Determinants of Response to Roflumilast in Severe Chronic Obstructive Pulmonary Disease: Pooled Analysis of Two Randomized Trials"],"prefix":"10.1093","volume":"198","author":[{"given":"Fernando J.","family":"Martinez","sequence":"first","affiliation":[{"name":"Weill Cornell Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus F.","family":"Rabe","sequence":"additional","affiliation":[{"name":"LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M. 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