{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:12:37Z","timestamp":1791022357562,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2005,10,1]],"date-time":"2005-10-01T00:00:00Z","timestamp":1128124800000},"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":[[2005,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>There is a need for new agents capable of suppressing the inflammatory response in chronic obstructive pulmonary disease. Objectives: This study evaluated the effects of roflumilast, a phosphodiesterase 4 (PDE4) inhibitor on acute lung inflammation and chronic lung changes in models of cigarette exposure in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Roflumilast was given orally either at 1 mg\/kg (R1) or at 5 mg\/kg (R5). In the acute model (five cigarettes for 20 minutes), bronchoalveolar lavage fluid (BALF) changes were investigated at 4 and 24 hours. In the chronic model (three cigarettes\/day for 7 months), morphometric and biochemical parameters were assessed at 7 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Acute exposure caused a fivefold increase in BALF neutrophils. Both doses of roflumilast partially prevented (by 30%) this increase. In addition, after smoke exposure, R1 increased BALF interleukin-10 by 79% and R5 by 129%. Chronic smoke exposure caused a 1.8-fold increase in lung macrophage density, emphysema, an increase of the mean linear intercept (+21%), a decrease of the internal surface area (\u221213%), and a drop (\u221213%) in lung desmosine content. R1 did not have any effect, whereas R5 prevented the increase in lung macrophage density by 70% and fully prevented the other changes. In addition, in the smoke-exposure group, 63% of the mice showed goblet cell metaplasia, and neither of the doses of roflumilast had any effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study shows for the first time that a PDE4 inhibitor partially ameliorates lung inflammation and fully prevents parenchymal destruction induced by cigarette smoke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200411-1549oc","type":"journal-article","created":{"date-parts":[[2005,6,16]],"date-time":"2005-06-16T20:55:30Z","timestamp":1118955330000},"page":"848-853","source":"Crossref","is-referenced-by-count":175,"title":["Roflumilast Fully Prevents Emphysema in Mice Chronically Exposed to Cigarette Smoke"],"prefix":"10.1093","volume":"172","author":[{"given":"Piero A.","family":"Martorana","sequence":"first","affiliation":[{"name":"Department of Physiopathology and Experimental Medicine, University of Siena, Siena, Italy; and ALTANA Pharma, Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Beume","sequence":"additional","affiliation":[{"name":"Department of Physiopathology and Experimental Medicine, University of Siena, Siena, Italy; and ALTANA Pharma, Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Lucattelli","sequence":"additional","affiliation":[{"name":"Department of Physiopathology and Experimental Medicine, University of Siena, Siena, Italy; and ALTANA Pharma, Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Wollin","sequence":"additional","affiliation":[{"name":"Department of Physiopathology and Experimental Medicine, University of Siena, Siena, Italy; and ALTANA Pharma, Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lungarella","sequence":"additional","affiliation":[{"name":"Department of Physiopathology and Experimental Medicine, University of Siena, Siena, Italy; and ALTANA Pharma, Konstanz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,10,1]]},"reference":[{"key":"2026032606061152100_BIB1","first-page":"1498","volume-title":"Lancet","year":"1997"},{"key":"2026032606061152100_BIB2","first-page":"105","volume-title":"J COPD","year":"2004"},{"key":"2026032606061152100_BIB3"},{"key":"2026032606061152100_BIB4","first-page":"861","volume-title":"Am J Respir Crit Care Med","year":"1996"},{"key":"2026032606061152100_BIB5"},{"key":"2026032606061152100_BIB6","first-page":"1635","volume-title":"Am J Respir Crit Care Med","year":"1999"},{"key":"2026032606061152100_BIB7","first-page":"115","volume-title":"Respir 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