Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD
Background:Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for t...
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| Veröffentlicht in: | Thorax 2007-12, Vol.62 (12), p.1081-1087 |
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| creator | Grootendorst, Diana C Gauw, Stefanie A Verhoosel, Renate M Sterk, Peter J Hospers, Jeannette J Bredenbröker, Dirk Bethke, Thomas D Hiemstra, Pieter S Rabe, Klaus F |
| description | Background:Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD.Methods:In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV1) 61.0 (12.6)% predicted) received 500 μg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly.Results:Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and α2-macroglobulin in sputum and the release of tumour necrosis factor α from blood cells were significantly reduced by roflumilast compared with placebo treatment (p |
| doi_str_mv | 10.1136/thx.2006.075937 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2094292</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20491193</sourcerecordid><originalsourceid>FETCH-LOGICAL-b553t-ade6ade44c0d0e6f999c34648ff6cd3647c6dd3ba241a056c0c1d0e051f9ab333</originalsourceid><addsrcrecordid>eNqFkc-L1DAcxYso7rh69iYB0YPQ2aRJk-YiyOy6CsPuKOo1pGlqM7ZJTVLd_e9N6bA_vOwhhPD9fB_v5WXZSwTXCGF6ErurdQEhXUNWcsweZStEaJXjgtPH2QpCAnOKGT3KnoWwhxBWCLGn2RFiJcOE0FU2fNXNpKJxFhgLwjjFaQBWT9G7sTM9kLYB2gVjl6edhlr7AOprEDsNdqdnJO11pjbReeBd20-D6WWIs9ooo9E2BvDXxA5sLnenz7MnreyDfnG4j7PvH8--bT7l28vzz5sP27wuSxxz2WiaDiEKNlDTlnOuMKGkaluqGkwJU7RpcC0LgiQsqYIKJRCWqOWyxhgfZ-8X3XGqB92o5MLLXozeDNJfCyeNuD-xphM_3R9RQE4KXiSBtwcB735POkQxmKB030ur3RQErUrMSvowWEDCEeKzpdf_gXs3eZt-QSBWIUYZpTRRJwulvAvB6_bGM4JiblykxsXcuFgaTxuv7ka95Q8VJ-DNAZBByb710ioTbjleVAUmc5J84UyI-upmLv0vQVkKKy5-bARB1e7iy_lWkMS_W_h62D_o8h_kj9I-</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1781767666</pqid></control><display><type>article</type><title>Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD</title><source>BMJ Journals Online Archive</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Grootendorst, Diana C ; Gauw, Stefanie A ; Verhoosel, Renate M ; Sterk, Peter J ; Hospers, Jeannette J ; Bredenbröker, Dirk ; Bethke, Thomas D ; Hiemstra, Pieter S ; Rabe, Klaus F</creator><creatorcontrib>Grootendorst, Diana C ; Gauw, Stefanie A ; Verhoosel, Renate M ; Sterk, Peter J ; Hospers, Jeannette J ; Bredenbröker, Dirk ; Bethke, Thomas D ; Hiemstra, Pieter S ; Rabe, Klaus F</creatorcontrib><description>Background:Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD.Methods:In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV1) 61.0 (12.6)% predicted) received 500 μg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly.Results:Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and α2-macroglobulin in sputum and the release of tumour necrosis factor α from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV1 improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018).Conclusion:PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV1.</description><identifier>ISSN: 0040-6376</identifier><identifier>EISSN: 1468-3296</identifier><identifier>DOI: 10.1136/thx.2006.075937</identifier><identifier>PMID: 17573446</identifier><identifier>CODEN: THORA7</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Thoracic Society</publisher><subject>Aged ; Aminopyridines - therapeutic use ; Benzamides - therapeutic use ; Biological and medical sciences ; Biomarkers - blood ; Cell Count ; Chronic Obstructive Pulmonary Disease ; Chronic obstructive pulmonary disease, asthma ; Cross-Over Studies ; Cyclopropanes - therapeutic use ; Double-Blind Method ; Enzymes ; Eosinophils ; Female ; Forced Expiratory Volume - physiology ; Humans ; Inflammation ; Laboratories ; Male ; Medical sciences ; Microcirculation ; Middle Aged ; Mortality ; Neutrophils ; Phosphodiesterase 4 Inhibitors ; Pneumology ; Pulmonary Disease, Chronic Obstructive - drug therapy ; Pulmonary Disease, Chronic Obstructive - pathology ; Smooth muscle ; Sputum - cytology ; Studies ; Tumor necrosis factor-TNF</subject><ispartof>Thorax, 2007-12, Vol.62 (12), p.1081-1087</ispartof><rights>2007 BMJ Publishing Group Ltd and British Thoracic Society</rights><rights>2007 INIST-CNRS</rights><rights>Copyright: 2007 2007 BMJ Publishing Group Ltd and British Thoracic Society</rights><rights>Copyright © 2007 BMJ Publishing Group Ltd and British Thoracic Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b553t-ade6ade44c0d0e6f999c34648ff6cd3647c6dd3ba241a056c0c1d0e051f9ab333</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://thorax.bmj.com/content/62/12/1081.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttps://thorax.bmj.com/content/62/12/1081.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,230,314,723,776,780,881,3183,23552,27903,27904,53769,53771,77346,77377</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19282342$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17573446$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Grootendorst, Diana C</creatorcontrib><creatorcontrib>Gauw, Stefanie A</creatorcontrib><creatorcontrib>Verhoosel, Renate M</creatorcontrib><creatorcontrib>Sterk, Peter J</creatorcontrib><creatorcontrib>Hospers, Jeannette J</creatorcontrib><creatorcontrib>Bredenbröker, Dirk</creatorcontrib><creatorcontrib>Bethke, Thomas D</creatorcontrib><creatorcontrib>Hiemstra, Pieter S</creatorcontrib><creatorcontrib>Rabe, Klaus F</creatorcontrib><title>Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD</title><title>Thorax</title><addtitle>Thorax</addtitle><description>Background:Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD.Methods:In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV1) 61.0 (12.6)% predicted) received 500 μg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly.Results:Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and α2-macroglobulin in sputum and the release of tumour necrosis factor α from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV1 improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018).Conclusion:PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV1.</description><subject>Aged</subject><subject>Aminopyridines - therapeutic use</subject><subject>Benzamides - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Cell Count</subject><subject>Chronic Obstructive Pulmonary Disease</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>Cross-Over Studies</subject><subject>Cyclopropanes - therapeutic use</subject><subject>Double-Blind Method</subject><subject>Enzymes</subject><subject>Eosinophils</subject><subject>Female</subject><subject>Forced Expiratory Volume - physiology</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Laboratories</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microcirculation</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Neutrophils</subject><subject>Phosphodiesterase 4 Inhibitors</subject><subject>Pneumology</subject><subject>Pulmonary Disease, Chronic Obstructive - drug therapy</subject><subject>Pulmonary Disease, Chronic Obstructive - pathology</subject><subject>Smooth muscle</subject><subject>Sputum - cytology</subject><subject>Studies</subject><subject>Tumor necrosis factor-TNF</subject><issn>0040-6376</issn><issn>1468-3296</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc-L1DAcxYso7rh69iYB0YPQ2aRJk-YiyOy6CsPuKOo1pGlqM7ZJTVLd_e9N6bA_vOwhhPD9fB_v5WXZSwTXCGF6ErurdQEhXUNWcsweZStEaJXjgtPH2QpCAnOKGT3KnoWwhxBWCLGn2RFiJcOE0FU2fNXNpKJxFhgLwjjFaQBWT9G7sTM9kLYB2gVjl6edhlr7AOprEDsNdqdnJO11pjbReeBd20-D6WWIs9ooo9E2BvDXxA5sLnenz7MnreyDfnG4j7PvH8--bT7l28vzz5sP27wuSxxz2WiaDiEKNlDTlnOuMKGkaluqGkwJU7RpcC0LgiQsqYIKJRCWqOWyxhgfZ-8X3XGqB92o5MLLXozeDNJfCyeNuD-xphM_3R9RQE4KXiSBtwcB735POkQxmKB030ur3RQErUrMSvowWEDCEeKzpdf_gXs3eZt-QSBWIUYZpTRRJwulvAvB6_bGM4JiblykxsXcuFgaTxuv7ka95Q8VJ-DNAZBByb710ioTbjleVAUmc5J84UyI-upmLv0vQVkKKy5-bARB1e7iy_lWkMS_W_h62D_o8h_kj9I-</recordid><startdate>20071201</startdate><enddate>20071201</enddate><creator>Grootendorst, Diana C</creator><creator>Gauw, Stefanie A</creator><creator>Verhoosel, Renate M</creator><creator>Sterk, Peter J</creator><creator>Hospers, Jeannette J</creator><creator>Bredenbröker, Dirk</creator><creator>Bethke, Thomas D</creator><creator>Hiemstra, Pieter S</creator><creator>Rabe, Klaus F</creator><general>BMJ Publishing Group Ltd and British Thoracic Society</general><general>BMJ</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20071201</creationdate><title>Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD</title><author>Grootendorst, Diana C ; Gauw, Stefanie A ; Verhoosel, Renate M ; Sterk, Peter J ; Hospers, Jeannette J ; Bredenbröker, Dirk ; Bethke, Thomas D ; Hiemstra, Pieter S ; Rabe, Klaus F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b553t-ade6ade44c0d0e6f999c34648ff6cd3647c6dd3ba241a056c0c1d0e051f9ab333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Aged</topic><topic>Aminopyridines - therapeutic use</topic><topic>Benzamides - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Cell Count</topic><topic>Chronic Obstructive Pulmonary Disease</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>Cross-Over Studies</topic><topic>Cyclopropanes - therapeutic use</topic><topic>Double-Blind Method</topic><topic>Enzymes</topic><topic>Eosinophils</topic><topic>Female</topic><topic>Forced Expiratory Volume - physiology</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Laboratories</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microcirculation</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Neutrophils</topic><topic>Phosphodiesterase 4 Inhibitors</topic><topic>Pneumology</topic><topic>Pulmonary Disease, Chronic Obstructive - drug therapy</topic><topic>Pulmonary Disease, Chronic Obstructive - pathology</topic><topic>Smooth muscle</topic><topic>Sputum - cytology</topic><topic>Studies</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grootendorst, Diana C</creatorcontrib><creatorcontrib>Gauw, Stefanie A</creatorcontrib><creatorcontrib>Verhoosel, Renate M</creatorcontrib><creatorcontrib>Sterk, Peter J</creatorcontrib><creatorcontrib>Hospers, Jeannette J</creatorcontrib><creatorcontrib>Bredenbröker, Dirk</creatorcontrib><creatorcontrib>Bethke, Thomas D</creatorcontrib><creatorcontrib>Hiemstra, Pieter S</creatorcontrib><creatorcontrib>Rabe, Klaus F</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Thorax</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grootendorst, Diana C</au><au>Gauw, Stefanie A</au><au>Verhoosel, Renate M</au><au>Sterk, Peter J</au><au>Hospers, Jeannette J</au><au>Bredenbröker, Dirk</au><au>Bethke, Thomas D</au><au>Hiemstra, Pieter S</au><au>Rabe, Klaus F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD</atitle><jtitle>Thorax</jtitle><addtitle>Thorax</addtitle><date>2007-12-01</date><risdate>2007</risdate><volume>62</volume><issue>12</issue><spage>1081</spage><epage>1087</epage><pages>1081-1087</pages><issn>0040-6376</issn><eissn>1468-3296</eissn><coden>THORA7</coden><abstract>Background:Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD.Methods:In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV1) 61.0 (12.6)% predicted) received 500 μg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly.Results:Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and α2-macroglobulin in sputum and the release of tumour necrosis factor α from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV1 improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018).Conclusion:PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV1.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Thoracic Society</pub><pmid>17573446</pmid><doi>10.1136/thx.2006.075937</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | BMJ Journals Online Archive; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Aged Aminopyridines - therapeutic use Benzamides - therapeutic use Biological and medical sciences Biomarkers - blood Cell Count Chronic Obstructive Pulmonary Disease Chronic obstructive pulmonary disease, asthma Cross-Over Studies Cyclopropanes - therapeutic use Double-Blind Method Enzymes Eosinophils Female Forced Expiratory Volume - physiology Humans Inflammation Laboratories Male Medical sciences Microcirculation Middle Aged Mortality Neutrophils Phosphodiesterase 4 Inhibitors Pneumology Pulmonary Disease, Chronic Obstructive - drug therapy Pulmonary Disease, Chronic Obstructive - pathology Smooth muscle Sputum - cytology Studies Tumor necrosis factor-TNF |
| title | Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD |
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