Antiinflammatory Effects of the Phosphodiesterase-4 Inhibitor Cilomilast (Ariflo) in Chronic Obstructive Pulmonary Disease
Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function in chronic obstructive pulmonary disease (COPD). We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast, 15 mg two times a day, or placebo for 12 weeks. I...
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| Veröffentlicht in: | American journal of respiratory and critical care medicine 2003-10, Vol.168 (8), p.976-982 |
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| creator | Gamble, Elizabeth Grootendorst, Diana C Brightling, Christopher E Troy, Susannah Qiu, Yusheng Zhu, Jie Parker, Debbie Matin, Dean Majumdar, Swati Vignola, Antonio M Kroegel, Claus Morell, Ferran Hansel, Trevor T Rennard, Stephen I Compton, Christopher Amit, Ohad Tat, Tri Edelson, Jeffrey Pavord, Ian D Rabe, Klaus F Barnes, Neil C Jeffery, Peter K |
| description | Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function in chronic obstructive pulmonary disease (COPD). We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast, 15 mg two times a day, or placebo for 12 weeks. Induced sputum differential cell counts were obtained at baseline and at five further visits. Interleukin-8 and neutrophil elastase were measured in sputum supernatant. Bronchial biopsies obtained at baseline and at Week 10 were immunostained and counted for neutrophils, CD8+ and CD4+ T-lymphocyte subsets, and CD68+ macrophages. Cells expressing the genes for interleukin-8 and tumor necrosis factor-alpha were identified by in situ hybridization and quantified. Compared with placebo, analysis of variance (ANOVA) of the change from baseline showed that cilomilast did not alter any sputum endpoint or FEV1. However, bronchial biopsies demonstrated that cilomilast treatment was associated with reductions in CD8+ (p = 0.001; ANOVA) and CD68+ cells (p < 0.05; ANOVA). In addition, by Poisson analysis, comparison of cell counts analyzed as a ratio of active to placebo demonstrated reductions of CD8+ (48% p < 0.01) and CD68+ (47% p = 0.001) cells. This is the first demonstration of reduction by any agent of airway tissue inflammatory cells characteristic of COPD. Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease. |
| doi_str_mv | 10.1164/rccm.200212-1490OC |
| format | Article |
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We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast, 15 mg two times a day, or placebo for 12 weeks. Induced sputum differential cell counts were obtained at baseline and at five further visits. Interleukin-8 and neutrophil elastase were measured in sputum supernatant. Bronchial biopsies obtained at baseline and at Week 10 were immunostained and counted for neutrophils, CD8+ and CD4+ T-lymphocyte subsets, and CD68+ macrophages. Cells expressing the genes for interleukin-8 and tumor necrosis factor-alpha were identified by in situ hybridization and quantified. Compared with placebo, analysis of variance (ANOVA) of the change from baseline showed that cilomilast did not alter any sputum endpoint or FEV1. However, bronchial biopsies demonstrated that cilomilast treatment was associated with reductions in CD8+ (p = 0.001; ANOVA) and CD68+ cells (p < 0.05; ANOVA). In addition, by Poisson analysis, comparison of cell counts analyzed as a ratio of active to placebo demonstrated reductions of CD8+ (48% p < 0.01) and CD68+ (47% p = 0.001) cells. This is the first demonstration of reduction by any agent of airway tissue inflammatory cells characteristic of COPD. Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease.</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.200212-1490OC</identifier><identifier>PMID: 12816740</identifier><language>eng</language><publisher>New York, NY: Am Thoracic Soc</publisher><subject>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors ; Adult ; Aged ; Aged, 80 and over ; Anti-Inflammatory Agents - immunology ; Anti-Inflammatory Agents - therapeutic use ; Antigens, CD - analysis ; Antigens, CD - drug effects ; Antigens, Differentiation, Myelomonocytic - analysis ; Antigens, Differentiation, Myelomonocytic - drug effects ; Biological and medical sciences ; Biopsy ; Bronchodilator Agents - immunology ; Bronchodilator Agents - therapeutic use ; Carboxylic Acids ; CD4-Positive T-Lymphocytes - drug effects ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; Cyclic Nucleotide Phosphodiesterases, Type 4 ; Cyclohexanecarboxylic Acids ; Double-Blind Method ; Female ; Forced Expiratory Volume - drug effects ; Humans ; Interleukin-8 - analysis ; Interleukin-8 - immunology ; Leukocyte Count ; Leukocyte Elastase - analysis ; Leukocyte Elastase - drug effects ; Male ; Medical sciences ; Middle Aged ; Nitriles ; Pharmacology. Drug treatments ; Phosphodiesterase Inhibitors - immunology ; Phosphodiesterase Inhibitors - therapeutic use ; Pulmonary Disease, Chronic Obstructive - drug therapy ; Pulmonary Disease, Chronic Obstructive - immunology ; Pulmonary Disease, Chronic Obstructive - physiopathology ; Respiratory system ; Sputum - chemistry ; Sputum - cytology ; Treatment Outcome</subject><ispartof>American journal of respiratory and critical care medicine, 2003-10, Vol.168 (8), p.976-982</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright American Thoracic Society Oct 15, 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-a98497408efd24bdffab2f12159d4953afe0e53d18a3cec5f0d6a9e683e3d9c33</citedby><cites>FETCH-LOGICAL-c390t-a98497408efd24bdffab2f12159d4953afe0e53d18a3cec5f0d6a9e683e3d9c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,4025,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15205895$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12816740$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gamble, Elizabeth</creatorcontrib><creatorcontrib>Grootendorst, Diana C</creatorcontrib><creatorcontrib>Brightling, Christopher E</creatorcontrib><creatorcontrib>Troy, Susannah</creatorcontrib><creatorcontrib>Qiu, Yusheng</creatorcontrib><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Parker, Debbie</creatorcontrib><creatorcontrib>Matin, Dean</creatorcontrib><creatorcontrib>Majumdar, Swati</creatorcontrib><creatorcontrib>Vignola, Antonio M</creatorcontrib><creatorcontrib>Kroegel, Claus</creatorcontrib><creatorcontrib>Morell, Ferran</creatorcontrib><creatorcontrib>Hansel, Trevor T</creatorcontrib><creatorcontrib>Rennard, Stephen I</creatorcontrib><creatorcontrib>Compton, Christopher</creatorcontrib><creatorcontrib>Amit, Ohad</creatorcontrib><creatorcontrib>Tat, Tri</creatorcontrib><creatorcontrib>Edelson, Jeffrey</creatorcontrib><creatorcontrib>Pavord, Ian D</creatorcontrib><creatorcontrib>Rabe, Klaus F</creatorcontrib><creatorcontrib>Barnes, Neil C</creatorcontrib><creatorcontrib>Jeffery, Peter K</creatorcontrib><title>Antiinflammatory Effects of the Phosphodiesterase-4 Inhibitor Cilomilast (Ariflo) in Chronic Obstructive Pulmonary Disease</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function in chronic obstructive pulmonary disease (COPD). We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast, 15 mg two times a day, or placebo for 12 weeks. Induced sputum differential cell counts were obtained at baseline and at five further visits. Interleukin-8 and neutrophil elastase were measured in sputum supernatant. Bronchial biopsies obtained at baseline and at Week 10 were immunostained and counted for neutrophils, CD8+ and CD4+ T-lymphocyte subsets, and CD68+ macrophages. Cells expressing the genes for interleukin-8 and tumor necrosis factor-alpha were identified by in situ hybridization and quantified. Compared with placebo, analysis of variance (ANOVA) of the change from baseline showed that cilomilast did not alter any sputum endpoint or FEV1. However, bronchial biopsies demonstrated that cilomilast treatment was associated with reductions in CD8+ (p = 0.001; ANOVA) and CD68+ cells (p < 0.05; ANOVA). In addition, by Poisson analysis, comparison of cell counts analyzed as a ratio of active to placebo demonstrated reductions of CD8+ (48% p < 0.01) and CD68+ (47% p = 0.001) cells. This is the first demonstration of reduction by any agent of airway tissue inflammatory cells characteristic of COPD. Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease.</description><subject>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anti-Inflammatory Agents - immunology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Antigens, CD - analysis</subject><subject>Antigens, CD - drug effects</subject><subject>Antigens, Differentiation, Myelomonocytic - analysis</subject><subject>Antigens, Differentiation, Myelomonocytic - drug effects</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Bronchodilator Agents - immunology</subject><subject>Bronchodilator Agents - therapeutic use</subject><subject>Carboxylic Acids</subject><subject>CD4-Positive T-Lymphocytes - drug effects</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 4</subject><subject>Cyclohexanecarboxylic Acids</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Forced Expiratory Volume - drug effects</subject><subject>Humans</subject><subject>Interleukin-8 - analysis</subject><subject>Interleukin-8 - immunology</subject><subject>Leukocyte Count</subject><subject>Leukocyte Elastase - analysis</subject><subject>Leukocyte Elastase - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nitriles</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphodiesterase Inhibitors - immunology</subject><subject>Phosphodiesterase Inhibitors - therapeutic use</subject><subject>Pulmonary Disease, Chronic Obstructive - drug therapy</subject><subject>Pulmonary Disease, Chronic Obstructive - immunology</subject><subject>Pulmonary Disease, Chronic Obstructive - physiopathology</subject><subject>Respiratory system</subject><subject>Sputum - chemistry</subject><subject>Sputum - cytology</subject><subject>Treatment Outcome</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpdkU9rFTEUxYMotn31C7iQICh2MTV_Z5LlY6y2UHguKrgLmUzi5JGZPJMZRT9985gHha7uXfzOufdwAHiL0TXGNfucjBmvCUIEkwoziXbtC3COOeUVkw16WXbU0Iox-fMMXOS8RwgTgdFrcHacdcPQOfi_nWbvJxf0OOo5pn_wxjlr5gyjg_Ng4fch5sMQe2_zbJPOtmLwbhp85wsNWx_i6IPOM_y0Td6FeAX9BNshxckbuOvynBYz-z_FaAljnHS58MVnW4wuwSunQ7ZvTnMDfny9eWhvq_vdt7t2e18ZKtFcaSlKHIaEdT1hXe-c7ojDBHPZM8mpdhZZTnssNDXWcIf6WktbC2ppLw2lG_Bx9T2k-HspMdTos7Eh6MnGJauGNzXiQhTw_TNwH5c0ld8UlpJzwRgpEFkhk2LOyTp1SH4ssRRG6liLOtai1lrUWksRvTs5L91o-yfJqYcCfDgBOhsdXNKT8fmJ46R8WMJuwNXKDf7X8Ncnq_KoQyi2WOn98TKuhRJKNjV9BK9gprI</recordid><startdate>20031015</startdate><enddate>20031015</enddate><creator>Gamble, Elizabeth</creator><creator>Grootendorst, Diana C</creator><creator>Brightling, Christopher E</creator><creator>Troy, Susannah</creator><creator>Qiu, Yusheng</creator><creator>Zhu, Jie</creator><creator>Parker, Debbie</creator><creator>Matin, Dean</creator><creator>Majumdar, Swati</creator><creator>Vignola, Antonio M</creator><creator>Kroegel, Claus</creator><creator>Morell, Ferran</creator><creator>Hansel, Trevor T</creator><creator>Rennard, Stephen I</creator><creator>Compton, Christopher</creator><creator>Amit, Ohad</creator><creator>Tat, Tri</creator><creator>Edelson, Jeffrey</creator><creator>Pavord, Ian D</creator><creator>Rabe, Klaus F</creator><creator>Barnes, Neil C</creator><creator>Jeffery, Peter K</creator><general>Am Thoracic Soc</general><general>American Lung Association</general><general>American Thoracic Society</general><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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20031015</creationdate><title>Antiinflammatory Effects of the Phosphodiesterase-4 Inhibitor Cilomilast (Ariflo) in Chronic Obstructive Pulmonary Disease</title><author>Gamble, Elizabeth ; Grootendorst, Diana C ; Brightling, Christopher E ; Troy, Susannah ; Qiu, Yusheng ; Zhu, Jie ; Parker, Debbie ; Matin, Dean ; Majumdar, Swati ; Vignola, Antonio M ; Kroegel, Claus ; Morell, Ferran ; Hansel, Trevor T ; Rennard, Stephen I ; Compton, Christopher ; Amit, Ohad ; Tat, Tri ; Edelson, Jeffrey ; Pavord, Ian D ; Rabe, Klaus F ; Barnes, Neil C ; Jeffery, Peter K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-a98497408efd24bdffab2f12159d4953afe0e53d18a3cec5f0d6a9e683e3d9c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anti-Inflammatory Agents - immunology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Antigens, CD - analysis</topic><topic>Antigens, CD - drug effects</topic><topic>Antigens, Differentiation, Myelomonocytic - analysis</topic><topic>Antigens, Differentiation, Myelomonocytic - drug effects</topic><topic>Biological and medical sciences</topic><topic>Biopsy</topic><topic>Bronchodilator Agents - immunology</topic><topic>Bronchodilator Agents - therapeutic use</topic><topic>Carboxylic Acids</topic><topic>CD4-Positive T-Lymphocytes - drug effects</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cyclic Nucleotide Phosphodiesterases, Type 4</topic><topic>Cyclohexanecarboxylic Acids</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Forced Expiratory Volume - drug effects</topic><topic>Humans</topic><topic>Interleukin-8 - analysis</topic><topic>Interleukin-8 - immunology</topic><topic>Leukocyte Count</topic><topic>Leukocyte Elastase - analysis</topic><topic>Leukocyte Elastase - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nitriles</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphodiesterase Inhibitors - immunology</topic><topic>Phosphodiesterase Inhibitors - therapeutic use</topic><topic>Pulmonary Disease, Chronic Obstructive - drug therapy</topic><topic>Pulmonary Disease, Chronic Obstructive - immunology</topic><topic>Pulmonary Disease, Chronic Obstructive - physiopathology</topic><topic>Respiratory system</topic><topic>Sputum - chemistry</topic><topic>Sputum - cytology</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gamble, Elizabeth</creatorcontrib><creatorcontrib>Grootendorst, Diana C</creatorcontrib><creatorcontrib>Brightling, Christopher E</creatorcontrib><creatorcontrib>Troy, Susannah</creatorcontrib><creatorcontrib>Qiu, Yusheng</creatorcontrib><creatorcontrib>Zhu, Jie</creatorcontrib><creatorcontrib>Parker, Debbie</creatorcontrib><creatorcontrib>Matin, Dean</creatorcontrib><creatorcontrib>Majumdar, Swati</creatorcontrib><creatorcontrib>Vignola, Antonio M</creatorcontrib><creatorcontrib>Kroegel, Claus</creatorcontrib><creatorcontrib>Morell, Ferran</creatorcontrib><creatorcontrib>Hansel, Trevor T</creatorcontrib><creatorcontrib>Rennard, Stephen I</creatorcontrib><creatorcontrib>Compton, Christopher</creatorcontrib><creatorcontrib>Amit, Ohad</creatorcontrib><creatorcontrib>Tat, Tri</creatorcontrib><creatorcontrib>Edelson, Jeffrey</creatorcontrib><creatorcontrib>Pavord, Ian D</creatorcontrib><creatorcontrib>Rabe, Klaus F</creatorcontrib><creatorcontrib>Barnes, Neil C</creatorcontrib><creatorcontrib>Jeffery, Peter K</creatorcontrib><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>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gamble, Elizabeth</au><au>Grootendorst, Diana C</au><au>Brightling, Christopher E</au><au>Troy, Susannah</au><au>Qiu, Yusheng</au><au>Zhu, Jie</au><au>Parker, Debbie</au><au>Matin, Dean</au><au>Majumdar, Swati</au><au>Vignola, Antonio M</au><au>Kroegel, Claus</au><au>Morell, Ferran</au><au>Hansel, Trevor T</au><au>Rennard, Stephen I</au><au>Compton, Christopher</au><au>Amit, Ohad</au><au>Tat, Tri</au><au>Edelson, Jeffrey</au><au>Pavord, Ian D</au><au>Rabe, Klaus F</au><au>Barnes, Neil C</au><au>Jeffery, Peter K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiinflammatory Effects of the Phosphodiesterase-4 Inhibitor Cilomilast (Ariflo) in Chronic Obstructive Pulmonary Disease</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2003-10-15</date><risdate>2003</risdate><volume>168</volume><issue>8</issue><spage>976</spage><epage>982</epage><pages>976-982</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>Cilomilast (Ariflo), a new oral phosphodiesterase-4 selective inhibitor, improves lung function in chronic obstructive pulmonary disease (COPD). We have evaluated its antiinflammatory effects in 59 patients with COPD randomized to receive cilomilast, 15 mg two times a day, or placebo for 12 weeks. Induced sputum differential cell counts were obtained at baseline and at five further visits. Interleukin-8 and neutrophil elastase were measured in sputum supernatant. Bronchial biopsies obtained at baseline and at Week 10 were immunostained and counted for neutrophils, CD8+ and CD4+ T-lymphocyte subsets, and CD68+ macrophages. Cells expressing the genes for interleukin-8 and tumor necrosis factor-alpha were identified by in situ hybridization and quantified. Compared with placebo, analysis of variance (ANOVA) of the change from baseline showed that cilomilast did not alter any sputum endpoint or FEV1. However, bronchial biopsies demonstrated that cilomilast treatment was associated with reductions in CD8+ (p = 0.001; ANOVA) and CD68+ cells (p < 0.05; ANOVA). In addition, by Poisson analysis, comparison of cell counts analyzed as a ratio of active to placebo demonstrated reductions of CD8+ (48% p < 0.01) and CD68+ (47% p = 0.001) cells. This is the first demonstration of reduction by any agent of airway tissue inflammatory cells characteristic of COPD. Phosphodiesterase-4 inhibitors represent a promising new class of substances for use in antiinflammatory treatment of this disease.</abstract><cop>New York, NY</cop><pub>Am Thoracic Soc</pub><pmid>12816740</pmid><doi>10.1164/rccm.200212-1490OC</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1073-449X |
| ispartof | American journal of respiratory and critical care medicine, 2003-10, Vol.168 (8), p.976-982 |
| issn | 1073-449X 1535-4970 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_75760588 |
| source | MEDLINE; Journals@Ovid Complete; American Thoracic Society (ATS) Journals Online; EZB-FREE-00999 freely available EZB journals |
| subjects | 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors Adult Aged Aged, 80 and over Anti-Inflammatory Agents - immunology Anti-Inflammatory Agents - therapeutic use Antigens, CD - analysis Antigens, CD - drug effects Antigens, Differentiation, Myelomonocytic - analysis Antigens, Differentiation, Myelomonocytic - drug effects Biological and medical sciences Biopsy Bronchodilator Agents - immunology Bronchodilator Agents - therapeutic use Carboxylic Acids CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology Cyclic Nucleotide Phosphodiesterases, Type 4 Cyclohexanecarboxylic Acids Double-Blind Method Female Forced Expiratory Volume - drug effects Humans Interleukin-8 - analysis Interleukin-8 - immunology Leukocyte Count Leukocyte Elastase - analysis Leukocyte Elastase - drug effects Male Medical sciences Middle Aged Nitriles Pharmacology. Drug treatments Phosphodiesterase Inhibitors - immunology Phosphodiesterase Inhibitors - therapeutic use Pulmonary Disease, Chronic Obstructive - drug therapy Pulmonary Disease, Chronic Obstructive - immunology Pulmonary Disease, Chronic Obstructive - physiopathology Respiratory system Sputum - chemistry Sputum - cytology Treatment Outcome |
| title | Antiinflammatory Effects of the Phosphodiesterase-4 Inhibitor Cilomilast (Ariflo) in Chronic Obstructive Pulmonary Disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T18%3A19%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Antiinflammatory%20Effects%20of%20the%20Phosphodiesterase-4%20Inhibitor%20Cilomilast%20(Ariflo)%20in%20Chronic%20Obstructive%20Pulmonary%20Disease&rft.jtitle=American%20journal%20of%20respiratory%20and%20critical%20care%20medicine&rft.au=Gamble,%20Elizabeth&rft.date=2003-10-15&rft.volume=168&rft.issue=8&rft.spage=976&rft.epage=982&rft.pages=976-982&rft.issn=1073-449X&rft.eissn=1535-4970&rft_id=info:doi/10.1164/rccm.200212-1490OC&rft_dat=%3Cproquest_cross%3E443663191%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=199558442&rft_id=info:pmid/12816740&rfr_iscdi=true |