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.
journal_name
Am J Respir Crit Care Medauthors
Gamble E,Grootendorst DC,Brightling CE,Troy S,Qiu Y,Zhu J,Parker D,Matin D,Majumdar S,Vignola AM,Kroegel C,Morell F,Hansel TT,Rennard SI,Compton C,Amit O,Tat T,Edelson J,Pavord ID,Rabe KF,Barnes NC,Jeffery PKdoi
10.1164/rccm.200212-1490OCkeywords:
subject
Has Abstractpub_date
2003-10-15 00:00:00pages
976-82issue
8eissn
1073-449Xissn
1535-4970pii
200212-1490OCjournal_volume
168pub_type
临床试验,杂志文章,随机对照试验abstract::Although abnormalities of alveolar fibrin turnover have been reported to play a role in the development of idiopathic pulmonary fibrosis (IPF), the pathophysiological relevance remains unclear. We therefore investigated the localization of tissue factor (TF) and fibrin deposition in patients with IPF using immunohisto...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.2.9608094
更新日期:1997-08-01 00:00:00
abstract:RATIONALE:The molecular mechanisms underlying acute exacerbations of idiopathic pulmonary fibrosis (IPF) are poorly understood. We studied the global gene expression signature of acute exacerbations of IPF. OBJECTIVES:To understand the gene expression patterns of acute exacerbations of IPF. METHODS:RNA was extracted ...
journal_title:American journal of respiratory and critical care medicine
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pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.201302-0264OC
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.2.9906015
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更新日期:1995-08-01 00:00:00
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更新日期:2008-01-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:1996-09-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2003-08-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2013-09-15 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1995-12-01 00:00:00
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更新日期:2004-04-15 00:00:00
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abstract::Stenotrophomonas maltophilia is a gram-negative bacterium that has been cultured with increasing prevalence from the sputum of patients with cystic fibrosis (CF). We conducted a cohort study, using the Cystic Fibrosis Foundation Registry, to assess the effect of S. maltophilia on survival. We studied all patients in t...
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journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2002-11-01 00:00:00