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document
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 . 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 .
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Intervention_Pharmacological
phosphodiesterase-4 inhibitor cilomilast ( Ariflo )
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Intervention_Pharmacological
Cilomilast ( Ariflo )
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Intervention_Pharmacological
oral phosphodiesterase-4 selective inhibitor
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Intervention_Pharmacological
cilomilast
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Intervention_Control
placebo
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Intervention_Pharmacological
cilomilast
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Intervention_Pharmacological
cilomilast
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Intervention_Pharmacological
Phosphodiesterase-4 inhibitors
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Outcome_Physical
Antiinflammatory effects
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Outcome_Physical
lung function
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Outcome_Physical
antiinflammatory effects
13260
Outcome_Physical
Induced sputum differential cell counts
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Outcome_Physical
Interleukin-8 and neutrophil elastase
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Outcome_Physical
neutrophils , CD8+ and CD4+ T-lymphocyte subsets , and CD68+ macrophages
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Outcome_Physical
genes for interleukin-8 and tumor necrosis factor-alpha
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Outcome_Physical
sputum endpoint or FEV1
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Outcome_Physical
reductions in CD8+
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Outcome_Physical
CD68+ cells
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Outcome_Physical
reductions of CD8+
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Outcome_Physical
CD68+
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Outcome_Physical
airway tissue inflammatory cells
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Participant_Condition
chronic obstructive pulmonary disease
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Participant_Sample-size
59
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Participant_Condition
COPD