Effect of the leukotriene receptor antagonist pranlukast on cellular infiltration in the bronchial mucosa of patients with asthma.
BACKGROUND
It has been reported that pranlukast reduces the antigen induced immediate and late phase asthmatic responses, airway hyperreactivity to acetylcholine, and pulmonary eosinophil accumulation in guinea pigs. A study was undertaken to test the hypothesis that pranlukast may reduce the number of inflammatory cells in the bronchial mucosa of patients with asthma.


METHODS
A double blind, placebo controlled study was performed in 17 mild to moderate asthmatic subjects to examine changes in inflammatory cell infiltration in response to pranlukast (225 mg orally twice per day for four weeks). Comparisons of the mean daily beta 2 agonist use, symptom score, FEV1 percentage predicted, and airway methacholine responsiveness were made before and after treatment. Using fibreoptic bronchoscopy, bronchial biopsy specimens were obtained before and after treatment with either pranlukast (n = 10) or placebo (n = 7). Immunohistology was performed using monoclonal antibodies for CD3, CD4, CD8, CD68, NP57, AA1, EG1, EG2, gamma GTP and CD19.


RESULTS
When the pranlukast and placebo treated groups were compared there were decreases in beta 2 agonist use, symptom score, and airway methacholine responsiveness after pranlukast but no increase in FEV1 was seen. The clinical response in patients treated with pranlukast was accompanied by a reduction in CD3 (median difference -37, 95% confidence interval (CI) -69 to -1; p < 0.05), CD4 (median difference -28, 95% CI -49 to -8; p < 0.01), AA1 (median difference -15, 95% CI -26 to 0; p < 0.05) and EG2 positive cells (95% CI -35 to 0; p < 0.05), but not in EG1 positive eosinophils, gamma GTP positive cells, and CD19 positive plasma cells.


CONCLUSIONS
These results support the view that pranlukast may act by inhibition of bronchial inflammation in patients with asthma.
Nakamura
Y
Y
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Hoshino
M
M
Sim
J J
JJ
Ishii
K
K
Hosaka
K
K
Sakamoto
T
T
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D001980:Bronchi / Q000276:immunology*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents; D002867:Chromones / Q000627:therapeutic use*; D004311:Double-Blind Method; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D020024:Leukotriene Antagonists; D008297:Male; D008407:Mast Cells / Q000473:pathology; D016210:Methacholine Chloride; D009092:Mucous Membrane / Q000276:immunology; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000473:pathology
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D015703:Antigens, CD; D016085:Bronchoconstrictor Agents; D002867:Chromones; D020024:Leukotriene Antagonists; D016210:Methacholine Chloride; C047681:pranlukast