Effect of a phosphodiesterase 3 inhibitor, cilostazol, on bronchial hyperresponsiveness in elderly patients with asthma.
BACKGROUND
Over the last few years, evidence has accumulated that cyclic nucleotide phosphodiesterase (PDE) 3 and/or PDE4 inhibitors may be useful for the treatment of asthma. The present study was designed to examine the effect of a selective orally active PDE3 inhibitor, cilostazol, on bronchial hyperresponsiveness (BHR) of asthma.


METHODS
The effect of a single oral dose of cilostazol on BHR was studied in 10 elderly patients with clinically stable asthma, with a mean age of 59.5+/-4.8 years, in a double-blind, crossover, placebo-controlled study. Each subject received 100 mg of cilostazol, 200 mg of theophylline as a positive control or a placebo in a random order. The subjects underwent a methacholine challenge test 3 h after each drug administration on three occasions separated by 2 weeks.


RESULTS
The geometric mean value of the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20-FEV1) with cilostazol was 0.48 mg/ml [geometric standard error of the mean (GSEM), 1.40] which was significantly (p<0.01) greater than that with the placebo [0.25 mg/ml (GSEM, 1.36)]. The value with theophylline [0.32 mg/ml (GSEM, 1.54)] did not differ significantly from that with cilostazol or the placebo. Baseline forced vital capacity (FVC) and FEV1 values significantly (p<0.05 and p<0.001, respectively) increased with cilostazol from 2.73+/-0.25 and 1.52+/-0.17 to 2.86+/-0.23 and 1.65+/-0.17 liters, respectively. Theophylline did not significantly increase the FVC or FEV1 value.


CONCLUSIONS
It is suggested that the PDE3 inhibitor, cilostazol, has bronchodilator and bronchoprotective effects in elderly asthmatics.
Fujimura
M
M
Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Kamio
Y
Y
Myou
S
S
Hashimoto
T
T
Matsuda
T
T
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D000077407:Cilostazol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013806:Theophylline / Q000627:therapeutic use
D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol