COX-2 inhibition attenuates cough reflex sensitivity to inhaled capsaicin in patients with asthma.
OBJECTIVE
Cyclooxygenase (COX) is an enzyme that converts arachidonic acid to prostanoids. There are two isoforms of COX, namely COX-1 and COX-2. COX-2 is highly inducible by several stimuli and is associated with inflammation. Recent studies have shown that COX-2 is upregulated in the airway epithelium of patients with asthma but little is known about the role it plays in cough, a common symptom of bronchial asthma. This study was designed to investigate the role of COX-2 in cough reflex sensitivity in patients with asthma.


METHODS
The effect of etodolac, a potent COX-2 inhibitor, on cough response to inhaled capsaicin was examined in 17 patients with stable asthma in a randomized, placebo-controlled crossover study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting 5 or more coughs, was measured as an index of airway cough reflex sensitivity.


RESULTS
The geometric mean (geometric SEM) cough threshold was significantly increased after a 2-week treatment program with oral etodolac (200 mg twice a day) compared with placebo (36.7 [1.2] vs 21.6 [1.2] gM, P<.02).


CONCLUSIONS
These findings indicate that COX-2 may be a possible modulator augmenting airway cough reflex sensitivity in asthmatic airways.
Ishiura
Y
Y
Department of Internal Medicine, Toyama City Hospital, Toyama, Japan. ishiura-@p2322.nsk.ne.jp
Fujimura
M
M
Yamamoto
H
H
Ishiguro
T
T
Ohkura
N
N
Myou
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D002211:Capsaicin / Q000276:immunology; D003371:Cough / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2 / Q000276:immunology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D017308:Etodolac / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014797:Vital Capacity
D016861:Cyclooxygenase Inhibitors; D017308:Etodolac; D051546:Cyclooxygenase 2; D002211:Capsaicin