Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5'-monophosphate-induced bronchoconstriction in patients with COPD.
BACKGROUND
Inhalation of adenosine 5'-monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP-induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC20AMP.


OBJECTIVE
To investigate the mechanism of AMP-induced bronchoconstriction in COPD.


METHODS
We performed a randomized, double-blind, placebo-controlled, crossover trial. Forty-four nonatopic hyperresponsive smokers with COPD (mean age +/- SD: 60+/-7 years, FEV1 61+/-12% of predicted and FEV1/VC 51+/-8%, geometric mean [GM] PC20methacholine 0.62 mg/mL and GM PC20AMP 6.77 mg/mL) participated. PC20methacholine and PC20AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 microg of inhaled ipratropium bromide, or placebo.


RESULTS
GM PC20AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P<0.0001) after terfenadine and decreasing 0.3 doubling concentration after ipratropium bromide (NS). GM PC20methacholine was 0.75 mg/mL after placebo, increasing 0.4 doubling concentration after terfenadine (NS) and 3 doubling concentrations after ipratropium bromide (P<0.0001).


CONCLUSIONS
These findings indicate that histamine release is important in the pathophysiology of AMP-induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.
Rutgers
S R
SR
Department of Pulmonology, University Hospital Groningen, Groningen, The Netherlands.
Koëter
G H
GH
Van Der Mark
T W
TW
Postma
D S
DS
D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000368:Aged; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006636:Histamine Release; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D012129:Respiratory Function Tests; D012907:Smoking; D016593:Terfenadine / Q000008:administration & dosage / Q000494:pharmacology*
D001993:Bronchodilator Agents; D006634:Histamine H1 Antagonists; D016210:Methacholine Chloride; D000249:Adenosine Monophosphate; D016593:Terfenadine; D009241:Ipratropium