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 (H-1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC(20)AMP. 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] PC(20)methacholine 0.62 mg/mL and GM PC(20)AMP 6.77 mg/mL) participated. PC(20)methacholine and PC(20)AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 mu g of inhaled ipratropium bromide, or placebo. Results GM PC(20)AMP 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 PC(20)methacholine 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). Conclusion 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, PC(20)AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.