Clinical & Experimental Allergy

Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5′-monophosphate-induced bronchoconstriction in patients with COPD

Authors


Postma Department of Pulmonology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.

Abstract

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 μg 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).

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, PC20AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.

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