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Protective effect of oral terfenadine and not inhaled ipratropium on adenosine 5′‐monophosphate‐induced bronchoconstriction in patients with COPD
Author(s) -
Rutgers,
Koëter,
Van Der Mark,
Postma
Publication year - 1999
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1999.00650.x
Subject(s) - bronchoconstriction , ipratropium bromide , terfenadine , ipratropium , medicine , bronchodilator , anesthesia , histamine , copd , placebo , crossover study , pharmacology , asthma , endocrinology , alternative medicine , pathology
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, FEV 1 61 ± 12% of predicted and FEV 1 /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 μg 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.