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

Clin Exp Allergy. 1999 Sep;29(9):1287-92. doi: 10.1046/j.1365-2222.1999.00650.x.


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).

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / pharmacology*
  • Aged
  • Bronchoconstriction / drug effects*
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / pharmacology
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Histamine H1 Antagonists / administration & dosage
  • Histamine H1 Antagonists / pharmacology*
  • Histamine Release
  • Humans
  • Ipratropium / administration & dosage
  • Ipratropium / pharmacology
  • Lung Diseases, Obstructive / physiopathology*
  • Male
  • Methacholine Chloride / pharmacology
  • Middle Aged
  • Respiratory Function Tests
  • Smoking
  • Terfenadine / administration & dosage
  • Terfenadine / pharmacology*


  • Bronchodilator Agents
  • Histamine H1 Antagonists
  • Methacholine Chloride
  • Adenosine Monophosphate
  • Terfenadine
  • Ipratropium