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

[No Value] Rutgers, GH Koeter, TW Van der Mark, DS Postma*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

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 (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

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.

Original languageEnglish
Pages (from-to)1287-1292
Number of pages6
JournalClinical and Experimental Allergy
Volume29
Issue number9
Publication statusPublished - Sep-1999

Keywords

  • adenosine 5 '-monophosphate (AMP)
  • COPD
  • histamine
  • hyperresponsiveness
  • ipratropium bromide
  • methacholine
  • smoking
  • terfenadine
  • OBSTRUCTIVE PULMONARY-DISEASE
  • CHRONIC-BRONCHITIS
  • MAST-CELLS
  • ASTHMA
  • HISTAMINE
  • AIRWAYS
  • METHACHOLINE
  • INFLAMMATION
  • MACROPHAGES
  • COMBINATION

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