Interpretation of positive results of a methacholine inhalation challenge and 1 week of inhaled bronchodilator use in diagnosing and treating cough-variant asthma

Arch Intern Med. 1997 Sep 22;157(17):1981-7.


Background: In diagnosing cough due to asthma, methacholine chloride inhalation challenge (MIC) interpreted in a traditional fashion has been shown to have positive predictive values from 60% to 82%.

Objective: To determine whether any features of positive results of an MIC or the results of a 1-week trial of inhaled beta-agonist therapy were helpful in predicting when the cough was due to asthma.

Methods: The study design was a prospective, randomized, double-blind, placebo-controlled, crossover format performed in adult, nonsmoking subjects, who were referred for diagnosis and treatment of chronic cough. The subjects had no other respiratory complaints or medical conditions for which they were taking medications, the results of baseline spirometry and chest roentgenograms were normal, and the results of MIC were positive. After obtaining baseline data, including MICs on 2 separate days, objective cough counting, and self-assessment of cough severity using a visual analog scale, subjects were randomized to receive 2 inhalations (1.3 mg) of metaproterenol sulfate or placebo by metered dose inhaler attached to a spacer device every 4 hours while awake. At 1 week, data identical to baseline were collected, and subjects received the other metered dose inhaler for 7 days. At 1 week, data identical to baseline were collected. After completion of the protocol, subjects were followed up in the clinic to observe the final response of the cough to specific therapy.

Results: Based on the disappearance of the cough with specific therapy, the cough was due to asthma in 9 of 15 subjects and nonasthma in 6 of 15 subjects. Baseline data were similar between groups. With respect to MICs, there were no significant differences between groups in the cumulative dose of methacholine that provoked a 20% decrease in forced expiratory volume in 1 second from the postsaline baseline value (PD20 values), slopes of dose-response curves, and maximal-response plateaus. Cough severity significantly improved after 1 week of metaproterenol use compared with the severity of the cough at baseline (P = .03) and with placebo (P = .02) only in subjects with asthma.

Conclusions: No matter how the results are analyzed, positive MIC results, without observing response to therapy, are only consistent with asthma as the cause of the cough. The results are only diagnostic of asthma when they are followed by a favorable response to asthma therapy. After 1 week of inhaled beta-agonist, only the cough due to cough-variant asthma is significantly better.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / administration & dosage*
  • Adult
  • Aged
  • Asthma / complications
  • Asthma / diagnosis*
  • Asthma / drug therapy*
  • Bronchial Provocation Tests* / methods
  • Bronchial Provocation Tests* / statistics & numerical data
  • Bronchoconstrictor Agents* / administration & dosage
  • Bronchodilator Agents / administration & dosage*
  • Cough / diagnosis*
  • Cough / drug therapy*
  • Cough / etiology
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Metaproterenol / administration & dosage*
  • Methacholine Chloride* / administration & dosage
  • Middle Aged
  • Prospective Studies
  • Time Factors


  • Adrenergic beta-Agonists
  • Bronchoconstrictor Agents
  • Bronchodilator Agents
  • Methacholine Chloride
  • Metaproterenol