Effect of guaifenesin on cough reflex sensitivity

Chest. 2003 Dec;124(6):2178-81. doi: 10.1378/chest.124.6.2178.


Background: Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin.

Study objectives: To evaluate the effect of guaifenesin on cough reflex sensitivity.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Academic medical center.

Participants: Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers.

Interventions: On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo.

Measurements and results: The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers.

Conclusions: Our results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Publication types

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

MeSH terms

  • Adult
  • Capsaicin / adverse effects
  • Cough / chemically induced
  • Cough / prevention & control*
  • Double-Blind Method
  • Expectorants / therapeutic use*
  • Female
  • Guaifenesin / therapeutic use*
  • Humans
  • Male
  • Reflex / drug effects*
  • Sensitivity and Specificity


  • Expectorants
  • Guaifenesin
  • Capsaicin