Cough induced by low pH

Respir Med. 1999 Jan;93(1):58-61. doi: 10.1016/s0954-6111(99)90078-1.


Citric acid has been used as a tussive agent in the investigation of the cough reflex. The mechanism of cough stimulation remains unclear. We conducted studies to compare the cough response of citric acid to an organic (acetic acid) and an inorganic acid (phosphoric acid). We also compared the cough response of citric acid to capsaicin, a non-acid tussive stimulus. In study 1, 26 subjects inhaled equimolar concentrations of citric and acetic acid. In study, 2, 22 subjects inhaled citric acid and phosphoric acid in concentrations of similar pH. Eighteen subjects from study 2 completed a capsaicin cough challenge test. The cough response was recorded and the concentration causing two coughs, the cough threshold, calculated (D2). The correlation of cough thresholds between both citric and acetic acid (r = 0.79, 95% CI 0.37-0.90, P < 0.0001) and citric acid and phosphoric acid (r = 0.68, 95% CI 0.37-0.86, P = 0.0005) were significant. There was no correlation between the citric acid and capsaicin cough thresholds. These results show that an individual's cough response to acetic and phosphoric acid are similar to that caused by citric acid. Thus these acids may cause cough by a common mechanism such as disturbance of the pH of the airway surface liquid. Capsaicin does not appear to share this common pathway.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acetic Acid / pharmacology
  • Acids / pharmacology*
  • Administration, Inhalation
  • Adult
  • Capsaicin / pharmacology
  • Citric Acid / pharmacology
  • Cough / chemically induced*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Middle Aged
  • Phosphoric Acids / pharmacology
  • Stimulation, Chemical


  • Acids
  • Phosphoric Acids
  • Citric Acid
  • phosphoric acid
  • Acetic Acid
  • Capsaicin