Gender differences in perceptions of urge to cough and dyspnea induced by citric acid in healthy never smokers

Chest. 2010 Nov;138(5):1166-72. doi: 10.1378/chest.10-0588. Epub 2010 Sep 16.


Background: The mechanism of the gender difference in cough reflex threshold has not been clearly elucidated. In the present study, we evaluated gender differences in the cough reflex threshold along with the perceptions of respiratory sensations, urge to cough, and dyspnea.

Methods: Nineteen male and 20 female healthy never smokers were recruited through public postings. The cough reflex threshold and the urge to cough were evaluated by inhalation of citric acid. The perception of dyspnea was evaluated by Borg scores during applications of external inspiratory resistive loads.

Results: The cough reflex threshold and suprathreshold to citric acid in women, as expressed by the log transformation of the lowest concentration of citric acid that elicited two or more and five or more coughs, was significantly lower than that in men. The urge-to-cough log-log slope in women (1.47 ± 0.81 point × L/g) was significantly steeper than in men (0.96 ± 0.28 point × L/g; P < .03). There were no significant differences in the urge-to-cough threshold estimated between men and women. The slope of the dyspnea Borg score change during the external inspiratory resistive loads is steeper in women (0.17 ± 0.04 point/cm H₂O/L/s) than that in men (0.13 ± 0.05 point/cm H₂O/L/s; P < .01). The urge-to-cough slope significantly correlated with the perception of dyspnea slope (r = 0.537; P < .01).

Conclusions: The gender difference in cough reflex threshold accompanied the gender difference in amplification rate of respiratory sensations in the same direction. The higher central gain for common pathways for respiratory sensations may play a role in lower cough reflex threshold in women. Further studies are needed to elucidate this issue.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Chelating Agents / administration & dosage
  • Chelating Agents / adverse effects
  • Citric Acid / administration & dosage
  • Citric Acid / adverse effects*
  • Cough / chemically induced
  • Cough / epidemiology*
  • Cough / physiopathology
  • Dyspnea / chemically induced
  • Dyspnea / epidemiology*
  • Dyspnea / physiopathology
  • Female
  • Follow-Up Studies
  • Humans
  • Japan / epidemiology
  • Male
  • Perception / drug effects*
  • Prevalence
  • Reference Values
  • Reflex / drug effects*
  • Sex Distribution
  • Sex Factors
  • Smoking
  • Young Adult


  • Chelating Agents
  • Citric Acid