Capsaicin Cough Challenge Research Articles

Cough induced by low pH

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.

Comparison of the Antitussive Effects of Codeine and the GABA-Agonist Baclofen

γ-Aminobutyric acid (GABA) is an inhibitory transmitter of the central nervous system that also exists in peripheral tissues, including the lung. The GABA-agonist baclofen has been shown, in animal studies, to inhibit cough via a central mechanism. We have recently demonstrated the antitussive activity of a 14-day course of low-dose oral baclofen in normal subjects. In the present study, we evaluated a standard cough suppressant, codeine, and compared its antitussive effect with that of a single dose of baclofen. 10 healthy, adult volunteers who had previously participated in a study evaluating the antitussive effect of a 14-day course of baclofen, underwent capsaicin cough challenge on three occasions, 2 hours after the ingestion of codeine (30mg), baclofen (40mg) or placebo, which were dispensed in a randomised, double-blind manner. During each study, the concentration of capsaicin inducing 5 or more coughs (C5) was determined. Significant suppression of cough was achieved by codeine (p = 0.021). Although a single dose of baclofen demonstrated cough suppression in some individuals, its effect was not significant for the study group as a whole (p = 0.066). The change in cough threshold from baseline (Δlog C5) produced by single doses of codeine and baclofen were not significantly different (p = 0.434). In light of our previous study that demonstrated the significant antitussive effect of a 14-day course of low-dose baclofen, the inability of a single, large dose of baclofen to suppress cough in the current study suggests the need for multiple administrations to achieve the optimal inhibitory effect of this agent.

Capsaicin cough receptor sensitivity test in children.

Capsaicin has been used as a tussive agent in studies in adults to determine cough receptor sensitivity. The aim of this study was to determine the tolerance, repeatability and influence of inspiratory flow on the capsaicin cough receptor sensitivity test in children. Thirty children (mean age 11 yrs; range 6-16 yrs) were tested on two different days, to determine the lowest concentration of capsaicin required to stimulate two or more coughs (cough threshold (Cth)), 2-4 coughs (C2), and five or more coughs (C5). Capsaicin was nebulized through a dosimeter, with an arrangement that allowed the subjects to visualize and regulate their inspiratory flow. Using a constant inspiratory flow of 20 L x min(-1), tests were reproducible for C2, C5 and Cth (doubling dose changes of 1.13, 1.03 and 1.08, respectively). An increase in the inspiratory flow from 20 to 60 L x min(-1) significantly increased C2 (19.5 to 46.8 microM; p=0.016) and C5 (46.8 to 128.8 microM; p=0.008). We conclude that in children, the capsaicin cough challenge test: 1) is well-tolerated; 2) is highly repeatable; and that 3) the inspiratory flow significantly influences cough receptor sensitivity and repeatability of the test and should, thus, be regulated.

The effect of oral terfenadine on the sensitivity of the cough reflex in normal volunteers

Antihistamines have been reported to have antitussive actions in allergic rhinitis which may be due to an effect of the drug on the cough reflex. We have studied the effect on induced cough in normal volunteers. Ten volunteers inhaled capsaicin at concentrations between 0.78 and 200 μ m, in increasing dose order, until they coughed more than five times. The challenge was performed three times before and three times each at 2 and 4 h after 120 mg terfenadine or matched placebo tablet in a double-blind, randomized, cross-over study. Neither affected the capsaicin cough challenge. Thus, any antitussive effect of terfenadine is more likely to be via an indirect mechanism such as inhibition of released histamine rather than on the cough reflex itself.