Background The direct effect of bronchoconstriction on cough receptor sensitivity is unknown, and the antitussive effect of 2 adrenergic agonists in man has been controversial. This study was designed to throw light on these questions. Methods The threshold of the cough response to inhaled capsaicin, a stimulant acting on C fibre endings, and tartaric acid, a chemostimulant, was measured before and 10 minutes after inhalation of methacholine, which caused a nearly 20% fall in forced expiratory volume in one second (FEV,), in 14 normal subjects (study 1), and also before and 30 minutes after inhalation of procaterol (30 jg), placebo, and saline in eight normal subjects (study 2). Progressively increasing concentrations of capsaicin and tartaric acid solutions were inhaled for 15 seconds by mouth tidal breathing at one minute intervals and cough threshold was defined as the lowest concentration of capsaicin and tartaric acid that elicited five or more coughs. Results In study 1 the geometric mean values of the cough threshold of response to capsaicin and tartaric acid before methacholine callenge, 2-98 pglml and 46-6 (1-22) mg/ml, were not significantly different from those of the response to methacholine inhalation, 3.45 pglml and 32-9 (1-37) mglml.In study 2 the geometric mean value of the cough threshold of response to capsaicin before inhalation of procaterol (4-61 (GSE 1-84) pglml) was not different from that after inhalation of procaterol (4-61 (GSE 1-84) ug/ml), which had sig- (unpublished data). This study was conducted to determine whether changes in bronchomotor tone, f2 adrenergic agonists, and muscarinic agonists influence the sensitivity of cough receptors to inhaled cough stimuli. We examined the effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on the threshold of cough in response to inhaled tartaric acid and capsaicin in normal subjects.
Methods
SUBJECTSFourteen normal 20 year old women participated in study 1 (table 1) and another eight normal women, with a mean age of 20-4 (range 20-21) years, participated in study 2. All subjects were non-smokers, had no respiratory symptoms, and had not had a viral infection for at least four weeks. Informed consent was obtained from all subjects. These studies were approved by the ethics committee of our university hospital.
MEASUREMENT OF COUGH SENSITIVITYWe determined the cough threshold as an index of cough receptor sensitivity by the method we have described previously.7 Tartaric acid (Wako Pure Chemical Industries Ltd, Tokyo) was dissolved in physiological (normal) saline to make solutions of 1-56, 3-12, 6-25, 12 5, 25, 50, 100, 200, 400 and 800 mg/ml. Capsaicin (30 5 mg) was dissolved in Tween 80 (1 ml) and ethanol (1 ml) and then in normal saline (8 ml) to make a stock solution of 3 05 mg/ml (1 x 10-2 mol/l), which was stored at -20°C.
