Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid.

Abstract

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(GSE 1-84) pglml) was not different from that after inhalation of procaterol (4-61 (GSE 1-84) ug/ml), which had sig- (unpublished data).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.

Atopy in cough sensitivity to capsaicin and bronchial responsiveness in young females

“…In this study, the cough threshold to inhaled capsaicin was measured as an index representing airway cough sensitivity, which was defined as the lowest concentration of capsaicin eliciting five or more coughs [2,4,6]. The reproducibility of the cough threshold was confirmed in a previous study in which the challenge was repeated at an interval of 30 min to 2 weeks in normal subjects [18,19].…”

Relationship between the acid-induced cough response and airway responsiveness and obstruction in children with asthma.

“…Judging from these observations, if an inhaled P2 agonist has any antitussive activities, it is probably due to its indirect action to change conditions in the vicinity of the cough receptors. 4 The same also applies to the protective mechanism of inhaled frusemide against various stimuli.23126 We have reported that inhaled frusemide can attenuate the acetic acid-induced cough threshold in children with asthma.717…”

Antitussive Drugs—Past, Present, and Future

“…Multiple studies have demonstrated the ability of these agents to inhibit cough, including the action of fenoterol against UNDW-induced cough (Lowry et al, , 1988a, albuterol against citric acid-induced cough , and procaterol against substance P-induced cough in volunteers with acute URTIs (Katsumata et al, 1989). However, inhaled procaterol has been shown to have no effect on cough reflex sensitivity to inhaled capsaicin in normal volunteers or in subjects with asthma or chronic bronchitis, despite inducing significant bronchodilation (Fujimura et al, 1992(Fujimura et al, , 1993. Furthermore, albuterol has been shown not to inhibit cough induced by capsaicin Smith et al, 1991) or citric acid (Pounsford et al, 1985) in normal volunteers.…”