Adaptation of cough reflex with different types of stimulation

The recent paper in this journal by MoRICE et al. [1] lends considerable insight into the different mechanisms of adaptation of the cough response to citric acid (CA), nebulised distilled water (NDW) and capsaicin. The relative absence of tachyphylaxis with continuous tidal breathing of capsaicin over 1 minute tends to corroborate previous reports that capsaicin is predominantly a stimulant of unmyelinated C-fibres which adapt slowly, while NDW and CA stimulate rapidly-adapting myelinated fibres. The observation that significant tachyphylaxis occurs with repeated inhalation of capsaicin at 10 minute intervals for 40 minutes is consistent with data which we have recently collected in 18 subjects. We constructed concentration-response curves by administering single breaths (0.008 mls·breath'1) of doubling concentrations of capsaicin from 0.5-500 !lM at 1 minute intervals from a breath-activated nebulizer/ dosimeter. The number of coughs in the 1 minute period following each breath was recorded and the challenge stopped when the lowest concentration which elicited 5 or more coughs (CS) had been administered. Fifteen minutes later we administered 2 breaths of CS (30 seconds apart) at 0, 1, 3, S, 10, 20, 30 and 60 minutes. The number of coughs in response to either of the 2 breaths at 0 minutes (baseline) was not significantly different to the response to CS from the initial concentration-response challenge (mean±SEM coughs in response to 2 breaths at baseline = 9.9±0.26). The cough response at 1 minute (9.1±0.54) was similar to the baseline response which is consistent with the observation of Morice et al. that minimal tachyphylaxis occurs over this period. The response at all subsequent time points was significantly less than baseline however (p<0.001), reaching its lowest at 5 minutes (7.6±0.38). The response had almost recovered at 60 minutes (8.5±0.41). These data confirm the observation of Morice et al. that tachyphylaxis of the cough response to capsaicin occurs with repeated inhalation over 40 minutes. However, we have also performed capsaicin challenges (to construct concentration-response curves as outlined above) at 0 (baseline), 1 and 2 hours in 16 subjects and at 0, 1 and 4 hours in 23 subjects and in these studies there was no significant difference in log CS (or log C2, the lowest concentration which elicits 2 or more coughs) between the baseline and subsequent challenges (table 1). Significant tachyphylaxis therefore does not occur when capsaicin challenge is repeated at intervals of 1 and 3 hours. This is at variance with the data of Morice et al. although the methods used in the two studies were different. In addition we have performed capsaicin challenges as outlined above at an average interval of 7 days (5-10 days) at the same time on each day in 40 subjects. There was no significant difference between the two challenges for either log C2 or log CS. The difference between the two challenges (number of doubling dilutions) for C2 and CS were 0 .85±0.15 and 0.93±0.16 respectively, indicating that the results of challenge were highly repeatable. In the study of Morice et al. capsaicin challenge was also highly repeatable at 1 week.