Variability and trial effect of tidal-breath dose-response citric acid cough reflex tests
Thesis DisciplineSpeech and Language Sciences
Degree GrantorUniversity of Canterbury
Degree NameMaster of Science
Introduction: A reproducible method is crucial in establishing cough sensitivity. Although reproducibility of the tidal-breath dose-response (TB-DR) method using capsaicin has been validated; the same method using citric acid is uninvestigated. This study determined the variability across multiple cough reflex tests (CRT) of suppressed cough thresholds in healthy individuals. Materials & Methods: Sixteen healthy volunteers underwent five CRTs (inter-test interval of at least 30 mins) within a single day. The TB-DR method was used to administer progressively increasing 0.1 mol/L increments of citric acid, ranging from 0.1-1.6 mol/L. Up to three 15-second trials of each concentration (45-second inter-trials interval) were administered via facemask. Placebo trials of saline were randomly interspersed. The suppressed cough threshold was defined as the lowest concentration producing two consecutive coughs on 2/3 trials. Data were analysed using a linear mixed effects model. The 95% prediction interval for within-participant variability was derived from the model using a bootstrapping method. Results: The fixed effect results revealed that the mean SCT at baseline test across participants (model intercept) was 0.29 mol/L, 95% bootstrapped CI [0.12, 0.45]. The effect of test on SCT was 0.003 mol/L, 95% bootstrapped CI [-0.02, 0.03]. For the random effects, the variability due to participants at baseline SCT was 0.33 mol/L, 95% bootstrapped CI [0.21, 0.45]. The variability of the CRT effect between participants was 0.04 mol/L, 95% bootstrapped CI [0.02, 0.06] while the variability for the residuals (within participant variability) was 0.08 mol/L, 95% bootstrapped CI [0.06, 0.09]. The 95% prediction interval for the residuals (variability within a participant) was [-0.14mol/L, 0.16 mol/L]. Conclusions: This study defined the variability of citric acid CRT using the TB-DR method. There was no systematic trend in responses observed over the course of five CRTs. However, the high percentage of variability for baseline SCT between participants suggests caution in establishing normative thresholds. The fairly consistent within-participant measures suggest CRT may be useful for repeated measures in tracking change as treatment effect within an individual participant or patient.