Reliability of the Citric Acid Cough Reflex Test (CRT) in healthy adults

Introduction: The citric acid CRT evaluates the sensory integrity of the cough reflex. Previous studies have examined reliability of citric acid CRT. However results are not easily applied to clinical and research practices due to the use of log transformed cough thresholds and lack of standardized methods. Furthermore reliability of suppressed cough thresholds (SCT) over days is not known. This study reports variation in natural cough thresholds (NCT) and SCT when CRT is repeated across three alternate days.
Methods: Sixteen healthy participants inhaled three 1.2 s doses of increasing doubling concentrations of citric acid (0.05–3.2 mol/l) on each of 3 days. Doses were inhaled until C2 cough thresholds (2 consecutive coughs within 3 s) or the highest dose of citric acid was reached. Linear mixed effects models were used to estimate (1) the change in cough threshold (CT) per day and (2) the variability in CT across days (reported as standard deviations) for both NCT and SCT.
Results: The estimated change in CT and the variability in CT across days are shown in Table 1. An increase in both SCT (0.32 doubling concentrations per day (95% CI [0.04–0.59], p = 0.037) and NCT (0.43 doubling concentrations per day (95% CI [0.16–0.71], p = 0.005) was found. Variability for SCT was 0.77 doubling concentrations (95% CI [0.55–0.98]) and NCT was 0.78 doubling concentrations (95% CI [0.58–0.96]).
Conclusions: NCT and SCT increase across days signifying possible habituation to citric acid. Variation within participants may relate to alterations in breathing patterns or day-to-day changes in the condition of the aero digestive tract. Quantifying change as doubling concentrations facilitates integration of this data into future clinical and research studies. This is crucial to the emergence of citric acid CRT as a viable outcome measure in cough sensory research.