Purpose: Citric acid cough reflex testing (CRT) has been used within the clinical swallowing examination to evaluate laryngeal sensation and infer silent aspiration risk. Cough thresholds are defined solely by the concentration of citric acid that evokes coughing. Coughing is evoked by reduction in pH levels in the laryngeal environment, which occurs with higher doses of the same citric acid concentrations, suggesting that the amount of citric acid might be important to factor into threshold definitions. Furthermore, citric acid doses vary across CRT protocols, depending on factors such as the nebuliser and dosimeter used, differences in number of discrete inhalations across protocols, individual variation in respiratory patterns during tidal breathing. This study investigates the effect of citric acid dosage on evoked cough response.

Methods: 16 healthy participants (23-79 years, eight men) attended two sessions spaced exactly a week apart. Citric acid doses of 0.1 to 1.9mol/L were inhaled in 0.2mol/L increments via a mouthpiece attached to a jet nebuliser and dosimeter. Each concentration of acid was inhaled once for the protocol of one session and six times for the protocol of the other session for a six-fold dosage. Both protocols included an initial saline practice dose and four placebo doses at regular intervals. A three-minute break and mandatory sip of water were taken after each step of the protocols. Natural cough threshold (NCT) across two cough threshold definitions (i.e. first C2 and consistent C2) and UTC at these cough thresholds were measured. A paired t-test for first C2 and a permutation t-test for consistent C2 were used to compare results across both protocols.

Results: Cough thresholds were higher in the one-inhalation than the six-inhalation protocol for first C2 (mean difference 0.36mol/L, 95% CI [0.09, 0.63], p = 0.01) and consistent C2 (mean difference 0.55mol/L, 95% CI [0.09, 1], p = 0.02). Participants also displayed other airway protection behaviours throughout both protocols e.g. swallows, throat clears, change of respiratory patterns. There was no difference in UTC rating at cough threshold for first C2 (p = 0.49) and consistent C2 (p = 0.24) across both protocols.

Conclusion: Airway sensitivity was increased with more inhalations of the same concentrations of citric acid. This implies that dosage may influence cough response when aspects of respiration are not controlled. This highlights that current definitions of cough threshold are insufficient to accurately indicate airway sensitivity, signifying the need to include both parameters of concentration and dosage. Until then, comparison of results from CRT protocols that differ in citric acid dosage delivered needs to be made with caution.