One of the most elusive challenges in the diagnosis and treatment of dysphagia is the reliable identification of silent aspiration (aspiration in the absence of cough). The citric acid inhalation cough challenge offers potential for aiding in identification of silent aspiration; however clinical application of this technique is currently problematic due to an absence of normative data. Therefore, this study aimed to establish a normative data set for the Citric- Acid Inhalation Cough Challenge, as administered with facemask method. 80 healthy subjects will participate in this study, constituting 2 age groups: above and below 60 years, with equal gender representation. On 3 separate trials, they will be asked to passively inhale, via a facemask, nebulised citric acid of concentrations ranging from 08M to 2.6M with placebo interspersed. ‘Natural cough thresholds’ (NCT) and ‘Suppressed Cough Thresholds’ (SCT) will be reached when subjects cough on at least 2 out of 3 trials. The majority (92.5%) of participants reached Natural Cough Threshold by 0.8M, with 68% demonstrating Suppressed Cough Threshold also at this concentration. There were no significant differences found between males and females (p<0.05) for either NCT (p=0.9885) or SCT (p=0.44). Whilst no difference was found between youngers and elders for NCT (p=0.7254), there was a significant difference for SCT (p=0.018), with youngers better able to suppress cough. Over 90% of healthy people were found to elicit cough at 0.8M, inferring that this level would be an adequate guide for use by clinicians testing for presence/absence of cough.

Introduction: Cough is the commonest reason for which medical advice is sought. In assessment of chronic cough and in developing anti-tussive medications, inhalational cough challenges with capsaicin and citric acid are commonly employed. However the ability of these inhalational cough challenges to distinguish health and disease is not clear and it is not known which end point is best in making such assessments. Methods: Subjects belonging to five different categories (healthy volunteers, subjects with COPD, asthma, healthy current smokers and chronic cough) were compared with each another by using the standard cough challenges employing Capsaicin and Citric acid and also by using newer inhalational cough challenge agents such as prostaglandin E2 and bradykinin. In addition adaptation to repeated inhalations of tussive agents was also assessed. The relationship between the cough reflex sensitivity as gauged by using inhalational cough challenge tests and objective cough recording was explored in all five groups. Finally the change in C5 in Capsaicin evoked cough by using a substance to block TRPV1 channel and its effect on objective cough recording was assessed in subjects with chronic cough. Results: Different tussive agents have different abilities to distinguish between different diagnostic categories and a combination of inhalational cough challenge tests have a better accuracy of predicting diagnostic groups as compared to one on its own. There are significant differences in the rates of adaptation to repeated inhalations of PGE2 and there is a significant reduction in cough response over period of time in all disease groups. Using the TRPV1 antagonist resulted in a modest increase in the Log C5 concentration of capsaicin but this was not matched by a change in objective cough recording or CQLQ scores. Conclusions: The different abilities of tussive agents to distinguish between different diagnostic categories suggest that the information conveyed by the one inhalational cough challenge test is different from that by another test. The choice of the inhalational cough challenge test should therefore depend on which groups are included in the study. There was no significant difference in the rate of adaptation to prolonged challenge with citric acid or capsaicin and no significant correlation of the magnitude of adaptation with objective cough recording suggesting that this is unlikely to be responsible for the increased cough rates seen in diseases such as chronic cough, COPD or asthma. The TRPV1 antagonist did not result in a significant change in objective cough recording or CQLQ scores. The change in C5 with the TRPV1 antagonist was however modest and this may be reason for this study failing to show a relationship between these different measures.