Background

We have previously demonstrated that measuring maximum evoked coughs at any given dose (Emax) using hypotonic saline challenge discriminates refractory and unexplained chronic cough (RUCC) from healthy volunteers (HV). We further evaluated hypotonic challenge, exploring how cough responses correlate with other measures of RUCC.

Methods 

Adult RUCC and HV underwent cough challenge, with 4 single breath inhalations of descending osmolarity (300,250,200,150 and 100 mOsm/kg). Number of coughs in 15s after each inhalation were recorded. We also measured cough visual analogue scores (VAS), cough QOL (CQLQ), challenge VAS (Urge-To-Cough, taste, tickle, and irritation) and 24hr cough frequency. 

Results

50 RUCC were compared with 20 HV?s. Asthmatics and current smokers were excluded. Age, BMI and lung function were comparable.  There was a significant difference in median (IQR) Emax in RUCC 11 (3-24) compared to HV 0 (0-3), p <0.01. In RUCC, Emax was higher in females 16 (6-27) than males 5 (0-11),p = 0.01. GEE modelling, showed VAS UTC, irritation and tickle to be significantly higher across all doses in RUCC compared to HV (p<0.01), but not taste (p=0.11). There was a moderate correlation between day cough frequency/hr and Emax, Spearman?s R=0.48 (p< 0.01), compared to CQLQ R=0.14 (p = 0.34) and day VAS R=0.22 (p=0.13).

Conclusion

Hypotonic solutions activate airway nerves via a TRPV4-ATP-P2X3 axis in animal models and in humans evoke coughing in RUCC but not HV. Consistent with this mechanism driving spontaneous coughing in RUCC, we observed stronger correlations between hypotonic cough responses and objective cough frequency than with patient reported cough severity and impact.