Background: The hydration status of surface liquid in the larynx and trachea may regulate peripheral cough receptors.

Hypothesis: Topical hypertonic divalent salts (HDS) buffered to alkalinity provides relief for refractory chronic cough.

Methods: We conducted an exploratory, single-blinded controlled study in 12 chronic cough patients to examine cough-suppression efficacy of a nasally delivered HDS composition (SC001) at pH 8 or pH 9, compared to a normal saline (NS) control. Subjects were monitored continuously using the HYFE digital cough watch for one week of baseline, one week of NS, and one week of SC001.

Results: Baseline cough rates ranged from 4 to 41 coughs/hr with a mean visual analog score (VAS) of 65±17.  Adjusting for control, SC001 demonstrated efficacy at suppressing cough by 15% from Day 1 (p=0.015) and 23% from Day 3 (p=0.002) overall (n=12). Efficacy was highest in subjects treated with SC001 pH 9 (n=5), with a 25% cough-suppression observed from Day 1 (p=0.03) and 35% from Day 3 (p=0.02). Lower efficacy was observed for SC001 pH 8 (n=7), with 9% (p=0.08) and 16% (p=0.02) suppression observed from Day 1 and Day 3 respectively. Hourly cough counts correlated with VAS scores (? = 0.266, p-value = 0.015) at baseline and increased with treatment (? = 0.507, p-value = 0.000002). No adverse events were reported.

Conclusions: Alkaline (pH 9) HDS aerosol is a promising treatment for refractory chronic cough.