Inhaled alkaline hypertonic divalent salts reduce refractory chronic cough frequency

Treatment of chronic cough remains a challenge. We hypothesized that inhaled alkaline hypertonic divalent salts (alkaline HDS) might provide relief for refractory chronic cough by laryngeal and tracheal hydration.We conducted an exploratory, single-blinded, nasal-saline-controlled study in 12 refractory chronic cough patients to examine cough-suppression efficacy of an alkaline HDS composition (SC001) at pH 8 or pH 9 administered by nasal inhalation. As control, we used nasal saline with the same hand-held pump spray aerosol device. Each subject was monitored continuously using a digital cough monitor watch for one week of baseline, one week of control treatment, and one week of active treatment.Baseline daily cough rates ranged from 4 to 34 coughs/hour with mean visual analog score 65±17 pre- and post-baseline testing. Control-adjusted efficacy of cough rate reduction ranged from 15% (p=0.015) (from Day 1) to 23% (p=0.002) (from Day 3). Control-adjusted efficacy was highest with SC001 pH 9 (n=5), ranging from 25% (p=0.03) (from Day 1) to 35% (p=0.02) (from Day 3), and lowest for SC001 pH 8 (n=7), ranging from 9% (p=0.08) (from Day 1) to 16% (p=0.02) (from Day 3). Hourly cough counts and VAS correlated for baseline (r=0.254, p-value=0.02) and control (r=0.299, p-value=0.007) monitoring weeks. Treatment improved this correlation (r=0.434, p-value=0.00006). No adverse events were reported.Alkaline (pH 9) HDS aerosol is a promising treatment for refractory chronic cough and should be further evaluated.