Cough is the most common medical condition presenting to primary care physicians. Chronic cough is defined by persistence longer than eight weeks. Chronic refractory cough that does not respond despite treatment for specific aggravating conditions or empiric treatment accounts for up to 20% of new pulmonary specialist referrals. The general scientific consensus is that such patients suffer from hypersensitivity of the airway cough receptors. However, the few available antitussive treatment options are limited by adverse effects, lack of efficacy, and abuse potential. Recent evidence has identified the key cough receptors of the human airway and has identified the specific isoform of Na-K-ATPase that modulates the sensitivity of these receptors. The divalent cation Zinc is a relatively specifi blocker of this enzyme and decreases cough sensitivity in animal models. In humans, Zinc in adequate doses has been effective in reducing cough duration after rhinovirus infections. Further, zinc has a strong safety record as a nutritional supplement and as a treatment for Wilson's disease. Accordingly, we are proposing two studies to inform the design and feasibility of a definitive trial of zinc acetate 150 mg/day (Galzin (r)) for patients with chronic refractory cough. The first study is a pilot randomized clinical trial in 36 patients treated with either placbo or 150 mg Zinc acetate daily. This trial will determine whether a definitive trial is feasible and non-futile. The second study is a panel study of 100 patients to determine the statistical and psychometric characteristics of the proposed patient-reported cough outcome measures. The trials will be conducted by the American Lung Association Airways Clinical Research Centers (ALA-ACRC) which has a long-standing successful track record for clinical trials.
Chronic refractory cough is a common condition that causes substantial impairment of quality of life and for which there are few effective treatment options. Recent laboratory evidence has found that zinc inhibits cough receptors and is a candidate treatment for patients with chronic cough. This proposal is to establish whether zinc might be effective and provide information that will inform the feasibility and design of a definitive clinial trial.