Effect of cyclodextrin on sensory nerve activity and the cough reflex in man: a novel anti-tussive therapy?

Cough is a reflex mechanism that helps clear foreign material and secretions from the airways. However, it may also be the first and most persistent symptom of many inflammatory airways diseases, including, asthma, COPD, post viral infections, pulmonary fibrosis and bronchiectasis. Chronic cough can also be present when a cause can not be identified. At present there are no effective treatments for this condition. Therefore, the identification of new drugs for the treatment of chronic cough will be of immense benefit and will greatly enhance the quality of life of many patients and sufferers. The reflex action of coughing is initiated when sensory nerves in the airway are activated. Our research looks into whether agents which prevent the sensory nerves in the airway from being activated, will also inhibit the cough reflex. This project in particular looks at cyclodextrin as a possible agent. Previous pre-clinical studies have demonstrated the inhibitory effects of cyclodextrin in preventing cough. This project seeks to take this work further and to test the inhibitory activity of cyclodextrins on the cough reflex in man.

Cough is an important defense mechanism that helps clear excessive secretions and foreign material from the airways. However, it also presents as the first and most persistent symptom of many inflammatory airways diseases, including asthma, COPD, post viral infections, pulmonary fibrosis and bronchiectasis. Chronic cough can also be idiopathic in nature. To date, the only effective treatments for cough are opioids which have central and peripheral side effects. Therefore, the identification of novel therapeutic targets for the treatment of chronic cough will be of immense therapeutic benefit and will greatly enhance the quality of life of patients. The cough reflex is initiated by activation of airway sensory afferent nerves. We hypothesize that agents that inhibit sensory nerve activity will also inhibit the cough reflex. In this proposal we describe pre-clinical data demonstrating the anti-tussive activity of cyclodextrins both in vitro on sensory nerve function and in vivo in a guinea-pig cough model. The aim of this proposal is to test the anti-tussive activity of this molecule in man and to investigate the possible mechanism of action.