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Abstract: The mammalian transient receptor potential (TRP) superfamily of cation channels is divided into six subfamilies based on sequence homology TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPP (polycystin) and TRPML (mucolipin). The expression of these channels is especially abundant in sensory nerves, and there is increasing evidence demonstrating their existence in a broad range of cell types which are thought to play a key role in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). These ion channels can be activated by a diverse range of chemical and physical stimuli. Physical stimuli include temperature, membrane potential changes and osmotic stress, and some of the more well known chemical stimuli include capsaicin (TRPV1), menthol (TRPM8) and acrolein (TRPA1). There is increasing evidence in this rapidly moving field to suggest that selective blockers of these channels may represent attractive novel strategies to treat characteristic features of respiratory diseases such as asthma and COPD. This review focuses on summarising the evidence that modulation of selected TRP channels may have beneficial effects at targeting key features of these respiratory diseases including airways inflammation, airways hyper-reactivity, mucus secretion and cough. [Copyright &y& Elsevier]

Abstract: To cough is a protective defence mechanism that is vital to remove foreign material and secretions from the airways and which in the normal state serves its function appropriately. Modulation of the cough reflex pathway in disease can lead to inappropriate chronic coughing and an augmented cough response. Chronic cough is a symptom that can present in conjunction with a number of diseases including chronic obstructive pulmonary disease (COPD) and asthma, although often the cause of chronic cough may be unknown. As current treatments for cough have proved to exhibit little efficacy and are largely ineffective, there is a need to develop novel, efficacious and safe antitussive therapies. The underlying mechanisms of the cough reflex are complex and involve a network of events, which are not fully understood. It is accepted that the cough reflex is initiated following activation of airway sensory nerves. Therefore, in the hope of identifying novel antitussives, much research has focused on understanding the neural mechanisms of cough provocation. Experimentally this has been undertaken using chemical or mechanical tussive stimuli in conjunction with animal models of cough and clinical cough assessments. This review will discuss the neural mechanisms involved in the cough, changes that occur under pathophysiological conditions and and how current research may lead to novel therapeutic opportunities for the treatment of cough. [Copyright &y& Elsevier]