Targeting TRP channels in airway disorders

Abstract

Novel effective therapeutic agents are actively sought for the treatment of a broad spectrum of respiratory diseases which collectively significantly impact on mortality, morbidity and quality of life of hundreds of millions of people world-wide. These include asthma, allergic rhinitis, chronic obstructive pulmonary disease, cough, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, cystic fibrosis and acute lung injury. TRP channels are broadly distributed throughout the respiratory tract and play an important physiological role in sensing and subsequently responding to a wide variety of stimuli, for example temperature, osmolarity and oxidant stress. In the context of respiratory disease however TRP channel function may be altered, eg: under conditions of oxidative stress, inflammation, hypoxia and mechanical stress. In addition there is evidence that the expression/activity of TRP channels can be affected in the disease setting. Modulators of TRP channel function are therefore under investigation for a range of diseases including disorders of the respiratory system. Several excellent review articles have discussed in detail evidence that modulation of specific TRP channels may be of benefit in specific respiratory diseases. In this article we have taken the approach of reviewing evidence that modulation of TRP channel function may be able to affect common and over-lapping characteristic features of respiratory diseases, for example bronchoconstriction, airways hyper-responsiveness, cough, airways inflammation, mucus hyper-secretion, exacerbations, lung injury, hypoxia and airways re-modelling. The therapeutic potential of TRP channel modulators, the status of these agents in the clinic along with the challenges posed in this rapidly advancing field are also discussed in this review.