Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Dec 2015
ReviewEight International London Cough Symposium 2014: Cough hypersensitivity syndrome as the basis for chronic cough.
At the Eighth International London Cough Conference held in London in July 2014, the focus was on the relatively novel concept of cough hypersensitivity syndrome (CHS) as forming the basis of chronic cough. This concept has been formulated following understanding of the neuronal pathways for cough and a realisation that not all chronic cough is usually associated with a cause. The CHS is defined by troublesome coughing triggered by low level of thermal, mechanical or chemical exposure. ⋯ Tools for assessing CHS in the clinic need to be developed. New drugs may be developed to control CHS. A roadmap is suggested from the inception of the CHS concept towards the development of newer antitussives at the Symposium.
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Pulm Pharmacol Ther · Dec 2015
ReviewInteraction between TRPA1 and TRPV1: Synergy on pulmonary sensory nerves.
Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are co-expressed in vagal pulmonary C-fiber sensory nerves. Because both these ligand-gated non-selective cation channels are sensitive to a number of endogenous inflammatory mediators, it is highly probable that they can be activated simultaneously during airway inflammation. Studies were carried out to investigate whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. ⋯ This potentiating effect was absent when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, the synergism was dependent upon the extracellular Ca(2+), and the rapid onset of the action further suggests that the interaction probably occurred locally at the sites of these channels. These findings suggest that the TRPA1-TRPV1 interaction may play an important role in regulating the function and excitability of pulmonary sensory neurons during airway inflammation, but the mechanism underlying this positive interaction is not yet fully understood.
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Chronic cough is regarded as a challenging clinical problem due to its frequency and often limited therapeutic options. Chronic cough that remains refractory to usual medical treatment causes significant quality of life impairment. ⋯ Recent additions in the treatment of chronic cough have been significant as they consider cough to have a unifying diagnosis of cough hypersensitivity with or without the presence of a neuropathic basis. Effective treatments for refractory chronic cough that target these areas include behavioural treatment such as speech pathology and pharmaceutical treatment with neuromodulating medications such as gabapentin.
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Patients with chronic cough often report symptoms arising in the throat, in response to non-specific stimuli. Accordingly, the concept of a 'hypersensitivity' of the larynx in chronic cough has evolved over the past ten years. ⋯ The mechanisms underlying laryngeal hypersensitivity in chronic cough are currently unclear, however recent studies provide new clinical and physiological techniques to aid detection and monitoring of laryngeal hypersensitivity. This review provides an overview of the current state of knowledge in this field.