Modulation of cough and airway sensory fibres

It is clear that there is still no definitive answer as to the role of RARs and C-fibres in cough, although the evidence would appear to implicate both fibre types, depending on the stimulus (Fig. 2). An upregulation of the activity of these fibres during disease states, by the action of inflammatory mediators, could contribute to an enhanced cough reflex, although the possible involvement of central sensitization provides another exciting possibility. Whilst an inhibition of the activity of airway afferents should conceivably lead to an inhibition of the cough reflex there remain few examples where this occurs. The available evidence suggests that agents such as opioids and cromoglycate can act on C-fibres, contributing to their antitussive activity, whilst frusemide has an inhibitory effect, on C- and A delta-fibres, only against certain stimuli. A more generalized inhibition of airway sensory nerves could be achieved by ion channel modulators, since these might act on both myelinated and non-myelinated fibres. It is interesting that the only clear examples of an inhibition of sensory nerve activity coupled with antitussive effects are provided by sodium channel blockers (local anaesthetics) and a potassium channel opener (NS1619). However, it should be borne in mind that cough is essentially a defensive reflex, becoming inappropriate during disease states. It might be desirable therefore to inhibit only the enhanced activity of sensory nerves seen during these conditions. Whether this is possible awaits further information on the changes in sensory nerve properties during inflammation.