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Thus, airway remodeling promotes exacerbations in allergen-induced asthma ( The axon reflex mechanisms triggered by chemical irritants in airways stimulate the nociceptors of excitatory non-cholinergic, non-adrenergic (e-NANC) C-fiber nerve terminals innervating the airway epithelium and smooth muscle layer, which release neuropeptides such as substance P (SP), vasoactive intestinal peptide (VIP), and CGRP ( Figure 12 , the binding of SP to the neurokinin-1 receptor (NK1R) stimulates the SP/NKR-1 signaling in airway epithelial cells and ASMC, which has been implicated in inflammation and bronchoconstriction, respectively ( Figure 12 Observational studies link negative emotions in asthma patients with increased vagal cholinergic airway responses and airway hyperresponsiveness (119)
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