Figure 1: Two distinct vagal parasympathetic pathways regulate airway tone. Cholinergic preganglionic neurons originate in the brainstem and provide cholinergic drive to airway autonomic ganglia. Cholinergic postganglionic neurons are the major contractile input to the airways, whereas noncholinergic neurons expressing nitric oxide and vasoactive intestinal peptide provide the relaxant innervation to the airways. Airway sensory nerves contribute differential reflex regulation over cholinergic and non-cholinergic vagal pathways at the level of the brainstem and/or the airway ganglia. Dysfunction in ganglionic neurotransmission, neuromuscular transmission, or sensory reflexive control will precipitate changes in airway smooth muscle reactivity.