Increased parasympathetic tone as the underlying cause of asthma: a hypothesis

Asthma is a chronic inflammatory disease of airways that is characterized by increased responsiveness of the tracheo-bronchial tree to multiple number of stimuli. Immunological theory does not explain all features in asthma, for example hyper-reactivity of the airways. Neurogenic theory also fails to explain the pathogenesis of asthma comprehensively. Higher parasympathetic tone has been reported in asthmatics but has never been suggested as a major underlying cause of asthma. This article attempts to explain the occurrence of hyper-responsiveness, inflammatory/allergic reactions and broncho-constriction in asthma on a common basis of inherent higher parasympathetic tone in asthmatics. The higher background parasympathetic firing leads to increased nitric oxide (NO) production owing to its co-localization with acetylcholine (ACh) in inhibitory non-adrenergic and non-cholinergic (i-NANC) nerves. NO is a neurotransmitter of i-NANC system and it mediates bronchodilation. Increased NO release has been found to be responsible for hyper-responsiveness and increased inflammation in the airways. The authors suggest that an inherently higher background parasympathetic tone in concert with inflammation or a specific genetic background could modify the effects of NO on lung homeostasis in humans leading to increased susceptibility to an asthmatic state.