Numerous epidemiologic studies have identified an association between occupational exposures to organophosphorus pesticides (OPs) and
asthma or asthmatic symptoms in adults. Emerging epidemiologic data suggest that environmentally relevant levels of OPs may also be linked to respiratory dysfunction in the general population and that in utero and/or early life exposures to environmental OPs may increase risk for childhood
asthma. In support of a causal link between OPs and
asthma, experimental evidence demonstrates that occupationally and environmentally relevant OP exposures induce
bronchospasm and airway hyperreactivity in preclinical models. Mechanistic studies have identified blockade of autoinhibitory
M2 muscarinic receptors on parasympathetic nerves that innervate airway smooth muscle as one mechanism by which OPs induce airway hyperreactivity, but significant questions remain regarding the mechanism(s) by which OPs cause neuronal M2 receptor dysfunction and, more generally, how OPs cause persistent
asthma, especially after developmental exposures. The goals of this review are to 1) summarize current understanding of OPs in
asthma; 2) discuss mechanisms of OP neurotoxicity and immunotoxicity that warrant consideration in the context of OP-induced airway hyperreactivity and
asthma, specifically, inflammatory responses, oxidative stress, neural plasticity, and
neurogenic inflammation; and 3) identify critical data gaps that need to be addressed in order to better protect adults and children against the harmful respiratory effects of low-level OP exposures.