The Role of Airway Neurons in Childhood Asthma

Key Words: Asthma, Vagus nerve, Sensory, Allergic disease, Airway hyperreactivity

Asthma is a chronic disease of the airways affecting nearly 1 in 13 Americans. Symptoms of asthma are caused by narrowing of the airways and include trouble breathing, wheezing, coughing, and chest pain. The impact of asthma can be particularly devastating for children, as they have heightened susceptibility to environmental exposures, and can have life-long consequences for respiratory health. If left untreated, asthma may be fatal or lead to permanent damage of airway structures. While many factors contribute to the development of childhood asthma, including genetics, infection, allergies and environment, the causes are not fully understood. Currently there is no cure for asthma.

The nervous system has long been suspected to play a role in the development of asthma but this has been difficult to test directly. Many common asthma triggers like tobacco smoke, cold air or allergens stimulate airway neurons, which in turn control lung smooth muscle, mucus secretion, immune activation, and coughing reflexes. Despite this, it is unclear which neural pathways are engaged in disease contexts or whether targeting them may provide therapeutic benefit. Our research applies genetic tools, genomic strategies, and disease modeling in mice to explore the ways in which the nervous system contributes to airway disease. We ask basic questions like: how do airway-innervating neurons change when exposed to inflammation? Are these changes permanent, and if so, how are they remembered at a molecular level? Can activating neurons in the absence of inflammation cause features of asthma? The answers to these questions are central to understanding the steps that lead to childhood asthma. Our goal is to leverage these insights to improve airway health and design better therapies to halt or reverse the progression of chronic allergic disease.