1 / Vagal sensory neurons in chronic lung disease

BPD is a consequence of exposure to mechanical ventilation and/or high oxygen therapy provided to infants born very premature (<28 weeks gestation). Contributing to the need for these therapies is an inability to properly control breathing. Similarly, breathing control is impaired in COPD contributing to COPD exacerbations. While this is known, there exist no therapies to modulate - in a targeted manner - breathing control. Unique subpopulations of vagal sensory neurons have been shown to have distinct effects on breathing. For example, Npy2r+ vagal neurons supposedly innervate alveoli and increase breathing in anesthetized mice. Given that alveoli are reduced in BPD, is this excitatory input also reduced? We seek to define the functional role of the various vagal afferent neuronal subtypes that innervate different lung regions in the context of BPD and COPD.

2 / Pulmonary neuroendocrine cells

Pulmonary neuroendocrine cells cluster at branch points along the conducting airways as neuroepithelial bodies (NEBs). NEBs have endocrine and neuronal functions. They secrete neuropeptides that modulate airway inflammation, are responsive to hypoxia (low O2) and hypercapnia (high CO2) and are innervated by various efferent and afferent (sensory) fibers. However, the functional role of NEBs in breathing remains unknown. We hypothesize these unique airway sensors play a critical role in breathing control abnormalities in BPD and COPD given that they are hyperplastic and hypertrophied.