Pulmonary neuroendocrine cells (PNECs) represent less than 1% of airway epithelium. Aside from being precursors for small lung cancer cells, whether they play a role in normal lung function remains poorly understood. Our findings show that PNECs are essential airway sensors that perceive and respond to aerosol signals. They are essential for amplifying allergen-induced asthmatic response. When increased in number, they produce excess neuropeptides which disrupts endothelial barrier, resulting in accumulation of fluid in lung and respiratory distress. These findings illustrate the multiple facets of PNEC function in homeostasis and disease.