ABSTRACT Xiaojia Wang. CIRCADIAN ACTIVATION OF MAST CELLS MEDIATES THE

Circadian rhythm is a conserved physiological feature of most organisms. Nocturnal symptoms are a common feature of allergic asthma in humans. Patients with nocturnal asthma show circadian variation of their pulmonary function and inflammation, but nocturnal asthmatic responses have not been documented in animal models. In this study we tested the hypotheses that house dust mite (HDM) allergen-sensitive nonhuman primates (NHP) manifest nocturnal symptoms, and whether intrinsic circadian activity in mast cells might underlie nocturnal asthma response. Dynamic compliance (Cdyn) and lung resistance (RL) measured as indicators of bronchoconstriction in anesthetized NHP, at rest and following exposure to HDM allergen, methacholine, and albuterol, were highly correlated with 3 respiratory inductive plethysmography (RIP) parameters: Phase Angle of the rib cage and abdomen waveforms (PhAng), Baseline Effort Phase Relation (eBPRL) and Effort Phase Relation (ePhRL). 21 allergic subjects were challenged with HDM early in the morning, and eBPRL and ePhRL were monitored for 20 hours after provocation. 15 of the allergic subjects exhibited gradual increases in eBPRL and ePhRL between midnight and 6 AM