The long term objective of this project is to understand the chronobiology of asthma so as to improve asthma treatment in general thereby decreasing asthma morbidity and mortality. The nocturnal worsening of asthma is associated with the three major asthma characteristics: reversible airway obstruction, bronchial hyperresponsiveness, and inflammation. These characteristics occur on a circadian (24 hour) basis and thus must be controlled by other endogenous circadian events. The specific aims will evaluate how these factors are controlled as well as why the nocturnal asthma patient does not readily awake so as to treat decreases in lung function as would occur more readily during the daytime hours. To these ends, the specific aims will determine: (1) if clock gene(s) expression in blood and lungs exhibit a circadian pattern and its relationship to certain other outcome factors as lung function, melatonin, and inflammatory markers; (2) if melatonin produces a state of enhanced inflammation that results in decreased steroid sensitivity; (3) if there is a dysregulation of corticotropin releasing hormone production in response to enhanced inflammation at night; and (4) the effects of melatonin on physiologic and arousal responses during sleep.

R01HL064804

2000-04-01

2004-03-31