There exists a disproportionately high frequency of asthmatic events during the latter half of the usual sleep episode. Patients with nocturnal asthma demonstrate increased morbidity and mortality relative to other patients with asthma. Diurnal studies involving repeated measurements during the sleep/wake cycle, sleep deprivation or shift work suggest the existence of separate sleep and circadian dependent effects on bronchoconstriction. Recent data from established circadian protocols clearly indicate significant circadian rhythms in pulmonary function and respiratory control in healthy subjects, and that indices of airways inflammation have a diurnal rhythm (circadian and sleep/wake cycles not separated) in patients with asthma and healthy controls. The primary aim is to test the hypothesis that asthma severity is affected by separate circadian influences (independent of sleep) and sleep/wake cycle influences (independent of circadian rhythm). The principal dependent variables include bronchoconstriction (spirometry and airways resistance) and asthma symptoms (validated questionnaire and usage of any rescue medication). To overcome methodological problems with previous studies a 'forced desynchrony' protocol will be used, wherein subjects sleep and wake episodes occur at all phases of the circadian cycle. This will be accomplished by scheduling a recurring artificial day length of 28 hours throughout a 10-day protocol in healthy subjects and patients with nocturnal asthma.
The specific aims will test the hypotheses that 1) bronchoconstriction is influenced by separate circadian and sleep/wake effects; 2) bronchoconstriction is affected by circadian or sleep/wake influences on airway inflammation; and 3) bronchoconstriction is affected by circadian or sleep/wake influences on sympatho-vagal balance.
