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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL064815-01
Application #
6090980
Study Section
Special Emphasis Panel (ZHL1-CSR-H (F1))
Project Start
2000-04-01
Project End
2004-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
1
Fiscal Year
2000
Total Cost
$516,108
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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Scheer, Frank A J L; Hilton, Michael F; Mantzoros, Christos S et al. (2009) Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A 106:4453-8
Scheer, F A J L; Zeitzer, J M; Ayas, N T et al. (2006) Reduced sleep efficiency in cervical spinal cord injury; association with abolished night time melatonin secretion. Spinal Cord 44:78-81
Shea, Steven A; Hilton, Michael F; Orlova, Christine et al. (2005) Independent circadian and sleep/wake regulation of adipokines and glucose in humans. J Clin Endocrinol Metab 90:2537-44
Hu, Kun; Ivanov, Plamen Ch; Chen, Zhi et al. (2004) Non-random fluctuations and multi-scale dynamics regulation of human activity. Physica A 337:307-18
Hu, Kun; Ivanov, Plamen Ch; Hilton, Michael F et al. (2004) Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior. Proc Natl Acad Sci U S A 101:18223-7