Identification of diurnal rhythmic blood markers in bronchial asthma.

Rationale: Asthma is a rhythmic inflammatory disease of the airway, regulated by the circadian clock. ‘Spill-over’ of airway inflammation into the systemic circulation occurs in asthma and is reflected in circulating immune cell repertoire.
Objectives: To determine how asthma impacts peripheral blood diurnal rhythmicity.
Methods: 10 healthy and 10 mild/moderate asthma participants were recruited to an overnight study. Blood was drawn every 6 hours for 24 hours.
Main Results: The molecular clock in blood cells in asthma is altered; Per3 is significantly more rhythmic in asthma compared to healthy. Blood immune cell numbers oscillate throughout the day, in health and asthma. Peripheral blood mononucleocytes from asthma patients show significantly enhanced responses to immune stimulation and steroid suppression at 16:00, compared to at 04:00. Serum ceramides, show complex changes in asthma; some losing, and others gaining rhythmicity.
Conclusions: This is the first report showing asthma is associated with a gain in peripheral blood molecular clock rhythmicity. Whether the blood clock is responding to rhythmic signals received from the lung or driving rhythmic pathology within the lung itself is not clear. Dynamic changes occur in serum ceramides in asthma, likely reflecting systemic inflammatory action. The enhanced responses of asthma blood immune cells to glucocorticoid at 16:00 may explain why steroid administration is more effective at this time.