The Circadian Biology of Asthma

Background: Asthma is a chronic inflammatory disease of the airways. It is common (1:12 adults in UK) and the prevalence is increasing. There is marked time of day variation in both symptoms and lung physiological parameters. Emergence of night-time symptoms in asthma often leads to an escalation in treatment. Furthermore, drug companies trialling new inhaled corticosteroids (ICS) use a reduction in the morning ‘dip’ in lung physiology as a primary outcome measure. The pathogenesis of the circadian variation in asthma is unknown. Furthermore, increasing evidence suggests that ICS may be more effective in the afternoon (3pm), rather than traditional morning or evening dosing. Understanding of the circadian biology of asthma is crucial for improved therapeutics.
Aim: To investigate the circadian biology of asthma.
• Define new biochemical pathways involved in the circadian variation in asthma
• Determine a circadian biomarker in asthma
Method: We recruited 10 atopic, moderately severe asthmatics and 10 healthy volunteers to complete 4 study visits, including an overnight stay. Blood, induced sputum and breath were sampled at intervals throughout the day and night, and physiological measurements made.
REC reference: 14/NW/1352.
Results: There is a high amplitude circadian change in FEV1 in asthmatics compared to healthy controls. The nadir is at 4am (figure 1). There was also an increase in sputum eosinophils (a key effector cell in asthma) at 4am compared to 4pm in asthmatics.
Figure 1
Discussion: We have demonstrated a significant diurnal effect on asthma lung physiology. Further downstream analysis of serum, breath and sputum is underway.