Mechanisms and Therapeutic Implications of Asthma Circadian Rhythm

Nocturnal worsening of asthma is very common and employed in clinical practice as a marker of asthma severity. The fall in overnight lung function can reach 50%. Several mechanisms contribute to this circadian (24 h) variation. Cortisol, steroid responsiveness, vagal tone, leukotriene, airway inflammation and airway hyperresponsiveness vary in a circadian fashion and have been described as potential mechanisms. Studies on the ability of corticosteroids to block circadian recruitment of inflammatory cells show that a single corticosteroid systemic dose in the afternoon results in a significant pancellular reduction in bronchoalveolar lavage cytology at 4: 00 h and a reduction in the overnight fall in FEV1. The same single dose in the morning or night does not lead to significant improvement. Further studies on chronotherapy of asthma have revealed a rapid and time-dependent effect of inhaled steroids. A single dose of inhaled steroid in the afternoon has a protective effect against asthma worsening in the same night. Chronotherapeutic principles are also applied with other than corticosteroid drugs in the regular asthma treatment.