Nocturnal asthma: circadian rhythms and therapeutic interventions

The pathophysiology of nocturnal asthma is closely associated with chronobiology, the science of biologic processes that have time-related rhythms. The 24-h cycle (circadian rhythm) is especially important in understanding the changes in pulmonary function that occur in sleeping asthmatics. Nocturnal asthma can be seen as representing an exaggerated amplitude of normal circadian patterns, including increased airway responsiveness and decreased lung function at night and in the early morning. Circadian changes in epinephrine, AMP, histamine and other inflammatory mediators, cortisol, vagal tone, body temperature, and lower airway secretions are potential mechanisms that favor nocturnal bronchoconstriction. Circadian variation in pulmonary function, as well as the effect of therapeutic interventions, can be readily demonstrated by having patients record peak expiratory flow rate values at different times of the day and night, using a peak flow meter. The treatment of nocturnal asthma requires a chronopharmacologic approach, in which more intense therapy is targeted to coincide with the time that the disease is the worst. Chronopharmacology includes the strategic use of longer-acting beta-agonists, theophylline, corticosteroids, and anticholinergics. Understanding the kinetics of the different drug preparations is necessary for most effective timing of dose. Future treatment of nocturnal asthma will continue to be guided by increased understanding of circadian and sleep-related events.