Clinical chronobiology and chronotherapeutics with applications to asthma

The concept of homeostasis (i.e., constancy of the milieu interne) has long dominated the teaching and practice of medicine. Concepts and findings fro m chronobiology, the scientific study of biological rhythms, challenge this construct. Biological processes and functions are not at all constant; rat her, they are organized in time as rhythms with period lengths that range i n duration from as short as a second or less to as long as a year. It is th e body's circadian (24h) rhythms that have been researched most intensely. The peak and trough of these rhythms are ordered rather precisely in time t o support the biological requirements of activity during the day and sleep at night. The timing of the peak and trough plus the magnitude of variation (amplitude) of physiological and biochemical functions during the 24h give rise to predictable-in-time, day-night patterns in the manifestation and e xacerbation of many common medical conditions. Circadian rhythms also can i nfluence the response of patients to diagnostic tests and therapeutic inter ventions according to their timing with reference to body rhythms. Rhythms in the pathophysiology of medical conditions and patient tolerance to medic ations constitute the basis for chronotherapeutics, the timing of treatment in relation to biological rhythm determinants as a means of optimizing ben eficial effects and safety. The article discusses recent advances in medica l chronobiology and chronotherapeutics and their relevance to clinical medi cine in general and the management of asthma in particular. Indeed, since a sthma is a disease that exhibits rather profound circadian rhythmicity, inv estigation of its pathophysiology and therapy necessitates a chronobiologic approach.