Breathing around the clock: an overview of the circadian pattern of respiration

This article reviews human and animal studies about the circadian patterns of physiological variables involved with the respiratory function. Some measures reflecting the mechanical properties of the lungs, such as functional residual capacity, forced expiratory volumes and airway resistance, change periodically with the time of the day. Also resting pulmonary ventilation (V(E)), tidal volume, and breathing rate follow circadian patterns. In humans, these patterns occur independently of the daily changes in activity, whereas, to some extent, they are linked to changes in the state of arousal. Differently, in some rodents, the circadian oscillations of the breathing pattern occur independently of the daily rhythms of either activity or state of arousal. Recent measurements of the breathing pattern for unlimited periods of time in undisturbed animals have indicated that the circadian changes occur in close temporal phase with those of oxygen consumption, carbon dioxide production, and body temperature. However, none of these variables can fully explain the circadian pattern of breathing, the origin of which remains unclear. Both in humans and in rats the V(E) responses to hypercapnia or hypoxia differ at various times of the day. In rats, the daily differences in V(E) responses are buffered by changes in metabolic rate, such that, unlike humans, the hyperventilation (defined as the increase in ventilation-metabolism ratio) remains constant throughout the 24 h. The presence of a biological clock is a major advantage in the adaptation to the environment, although it forces some variables to deviate periodically from their mean value. In humans, these deviations become apparent in conditions of hypoxia. Hence, a daily time-window exists in which the respiratory system is less capable of responding to challenges, a factor which may contribute to the findings that some cardio-respiratory symptoms and diseases peak at particular times of the day.