Chronobiology and chronopathophysiology of nocturnal asthma.

Asthma is increasing in prevalence and severity worldwide despite effective treatment and innovative research developments. Chronobiology is the study of biological rhythms and their mechanisms. Asthma is one of many diseases that exemplifies a circadian pattern in intensity, frequency of attacks and mortality. As many as 90% of asthmatics experience nocturnal symptoms severe enough to awaken them from sleep. Increased airway narrowing at night is thought to occur as a result of circadian variation in neurohormones and intensification of airway inflammation. Furthermore, vagal tone, neurogenic inflammation and airway hyperresponsiveness are increased at night. Many cells contribute to the nocturnal inflammatory process in the asthmatic airways, including mast cells, eosinophils, neutrophils and lymphocytes. These cells are capable of secreting innumerable inflammatory mediators, such as histamine, cytokines, leukotrienes, prostaglandins, neutral endopeptidase and superoxides, which are potent bronchoconstrictors and secretogogues. They also cause increased vascular permeability and airway oedema. All these chronobiological events promote nocturnal worsening of asthma and increased nocturnal deaths. Understanding the mechanisms of nocturnal asthma will help us learn more about asthma, and how to implement appropriate chronotherapeutic interventions.