The Respiratory System

Abstract

Rhythms in lung function and time-of-day-dependent exacerbation in disease symptoms have been noted dating back to the 5th century. Today, we recognize the 24-hour variation in normal lung function and how these fluctuations are associated with the circadian component of lung pathophysiology. Diseases of the airway such as allergic asthma, COPD, pulmonary fibrosis, pneumonia and sepsis, and lung cancer all have documented correlations with circadian rhythm and the peripheral molecular clock. Additionally, chronic exposure to particulate matter and other pollutants can induce alterations in clock genes/proteins, and disruption of the circadian system increases susceptibility to poor outcomes following insult to the airway. Investigations into targets of the molecular clock have shed light on chronotherapeutics that can be used to optimize therapeutic approaches in the clinic or leverage endogenous circadian networks to enhance efficacy of currently available treatments.