Nocturnal asthma: mechanisms and the role of theophylline in treatment.

Abstract

Asthma is characterized by airway inflammation and hyper-responsiveness. Clinically, these features are manifested by attacks of cough, wheezing, and dyspnoea. Nocturnal asthma symptoms are frequent; 39% of asthmatics awaken nightly, and 94% have nocturnal awakenings at least once a month. A number of mechanisms have been hypothesized to explain the phenomenon of nocturnal asthma, including exposure to dust mite allergen, late-phase allergic reactions, effects of posture and sleep stage on airway tone, gastro-oesophageal reflex, impaired mucociliary clearance, airway cooling, and changes in circadian rhythms of circulating hormones. While no single mechanism can explain these changes, circadian rhythms may be particularly relevant. Normal airway tone increases during sleep and is magnified in asthmatics. Bronchial responsiveness to histamine and allergen challenge increases during sleep and mast cell mediator release is enhanced. Circulating eosinophils increase, which may allow their ingress into pulmonary tissue. Decreases in plasma catecholamine and cortisol levels have also been observed. All of these may influence airway tone, inflammation, and responsiveness during sleep and produce the observed clinical picture. Inhaled sympathomimetics are frequently ineffective in preventing nocturnal symptoms due to their short duration of action. While corticosteroids, cromoglycate, and anticholinergics are effective, sustained-release theophylline is particularly advantageous for controlling nocturnal symptoms. Once-daily theophylline when dosed in the evening not only controls nocturnal symptoms and improves airflow during the early morning hours, but decreases airway responsiveness to histamine as well. The close association between airway inflammation, airway hyper-responsiveness, and nocturnal asthma symptoms makes further studies of the mechanism of action of theophylline especially interesting.