Circadian variation in airway function

  • Peter J. Barnes
    Requests for reprints should be addressed to Prof. Peter J. Barnes, Department of Clinical Pharmacology, Cardiothoracic Institute, London SW3, United Kingdom.
    Department of Medicine (Respiratory Division), Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom
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      Nocturnal asthma is a common and troublesome problem. Many possible mechanisms have been proposed, including exposure to allergens, sleep itself, the supine posture, withdrawal of bronchodilator drugs, gastric reflux, mucus plugging, and airway cooling. Although these may be contributory factors in individual patients, they cannot provide a universal explanation for the phenomenon of nocturnal and early morning wheezing. It now seems that nocturnal asthma may best be understood in terms of circadian rhythms. A circadian variation in airway caliber has been demonstrated in normal subjects; in asthmatic subjects, the same rhythm is present but with greater amplitude. The amplitude is magnified by bronchial hyper-responsiveness, a cardinal feature of asthma. Evidence now suggests that the fall in circulating epinephrine level at night removes an important defense against bronchoconstriction in asthmatic subjects, and this itself may be magnified by removal of the braking effect of epinephrine on mast cell mediator release. In addition, increased vagal reflex bronchoconstriction and the delayed effects of the fall in plasma cortisol level may also contribute to nocturnal wheezing. Thus, nocturnal asthma may be explained by a complex interaction of several coincident circadian rhythms, which produce only small changes in airway caliber in normal subjects; however, in asthmatic patients, these constrictor effects are magnified to produce bronchospasm severe enough to wake the patient.
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