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Inflammatory changes associated with circadian variation in pulmonary function in subjects with mild asthma


Dr Becky Kelly, Section of Pulmonary and Critical Care Medicine, 600 Highland Avenue, CSC K4/928, University of Wisconsin School of Medicine, Madison, WI 53792-9988, USA.


Background Nocturnal enhancement of airway inflammation has been demonstrated in patients with asthma who have a significant drop in pulmonary function at night.

Objective To investigate the circadian changes in airway inflammation and their relationship with variations in pulmonary function in subjects with mild atopic asthma.

Methods Twelve asthma subjects were admitted to the hospital for two separate 24-h visits. Bronchoalveolar lavage (BAL) was performed at 04:00 hours during one visit, and at 16:00 hours during another visit. BAL cells were analysed for lymphocyte phenotype and the capacity to secrete cytokines following ex vivo stimulation with phytohaemagglutinin (PHA).

Results The numbers of BAL lymphocytes and the percentage of CD4+ T cells were higher at 04:00 hours compared with 16:00 hours. At 04:00 hours, the forced expiratory volume in 1 s (FEV1) was inversely correlated with BAL lymphocytes and CD4+ cells. PHA-induced generation of IL-5 by BAL cells correlated with BAL eosinophils and CD4+ cells. Moreover, there was a linear relationship between the relative change (16:00–04:00 hours) in IL-5 and circadian variation in FEV1.

Conclusions These data suggest that the circadian variation in lung function in asthma is associated with increased airway CD4+ lymphocyte numbers and their capacity to generate IL-5. Furthermore, in mild asthma, these circadian changes appear to fall into a continuous range, suggesting that day/night variations in airway inflammation and lung function occur on a continuum, rather than as an all-or-none phenomenon.