E A B Kelly1, J J Houtman, N N Jarjour. 1. Pulmonary and Critical Care Medicine Section, Department of Medicine, University of Wisconsin, Madison, WI 53792, USA. eak@medicine.wisc.edu
Abstract
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.
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.
Authors: Sarah Kirsch; Stephan Thijssen; Susana Alarcon Salvador; Gunnar H Heine; Kai van Bentum; Danilo Fliser; Martina Sester; Urban Sester Journal: J Clin Immunol Date: 2012-07-15 Impact factor: 8.317