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

Clin Exp Allergy. 2004 Feb;34(2):227-33. doi: 10.1111/j.1365-2222.2004.01866.x.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Asthma / immunology*
  • Asthma / physiopathology*
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Circadian Rhythm*
  • Eosinophil-Derived Neurotoxin
  • Female
  • Forced Expiratory Volume
  • Humans
  • Interleukin-5 / analysis
  • Lung / immunology*
  • Lung / physiopathology*
  • Lymphocyte Count
  • Macrophages, Alveolar / immunology
  • Male
  • Neutrophils / immunology
  • Phytohemagglutinins / pharmacology
  • Ribonucleases / analysis
  • Statistics, Nonparametric


  • Interleukin-5
  • Phytohemagglutinins
  • Eosinophil-Derived Neurotoxin
  • Ribonucleases