title: Circadian variation of sputum inflammatory cells in mild asthma.
abstract: BACKGROUND
  Asthma, like many conditions, demonstrates a circadian rhythm with a worsening of lung function in the early morning hours compared with in the late afternoon.
  
  
  OBJECTIVE
  Because eosinophilic airway inflammation is a proposed mechanism for worsening asthma, we characterized circadian variation in airway eosinophils and determined its relationship to variability in airway function.
  
  
  METHODS
  Pulmonary function testing, sputum induction, and phlebotomy were performed at 7 am and 4 pm in 11 allergic subjects with mild asthma. Sputum was analyzed for cell viability, differential, and eosinophil-derived neurotoxin levels. IL-5 levels in serum were measured by means of ELISA.
  
  
  RESULTS
  Subjects had a significant decrease in FEV(1) (median [interquartile range] = 80% [70%-86%] vs 85% [82%-94%], P =.009) and a greater beta-agonist reversibility (median [interquartile range] = 13% [7%-32%] vs 8% [5%-14%], P =.024) in the early morning compared with in the late afternoon. Sputum analysis showed an increase in early morning total sputum leukocytes (median [interquartile range] = 4.3 x 10(6) [2.3 x 10(6) to 6.1 x 10(6)] vs 2.6 x 10(6) [1.7 x 10(6) to 3.6 x 10(6)], P =.044) and eosinophils (median [interquartile range] = 7.0 x 10(4) [2.7 x 10(4) to 18.7 x 10(4)] vs 3.6 x 10(4) [1.0 x 10(4) to 8.2 x 10(4)], P =.024). Furthermore, sputum eosinophils correlated with beta-agonist reversibility (R (s) = 0.665, P =.019). Finally, levels of IL-5 in serum and eosinophil-derived neurotoxin in sputum were significantly increased at 7 am.
  
  
  CONCLUSIONS
  These data suggest that circadian variability in pulmonary function in asthma could be related to changes in airway eosinophil recruitment and activation.
authors.affiliation: Pulmonary and Critical Care Section, Department of Medicine, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI 53792-9988, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Panzer
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dodge
authors.forename: Elizabeth A B
authors.initials: EA
authors.lastname: Kelly
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000276:immunology / Q000502:physiology; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D015848:Interleukin-5 / Q000097:blood; D012260:Ribonucleases / Q000378:metabolism; D013183:Sputum / Q000166:cytology* / Q000276:immunology
chemical_list: D015848:Interleukin-5; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases