Circadian variation of sputum inflammatory cells in mild asthma.
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.
Panzer
Sarah E
SE
Pulmonary and Critical Care Section, Department of Medicine, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI 53792-9988, USA.
Dodge
Ann M
AM
Kelly
Elizabeth A B
EA
Jarjour
Nizar N
NN
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
D015848:Interleukin-5; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases