Circadian variation of sputum inflammatory cells in mild asthma

Background: Asthma, like many conditions, demonstrates a cireadian 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 rela. tionship 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 FEV1 (median [interquartile range] = 80% [70%-86%] vs 85% [82%-94%], P =.009) and a greater P-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 104 [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 IL5 in serum and eosinophil-derived neurotoxin in sputum were significantly increased at 7 Am. conclusion: These data suggest that circadian variability in pulmonary function in asthma could be related to changes in airway eosinophil recruitment and activation. (J Allergy Clin Immunol 2003;111:308-12.).