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 FEV1 (median [interquartile range] = 80% [70%-86%] vs 85% [82%-94%], P = .009) and a greater β-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 × 106 [2.3 × 106 to 6.1 × 106] vs 2.6 × 106 [1.7 × 106 to 3.6 × 106], P = .044) and eosinophils (median [interquartile range] = 7.0 × 104 [2.7 × 104 to 18.7 × 104] vs 3.6 × 104 [1.0 × 104 to 8.2 × 104], P = .024). Furthermore, sputum eosinophils correlated with β-agonist reversibility (Rs = 0.665, P = .019). Finally, levels of IL-5 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.