Circadian Changes in the Sputum of Asthmatic Subjects and Healthy Controls

BACKGROUND: Asthma is exhibiting classical circadian fluctuations of clinical symptoms and airflow measurements, presumably influenced by the underlying airway inflammation and the endogenous cortisol secretion. The aim of our study was to examine the cellular and eosinophilic cationic protein (ECP) contents of sputum, collected and frozen at 2 opposite time points of the day-and-night cycle, and to correlate them to blood cortisol levels. METHODS: Thirteen subjects with uncontrolled asthma (8 men, aged 25-54 years) and 10 healthy subjects (6 men, aged 25-50 years) volunteered for the study. They were induced with hypertonic saline to produce sputum between 8:00 AM and 9:00 AM and between 8:00 PM and 9:00 PM, when blood was also withdrawn to measure cortisol levels. RESULTS: Asthmatic subjects did not display significant morning/evening differences in their sputum total cell counts ([TCCs] median, 2.06 × 10(3 )cells/mL; range 0.50-5.66 cells/mL vs median, 1.29 cells/mL; range, 0.24-9.26 cells/mL, P > 0.1), whereas controls had a well-defined morning peak (median, 0.75 cells/mL; range, 0.31-2.25 cells/mL vs median, 0.33 cells/mL; range, 0.1-0.97 cells/mL, P > 0.001). Asthmatic subjects had significantly higher sputum TCC than controls in the evening (P < 0.001), but their morning TCC did not significantly exceed those of the healthy subjects. Asthmatic subjects had significantly more sputum eosinophils and higher ECP levels than controls but failed to demonstrate significant morning/evening differences in contrast to the controls who had higher morning eosinophils and ECP. Macrophages were relatively increased in the evening samples of both asthmatic subjects and controls. No significant correlations between the circadian cortisol shift and any of the sputum indices were found. CONCLUSIONS: Sputum undergoes circadian changes, which are different in health and in asthma and do not correlate with endogenous cortisol levels.