Circadian Variation of Exhaled Nitric Oxide and Urinary Eosinophil Protein X in Asthmatic and Healthy Children

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Abstract
Asthmatic symptoms and the frequency of admissions to hospital because of acute asthma tend to increase in the early morning hours, and it is therefore possible that airway inflammation increases during the night. To elucidate the hypothetical circadian variation of airway inflammation, we measured concentrations of exhaled nitric oxide (FeNo), urinary eosinophil protein X excretion (EPX), and forced expiratory volume in the first second (FEV1) in 20 asthmatic and 6 nonatopic nonasthmatic children every 3 h during a 21-h period. Compared with control subjects, asthmatic subjects had higher FeNo (median, 22.7 versus 10.3 ppb, p = 0.016) and lower FEV1 % predicted (median, 91.0 versus 101.9%, p = 0.045), but did not differ significantly in EPX (median, 153.8 versus 148.7 μg/mmol creatinine, p = 0.83) at 7 AM. However, differences in gender and age do not allow direct comparisons between asthmatic and control children. FeNo and EPX demonstrated a cosinelike circadian rhythm (log FeNo, p = 0.0001; log EPX, p = 0.0001) with lowest levels at 7 PM and highest at 7 AM. This was also the case for FEV1 % (p = 0.01). No difference in the amplitude of circadian rhythm was observed between asthmatic and healthy control children for log FeNo (p = 0.35), log EPX (p = 0.57), and FEV1 % (p = 0.17). A stratified analysis showed a significant circadian rhythm in the control group for log FeNo (p = 0.014) and log EPX (p = 0.0001). Our results therefore suggest a circadian rhythm of inflammatory markers, which peaks in the early morning. Rhythmicity of EPX excretion and FeNo in healthy children suggests a physiologic mechanism; however, pathologic effects during the night might occur under conditions of asthma-specific inflammation.