Airway purinergic responses in healthy, atopic nonasthmatic, and atopic asthmatic subjects exposed to ozone

Objective: To examine the relationships between airway purine metabolites and established inflammatory markers of ozone exposure, and to determine if these relationships are altered in individuals with atopy or asthma. Materials and methods: Mass spectrometry was utilized to measure concentrations of purine metabolites (adenosine monophosphate [AMP], adenosine, hypoxanthine, uric acid) and non-purine metabolites (taurine, urea, phenylalanine, tyrosine) in induced sputum obtained from 31 subjects with normal lung function (13 healthy controls, eight atopic nonasthmatics, and 10 atopic asthmatic [AA]) before and 4 h after ozone exposure. Results: At baseline, the purines AMP and hypoxanthine correlated with multiple inflammatory markers including neutrophil counts and the cytokines interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-alpha alpha), and IL-1 beta beta (r ranged from 0.41 to 0.66, all P < 0.05). Following ozone exposure, these purines remained correlated with IL-6, IL-8, and TNF-alpha alpha (r == 0.37--0.68). However, AMP and hypoxanthine increased significantly post ozone exposure in atopic nonasthmatics but not in AA. In contrast, the non-purine metabolite taurine correlated with baseline neutrophil counts (r == 0.56) and IL-6 (r == 0.53) and was elevated post-exposure in both atopic cohorts. Discussion and conclusions: The purine metabolites AMP and hypoxanthine are correlated with multiple inflammatory markers at baseline and after ozone exposure. However, changes in these purine metabolites after ozone appear to differ from other inflammatory markers, with less response in AA relative to atopic nonasthmatics. Purine metabolites may play a role in the signaling responses to ozone, but these responses may be altered in subjects with asthma.