Prostaglandin E2 and cysteinyl leukotriene concentrations in sputum: association with asthma severity and eosinophilic inflammation

BACKGROUND: Inflammation of the airways in asthma is associated with the production of cysteinyl leukotrienes (cysLT), prostaglandin (PG)E(2), 8-isoprostane, nitric oxide and other mediators. However, the relationship between asthma severity or eosinophilic inflammation and the concentrations of mediators in sputum is unclear. OBJECTIVE: To assess sputum PGE(2), cysLT, 8-isoprostane and nitrate concentrations, as well as urinary leukotriene (LT)E(4) and 9alpha,11beta-prostaglandin (PG)F(2) concentrations, in patients with differing severities of asthma and eosinophilic or non-eosinophilic airway inflammation. METHODS: Inflammatory cells in sputum were assessed in 12 patients with mild, 14 with moderate and 12 with severe persistent asthma, as well as in 13 control subjects. Asthmatic patients were categorized into those with eosinophilic or non-eosinophilic airway inflammation. Sputum PGE(2), cysLT and 8-isoprostane, and urinary LTE(4) were extracted on immunoaffinity sorbents, and the concentrations of all mediators were measured using enzyme immunoassays. Sputum nitrate concentrations were measured on a chemiluminescence analyzer. RESULTS: Sputum PGE(2) concentrations were higher in both moderate (1710 pg/mL) and severe asthmatic (1590 pg/mL) compared with control subjects (827 pg/mL) (P<0.05). CysLT concentrations were higher in moderate asthmatic compared with control or severe asthmatic subjects (P<0.05). Sputum PGE(2) concentrations were lower in patients with eosinophilic (1180 pg/mL) compared with non-eosinophilic airway inflammation (2520 pg/mL) (P=0.02). In contrast, sputum cysLT and urinary LTE(4) concentrations were higher in those with eosinophilic airway inflammation (P<0.05). Forced expiratory volume in 1 s was inversely correlated with sputum eosinophils in all asthmatic patients (r(s)=-0.5, P=0.002). There were no significant differences in sputum 8-isoprostane or nitrate concentrations. CONCLUSIONS: Increased airway concentrations of PGE(2) are consistent with the hypothesis that PGE(2) has a bronchoprotective and anti-inflammatory role in patients with more severe asthma. A reduced PGE(2) to cysLT ratio in the airways may adversely affect lung function and contribute to persistence of symptoms and airway remodelling in patients with eosinophilic airway inflammation.