Urinary leukotriene E4 and 9α, 11β-prostaglandin F2 concentrations in mild, moderate and severe asthma, and in healthy subjects


Prof. Philip Thompson, Asthma & Allergy Research Institute Inc., Ground Floor, E Block, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia.
E-mail: pjthomps@aari.uwa.edu.au


Background Airway inflammation in asthma is associated with cysteinyl leukotriene and prostaglandin D2 production. Measurement of urinary metabolites of these eicosanoids may be useful for monitoring asthma patients. However, the influence of asthma phenotype and severity on basal urinary excretion of these metabolites is unknown.

Objective To compare urinary leukotriene (LT)E4 and 9α, 11β-prostaglandin (PG)F2 concentrations in large groups of mild, moderate and severe asthmatic patients and healthy control subjects.

Methods Asthma severity, treatment and aspirin sensitivity were assessed by questionnaire in 168 asthmatic patients. Basal LTE4 and 9α, 11β-PGF2 concentrations were measured in urine samples from these patients and from 175 control subjects using enzyme immunoassays.

Results Urinary LTE4 was correlated with 9α, 11β-PGF2 in both control subjects and asthmatic patients (P<0.002). Median LTE4 and 9α, 11β-PGF2 concentrations in patients with severe asthma were significantly reduced compared with mild asthmatic patients (P<0.05 and <0.001, respectively). Urinary 9α, 11β-PGF2, but not LTE4 was lower in asthmatic patients using inhaled corticosteroids (P<0.02). Multiple regression analysis indicated that urinary 9α, 11β-PGF2 concentration was negatively correlated with asthma severity (P=0.003) and also with % predicted FEV1 (forced expiratory volume in 1 s) (P=0.005).

Conclusions Baseline urinary LTE4 and 9α, 11β-PGF2 concentrations are of limited value in discriminating between patients with different severities of asthma. Reduced urinary LTE4 and 9α, 11β-PGF2 in patients with severe asthma suggest that direct or indirect effects of high-dose corticosteroid therapy combined with other factors associated with severe asthma may influence eicosanoid production. However, the negative association of urinary 9α, 11β-PGF2 with lung function suggests an adverse effect of chronic PGD2 production on lung function in asthma, irrespective of severity.