Urinary leukotriene E4 and 9 alpha, 11 beta-prostaglandin F concentrations in mild, moderate and severe asthma, and in healthy subjects.
BACKGROUND
Airway inflammation in asthma is associated with cysteinyl leukotriene and prostaglandin D(2) 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)E(4) and 9 alpha, 11 beta-prostaglandin (PG)F(2) 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 LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations were measured in urine samples from these patients and from 175 control subjects using enzyme immunoassays.


RESULTS
Urinary LTE(4) was correlated with 9 alpha, 11 beta-PGF(2) in both control subjects and asthmatic patients (P<0.002). Median LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations in patients with severe asthma were significantly reduced compared with mild asthmatic patients (P<0.05 and <0.001, respectively). Urinary 9 alpha, 11 beta-PGF(2), but not LTE(4) was lower in asthmatic patients using inhaled corticosteroids (P<0.02). Multiple regression analysis indicated that urinary 9 alpha, 11 beta-PGF(2) concentration was negatively correlated with asthma severity (P=0.003) and also with % predicted FEV(1) (forced expiratory volume in 1 s) (P=0.005).


CONCLUSIONS
Baseline urinary LTE(4) and 9 alpha, 11 beta-PGF(2) concentrations are of limited value in discriminating between patients with different severities of asthma. Reduced urinary LTE(4) and 9 alpha, 11 beta-PGF(2) 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 9 alpha, 11 beta-PGF(2) with lung function suggests an adverse effect of chronic PGD(2) production on lung function in asthma, irrespective of severity.
Misso
N L A
NL
Cooperative Research Centre for Asthma, The University of Western Australia, Perth, Australia.
Aggarwal
S
S
Phelps
S
S
Beard
R
R
Thompson
P J
PJ
D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D015237:Dinoprost / Q000652:urine*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012720:Severity of Illness Index
D015415:Biomarkers; D005938:Glucocorticoids; D017999:Leukotriene E4; D015237:Dinoprost