Increase in urinary leukotriene LTE4 levels in acute asthma: correlation with airflow limitation.
BACKGROUND
Leukotrienes play a key role in the pathophysiology of chronic asthma. Activation of leukotriene pathways is accompanied by rises in detectable urinary levels of leukotriene E4 (LTE4). The relationship between urinary LTE4 levels and factors associated with acute asthma has not been determined.


METHODS
Adults aged 15-54 years presenting with moderate to severe acute asthma were evaluated at emergency departments in 16 US sites. Forced expiratory volume in 1 second (FEV1) was measured during the first 60 minutes after arrival and at specified times until discharge or admission. Urine samples for measurement of LTE4 levels were obtained either on arrival at the study site and/or before discharge. Patients were seen 2 weeks later for follow up, at which time repeat FEV1 measurements and urine samples for LTE4 were obtained.


RESULTS
One hundred and eighty four patients were evaluated; LTE4 results from both the acute and follow up periods were available for analysis in 146. Urinary LTE4 levels were increased during asthma exacerbations compared with levels obtained 2 weeks later (geometric means 111.7 and 75.6 pg/mg creatinine, respectively, mean percentage change -32.3; 95% confidence interval (CI) for the mean percentage change -39.6 to -24.3, p<0.001). The correlation between improvement in FEV1 and decline in LTE4 over the 2 week interval was significant (p<0.001, r=0.43).


CONCLUSIONS
Activation of leukotriene pathways in acute asthma is correlated with the degree of airflow obstruction, and resolution of the asthma exacerbation is associated with a reduction in leukotriene levels.
Green
S A
SA
Merck Research Laboratories, Rahway, NJ, USA. stuart_green@merck.com
Malice
M-P
MP
Tanaka
W
W
Tozzi
C A
CA
Reiss
T F
TF
D000085:Acetates / Q000008:administration & dosage; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D003521:Cyclopropanes; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D020024:Leukotriene Antagonists / Q000008:administration & dosage; D017999:Leukotriene E4 / Q000652:urine*; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage; D013440:Sulfides
D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D017999:Leukotriene E4; C093875:montelukast