Exposure to tobacco smoke increases leukotriene E4–related albuterol usage and response to montelukast

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Abstract

Background:

Cysteinyl leukotrienes (CysLTs) are important mediators of asthma in children. Predictors of susceptibility to CysLT effects have not been developed.

Objectives:

To identify susceptibility markers to CysLT effects and montelukast response.

Methods:

Twenty-seven schoolchildren were followed for 5 months with measurements of urinary leukotriene E4 (LTE4), cotinine, fractional exhaled nitric oxide (FENO), and monitoring of albuterol use. After a baseline run-in, children were randomized to receive daily montelukast or placebo without change in their current controller medications.

Results:

At baseline, a significant (P= .003) positive association was observed between LTE4 levels and albuterol use 2 days later. LTE4-related albuterol usage (ie, change per interquartile increase in LTE4) declined significantly after montelukast treatment (12% decline;P= .0005 for relative difference between intervals) but not placebo (2% increase;P= .80). Declines in LTE4-related albuterol usage between intervals tended to be greater in girls (P= .01 for girls;P= .21 for boys;P= .07 for interaction) and were greater among children with higher cotinine levels (P= .01 for high cotinine group;P= .17 for low cotinine group;P= .04 for interaction). Children with high LTE4 levels relative to FENO demonstrated significant (P= .05) declines in LTE4-related albuterol usage between intervals (P= .89 for low ratio group;P= .25 for interaction).

Conclusion:

Increased individual CysLT levels are associated with subsequent albuterol usage. CysLT–related albuterol usage and montelukast responsiveness are increased in children exposed to tobacco smoke and tend to be greater in girls than boys. Measurement of LTE4 to FENO ratios may help predict susceptibility to montelukast.

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