Exposure to tobacco smoke increases leukotriene E4-related albuterol usage and response to montelukast.
BACKGROUND
Cysteinyl leukotrienes (CysLTs) are important mediators of asthma in children. Predictors of susceptibility to CysLT effects have not been developed.


OBJECTIVE
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 (LTE(4)), 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 LTE(4) levels and albuterol use 2 days later. LTE(4)-related albuterol usage (ie, change per interquartile increase in LTE(4)) declined significantly after montelukast treatment (12% decline; P = .0005 for relative difference between intervals) but not placebo (2% increase; P = .80). Declines in LTE(4)-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 LTE(4) levels relative to FENO demonstrated significant (P = .05) declines in LTE(4)-related albuterol usage between intervals (P = .89 for low ratio group; P = .25 for interaction).


CONCLUSIONS
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 LTE(4) to FENO ratios may help predict susceptibility to montelukast.
Rabinovitch
Nathan
N
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colo 80206, USA. rabinovitchn@njc.org
Strand
Matthew
M
Stuhlman
Kate
K
Gelfand
Erwin W
EW
D000085:Acetates / Q000627:therapeutic use*; D000293:Adolescent; D000420:Albuterol / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D015415:Biomarkers / Q000652:urine; D001944:Breath Tests; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002648:Child; D003367:Cotinine / Q000652:urine; D003521:Cyclopropanes; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D011804:Quinolines / Q000627:therapeutic use*; D012737:Sex Factors; D013440:Sulfides; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D000085:Acetates; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D014028:Tobacco Smoke Pollution; D009569:Nitric Oxide; D017999:Leukotriene E4; D003367:Cotinine; C093875:montelukast; D000420:Albuterol