title: Urine leukotriene E4 levels are associated with decreased pulmonary function in children with persistent airway obstruction.
abstract: BACKGROUND
  Use of leukotriene receptor antagonists improves disease control in children and adults with asthma. However, the relationship between cysteinyl leukotriene levels and indices of daily asthma control has not been studied directly.
  
  
  OBJECTIVE
  We sought to assess the relationship between daily variability in urinary leukotriene E(4) (LTE(4)) levels and daily lung function in children primarily taking inhaled corticosteroids (ICSs) and long-acting beta-agonists (LABAs).
  
  
  METHODS
  Fifty children primarily with moderate-to-severe asthma were followed with measurements of urinary LTE(4), monitoring of FEV(1), and albuterol use.
  
  
  RESULTS
  Increasing urinary LTE(4) levels were associated with significant (P = .006) decreases in percent predicted FEV(1) (ppFEV(1)) averaging 4.7% per interquartile range increase in LTE(4) and accompanied by increased albuterol use (P = .03). Children with lower FEV(1)/forced vital capacity ratios demonstrated larger LTE(4)-related FEV(1) decreases (6.4%) compared to those with higher ratios (4.2%, P = .009). This association was blunted in children taking montelukast (1.4% ppFEV(1) decrease) compared with that in children not taking this medication (5.4% ppFEV(1) decrease, P = .05). Children with lower lung function ratios demonstrated greater blunting of the LTE(4) effect with montelukast (0.9% ppFEV(1) decrease) compared to those with higher ratios (3.6% ppFEV(1), P = .0002).
  
  
  CONCLUSIONS
  Daily variability in LTE(4) levels is associated with clinically significant decreases in pulmonary function. In children who demonstrate a response associated with an increase in urinary LTE(4) levels, leukotriene receptor antagonists protect against daily FEV(1) decreases. This protection might be greatest in those with persistent airway obstruction despite use of ICS and LABA therapy.
  
  
  CONCLUSIONS
  Therapies designed to block cysteinyl leukotriene production or function might benefit children receiving ICS and LABA therapy who continue to experience persistent disease.
authors.affiliation: Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA. rabinovitchn@njc.org
authors.forename: Nathan
authors.initials: N
authors.lastname: Rabinovitch
authors.forename: Lening
authors.initials: L
authors.lastname: Zhang
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000085:Acetates / Q000008:administration & dosage; D000293:Adolescent; D000402:Airway Obstruction / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D000420:Albuterol / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine*; D002648:Child; D002908:Chronic Disease; D003521:Cyclopropanes; D004198:Disease Susceptibility; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D011804:Quinolines / Q000008:administration & dosage; D012720:Severity of Illness Index; D013440:Sulfides
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D017999:Leukotriene E4; C093875:montelukast; D000420:Albuterol