title: The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma.
abstract: OBJECTIVE
  To evaluate the effectiveness of inhibiting the formation of the 5-lipoxygenase products of arachidonic acid by the 5-lipoxygenase inhibitor zileuton in the treatment of mild-to-moderate asthma.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled study.
  
  
  METHODS
  University hospitals and private allergy and pulmonary practices.
  
  
  METHODS
  A total of 139 persons with asthma who had a forced expiratory volume in 1 second (FEV1) of 40% to 75% of the predicted value and who were not being treated with inhaled or oral steroids.
  
  
  METHODS
  Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks.
  
  
  METHODS
  Airway function, beta-agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4).
  
  
  RESULTS
  Zileuton produced a 0.35-L (95% CI, 0.25 to 0.45 L) increase in the FEV1 within 1 hour of administration (P < 0.001 compared with placebo), equivalent to a 14.6% increase from baseline. After 4 weeks of zileuton therapy, airway function and symptoms improved, with the greatest improvements occurring in the 2.4 g/d group: This group's FEV1 increased by 0.32 L (CI, 0.16 to 0.48 L), a 13.4% increase, compared with a 0.05-L (CI, -0.10 to 0.20 L) increase in patients taking placebo (P = 0.02). Symptoms and frequency of beta-agonist use also decreased with zileuton, 2.4 g/d. The mean urinary LTE4 level decreased by 39.2 pg/mg creatinine (CI, 18.1 to 60.4 pg/mg creatinine) and 26.5 pg/mg creatinine (CI, 6.6 to 46.5 pg/mg creatinine) in the 2.4 g/d and 1.6 g/d groups, respectively, compared with a slight increase in the placebo group (P = 0.007 and P = 0.05). No difference was noted in the number of adverse events among treatment groups.
  
  
  CONCLUSIONS
  Inhibition of 5-lipoxygenase can improve airway function and decrease symptoms and medication use in patients with asthma, suggesting that this inhibition can be useful therapy for asthma. Also, 5-lipoxygenase products may mediate part of the baseline airway obstruction in patients with mild-to-moderate asthma.
authors.affiliation: Pulmonary and Critical Care Division, Beth Israel Hospital, Boston, MA 02215.
authors.forename: E
authors.initials: E
authors.lastname: Israel
authors.forename: P
authors.initials: P
authors.lastname: Rubin
authors.forename: J P
authors.initials: JP
authors.lastname: Kemp
authors.forename: J
authors.initials: J
authors.lastname: Grossman
authors.forename: W
authors.initials: W
authors.lastname: Pierson
authors.forename: S C
authors.initials: SC
authors.lastname: Siegel
authors.forename: D
authors.initials: D
authors.lastname: Tinkelman
authors.forename: J J
authors.initials: JJ
authors.lastname: Murray
authors.forename: W
authors.initials: W
authors.lastname: Busse
authors.forename: A T
authors.initials: AT
authors.lastname: Segal
authors.forename: J
authors.initials: J
authors.lastname: Fish
authors.forename: H B
authors.initials: HB
authors.lastname: Kaiser
authors.forename: D
authors.initials: D
authors.lastname: Ledford
authors.forename: S
authors.initials: S
authors.lastname: Wenzel
authors.forename: R
authors.initials: R
authors.lastname: Rosenthal
authors.forename: J
authors.initials: J
authors.lastname: Cohn
authors.forename: C
authors.initials: C
authors.lastname: Lanni
authors.forename: H
authors.initials: H
authors.lastname: Pearlman
authors.forename: P
authors.initials: P
authors.lastname: Karahalios
authors.forename: J M
authors.initials: JM
authors.lastname: Drazen
mesh_terms: D000328:Adult; D000420:Albuterol / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology / Q000652:urine; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017999:Leukotriene E4 / Q000652:urine; D016859:Lipoxygenase Inhibitors; D008297:Male; D016037:Single-Blind Method
chemical_list: D016859:Lipoxygenase Inhibitors; D017999:Leukotriene E4; D000420:Albuterol; C063449:zileuton; D006918:Hydroxyurea