TY - JOUR
T1 - The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma
AU - Israel, Elliot
AU - Rubin, Paul
AU - Kemp, James P.
AU - Grossman, Jay
AU - Pierson, William
AU - Siegel, Sheldon C.
AU - Tinkelman, David
AU - Murray, John J.
AU - Busse, William
AU - Segal, Allen T.
AU - Fish, James
AU - Kaiser, Harold B.
AU - Ledford, Dennis
AU - Wenzel, Sally
AU - Rosenthal, Richard
AU - Cohn, Judith
AU - Lanni, Carmine
AU - Pearlman, Helene
AU - Karahalios, Peter
AU - Drazen, Jeffrey M.
PY - 1993/12/1
Y1 - 1993/12/1
N2 - 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. Design: Randomized, double-blind, placebocontrolled study. Setting: University hospitals and private allergy and pulmonary practices. Patients: 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. Intervention: Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks. Measurements: Airway function, β-agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4). Results: Zileuton produced a 0.35-L (95% Cl, 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 (Cl, 0.16 to 0.48 L), a 13.4% increase, compared with a 0.05-L (Cl, -0.10 to 0.20 L) increase in patients taking placebo (P = 0.02). Symptoms and frequency of β-agonist use also decreased with zileuton, 2.4 g/d. The mean urinary LTE4 level decreased by 39.2 pg/mg creatinine (Cl, 18.1 to 60.4 pg/mg creatinine) and 26.5 pg/mg creatinine (Cl, 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.
AB - 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. Design: Randomized, double-blind, placebocontrolled study. Setting: University hospitals and private allergy and pulmonary practices. Patients: 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. Intervention: Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks. Measurements: Airway function, β-agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4). Results: Zileuton produced a 0.35-L (95% Cl, 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 (Cl, 0.16 to 0.48 L), a 13.4% increase, compared with a 0.05-L (Cl, -0.10 to 0.20 L) increase in patients taking placebo (P = 0.02). Symptoms and frequency of β-agonist use also decreased with zileuton, 2.4 g/d. The mean urinary LTE4 level decreased by 39.2 pg/mg creatinine (Cl, 18.1 to 60.4 pg/mg creatinine) and 26.5 pg/mg creatinine (Cl, 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.
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M3 - Article
C2 - 8239223
AN - SCOPUS:0027369276
SN - 0003-4819
VL - 119
SP - 1059
EP - 1066
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 11
ER -