The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma

Elliot Israel, Paul Rubin, James P. Kemp, Jay Grossman, William Pierson, Sheldon C. Siegel, David Tinkelman, John J. Murray, William Busse, Allen T. Segal, James Fish, Harold B. Kaiser, Dennis Ledford, Sally Wenzel, Richard R Rosenthal, Judith Cohn, Carmine Lanni, Helene Pearlman, Peter Karahalios, Jeffrey M. Drazen

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)1059-1066
Number of pages8
JournalAnnals of Internal Medicine
Volume119
Issue number11
StatePublished - Dec 1 1993
Externally publishedYes

Fingerprint

zileuton
Arachidonate 5-Lipoxygenase
Asthma
Creatinine
Forced Expiratory Volume
Placebos
Leukotriene E4
Lipoxygenase Inhibitors
Airway Obstruction
Therapeutics
Double-Blind Method
Hypersensitivity
Steroids
Lung

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Israel, E., Rubin, P., Kemp, J. P., Grossman, J., Pierson, W., Siegel, S. C., ... Drazen, J. M. (1993). The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Annals of Internal Medicine, 119(11), 1059-1066.

The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. / Israel, Elliot; Rubin, Paul; Kemp, James P.; Grossman, Jay; Pierson, William; Siegel, Sheldon C.; Tinkelman, David; Murray, John J.; Busse, William; Segal, Allen T.; Fish, James; Kaiser, Harold B.; Ledford, Dennis; Wenzel, Sally; Rosenthal, Richard R; Cohn, Judith; Lanni, Carmine; Pearlman, Helene; Karahalios, Peter; Drazen, Jeffrey M.

In: Annals of Internal Medicine, Vol. 119, No. 11, 01.12.1993, p. 1059-1066.

Research output: Contribution to journalArticle

Israel, E, Rubin, P, Kemp, JP, Grossman, J, Pierson, W, Siegel, SC, Tinkelman, D, Murray, JJ, Busse, W, Segal, AT, Fish, J, Kaiser, HB, Ledford, D, Wenzel, S, Rosenthal, RR, Cohn, J, Lanni, C, Pearlman, H, Karahalios, P & Drazen, JM 1993, 'The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma', Annals of Internal Medicine, vol. 119, no. 11, pp. 1059-1066.
Israel E, Rubin P, Kemp JP, Grossman J, Pierson W, Siegel SC et al. The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Annals of Internal Medicine. 1993 Dec 1;119(11):1059-1066.
Israel, Elliot ; Rubin, Paul ; Kemp, James P. ; Grossman, Jay ; Pierson, William ; Siegel, Sheldon C. ; Tinkelman, David ; Murray, John J. ; Busse, William ; Segal, Allen T. ; Fish, James ; Kaiser, Harold B. ; Ledford, Dennis ; Wenzel, Sally ; Rosenthal, Richard R ; Cohn, Judith ; Lanni, Carmine ; Pearlman, Helene ; Karahalios, Peter ; Drazen, Jeffrey M. / The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. In: Annals of Internal Medicine. 1993 ; Vol. 119, No. 11. pp. 1059-1066.
@article{e626347be8024df99be2a74c379d3d88,
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. 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.",
author = "Elliot Israel and Paul Rubin and Kemp, {James P.} and Jay Grossman and William Pierson and Siegel, {Sheldon C.} and David Tinkelman and Murray, {John J.} and William Busse and Segal, {Allen T.} and James Fish and Kaiser, {Harold B.} and Dennis Ledford and Sally Wenzel and Rosenthal, {Richard R} and Judith Cohn and Carmine Lanni and Helene Pearlman and Peter Karahalios and Drazen, {Jeffrey M.}",
year = "1993",
month = "12",
day = "1",
language = "English (US)",
volume = "119",
pages = "1059--1066",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
number = "11",

}

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 R

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.

UR - http://www.scopus.com/inward/record.url?scp=0027369276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027369276&partnerID=8YFLogxK

M3 - Article

VL - 119

SP - 1059

EP - 1066

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 11

ER -