| Effect of chronic 5-lipoxygenase inhibition on airway hyperresponsiveness in asthmatic subjects. | |
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MedLine Citation:
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PMID: 7551371 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The leukotrienes are known bronchoactive agonists with potential proinflammatory effects that may be involved in mediating airway hyperresponsiveness. We investigated the effects of zileuton, an inhibitor of 5-lipoxygenase (5-LO), on airway responsiveness to cold, dry air in patients with moderate asthma. A group of 10 asthmatic patients underwent cold, dry air hyperventilation challenge; challenges were performed before drug treatment and 1 to 10 d after the completion of treatment with study drugs. The cold air minute ventilation required to cause a 15% decrease in FEV1 (PD15 VE) increased by 58% compared with the response before treatment, 1 to 10 d after the completion of 13 wk of treatment with zileuton. The geometric mean (geometric mean/SEM and geometric mean x SEM) PD15 VE increased from 24.5 (20.4, 29.5) L/min to 38.8 (34.7, 43.7) L/min (p = 0.01). Zileuton treatment inhibited 5-LO as measured ex vivo by ionophore-stimulated LTB4 levels in whole blood. In four of seven subjects, LTB4 levels before zileuton ingestion fell from 110.88 +/- 25.42 to 5.40 +/- 1.95 ng/ml 2 h post-zileuton dosing (p = 0.02, pre- versus 2 h postzileuton ingestion). Consistent with the short half-life of zileuton, 6 h postzileuton dosing the ionophore-stimulated, LTB4 levels in whole blood had increased to 89.68 +/- 35.54 ng/ml (p = 0.41, pre- versus 6 h postzileuton ingestion). Based on the first-order kinetics of zileuton, its effect on 5-LO activity should have been dissipated less than 16 h postingestion. Thus, chronic zileuton treatment decreased airway hyperresponsiveness as determined by reactivity to cold, dry air.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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A R Fischer; C A McFadden; R Frantz; W M Awni; J Cohn; J M Drazen; E Israel |
Publication Detail:
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Type: Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 152 ISSN: 1073-449X ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 1995 Oct |
Date Detail:
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Created Date: 1995-11-01 Completed Date: 1995-11-01 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1203-7 Citation Subset: AIM; IM |
Affiliation:
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Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Arachidonate 5-Lipoxygenase / antagonists & inhibitors*, physiology* Asthma / drug therapy, physiopathology* Bronchial Hyperreactivity / drug therapy, physiopathology* Bronchial Provocation Tests Cold Temperature / diagnostic use Double-Blind Method Female Forced Expiratory Volume Humans Hydroxyurea / analogs & derivatives*, pharmacology Lipoxygenase Inhibitors / pharmacology* Male Single-Blind Method Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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HL-T32-07633/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lipoxygenase Inhibitors; 127-07-1/Hydroxyurea; 132880-11-6/zileuton; EC 1.13.11.34/Arachidonate 5-Lipoxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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