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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4 Pt 1
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pubmed:dateCreated |
1995-11-1
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pubmed:abstractText |
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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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1073-449X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
152
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1203-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:7551371-Adult,
pubmed-meshheading:7551371-Arachidonate 5-Lipoxygenase,
pubmed-meshheading:7551371-Asthma,
pubmed-meshheading:7551371-Bronchial Hyperreactivity,
pubmed-meshheading:7551371-Bronchial Provocation Tests,
pubmed-meshheading:7551371-Cold Temperature,
pubmed-meshheading:7551371-Double-Blind Method,
pubmed-meshheading:7551371-Female,
pubmed-meshheading:7551371-Forced Expiratory Volume,
pubmed-meshheading:7551371-Humans,
pubmed-meshheading:7551371-Hydroxyurea,
pubmed-meshheading:7551371-Lipoxygenase Inhibitors,
pubmed-meshheading:7551371-Male,
pubmed-meshheading:7551371-Single-Blind Method,
pubmed-meshheading:7551371-Time Factors
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pubmed:year |
1995
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pubmed:articleTitle |
Effect of chronic 5-lipoxygenase inhibition on airway hyperresponsiveness in asthmatic subjects.
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pubmed:affiliation |
Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't,
Multicenter Study
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