{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:02:13Z","timestamp":1774688533952,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1995,10,1]],"date-time":"1995-10-01T00:00:00Z","timestamp":812505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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)<\/jats:p>","DOI":"10.1164\/ajrccm.152.4.7551371","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T17:53:17Z","timestamp":1365097997000},"page":"1203-1207","source":"Crossref","is-referenced-by-count":61,"title":["Effect of Chronic 5-Lipoxygenase Inhibition on Airway Hyperresponsiveness in Asthmatic Subjects"],"prefix":"10.1093","volume":"152","author":[{"given":"A R","family":"Fischer","sequence":"first","affiliation":[{"name":"Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C A","family":"McFadden","sequence":"additional","affiliation":[{"name":"Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Frantz","sequence":"additional","affiliation":[{"name":"Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W M","family":"Awni","sequence":"additional","affiliation":[{"name":"Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Cohn","sequence":"additional","affiliation":[{"name":"Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J M","family":"Drazen","sequence":"additional","affiliation":[{"name":"Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Israel","sequence":"additional","affiliation":[{"name":"Combined Program in Pulmonary and Critical Care Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1995,10,1]]},"container-title":["American journal of respiratory and critical care medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/152\/4\/1203\/67626723\/ajrccm_152_4_1203.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/152\/4\/1203\/67626723\/ajrccm_152_4_1203.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:29:59Z","timestamp":1774686599000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/152\/4\/1203\/8553715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,10,1]]},"references-count":0,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1995,10,1]]},"published-print":{"date-parts":[[1995,10,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.152.4.7551371","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1995,10]]},"published":{"date-parts":[[1995,10,1]]}}}