{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:30:48Z","timestamp":1785234648207,"version":"3.55.0"},"reference-count":121,"publisher":"American Academy of Pediatrics (AAP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,2,1]]},"abstract":"<jats:p>Cysteinyl leukotrienes (Cys-LTs) are mediators released in asthma and virus-induced wheezing. Corticosteroids appear to have little or no effect on this release in vivo. Cys-LTs are both direct bronchoconstrictors and proinflammatory substances that mediate several steps in the pathophysiology of chronic asthma, including inflammatory cell recruitment, vascular leakage, and possibly airway remodeling. Blocking studies show that Cys-LTs are pivotal mediators in the pathophysiology of asthma. Cys-LTs are key components in the early and late allergic airway response and also contribute to bronchial obstruction after exercise and hyperventilation of cold, dry air in asthmatics. LT modifiers reduce airway eosinophil numbers and exhaled nitric oxide levels. Together these findings support an important role for the Cys-LTs in the asthma airway inflammation. Cys-LT receptor antagonists (Cys-LTRA) are generally well-tolerated. Phase III randomized, controlled clinical trials (RCT) show that LT modifiers are moderately effective, apparently with a particular between-patient variability in their clinical response. The clinical effects of LT modifiers are additive to those of \u03b2-agonists and corticosteroids. The onset of action of LT modifiers is within 1 to several days, and not rapid enough to make them useful as rescue treatment. Although LT modifiers possess some antiinflammatory activity, they cannot substitute for corticosteroids for inflammation control. LT modifiers are alternatives to long-acting \u03b2-agonists as complementary treatment to inhaled corticosteroids in pediatric asthma management because they provide bronchodilation and bronchoprotection without development of tolerance, and complement the antiinflammatory activity unchecked by steroids. In addition, the Cys-LTRA montelukast has been shown to ameliorate asthmatic symptoms and provide bronchoprotection in asthmatic preschool children from 2 years of age, which is of particular importance in this difficult-to-manage group of asthmatics. Given their efficacy, antiinflammatory activity, oral administration, and safety, LT modifiers will play an important role in the treatment of asthmatic children.<\/jats:p>","DOI":"10.1542\/peds.107.2.381","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:55:51Z","timestamp":1092441351000},"page":"381-390","source":"Crossref","is-referenced-by-count":67,"title":["Leukotriene Modifiers in Pediatric Asthma Management"],"prefix":"10.1542","volume":"107","author":[{"given":"Hans","family":"Bisgaard","sequence":"first","affiliation":[{"name":"1 From the Department of Paediatrics, Copenhagen University Hospital, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2001,2,1]]},"reference":[{"key":"2021121009481493400_B1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/21658","article-title":"Characterization of the human cysteinyl leukotriene CysLT1 receptor.","volume":"399","author":"Lynch","year":"1999","journal-title":"Nature."},{"key":"2021121009481493400_B2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1159\/000235025","article-title":"Enhanced leukotriene C4 production by peripheral eosinophilic granulocytes from children with asthma.","volume":"90","author":"Schauer","year":"1989","journal-title":"Int Arch Allergy Appl Immunol."},{"key":"2021121009481493400_B3","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-2125.1992.tb04062.x","article-title":"Enhanced leukotriene synthesis in leukocytes of atopic and asthmatic subjects.","volume":"33","author":"Sampson","year":"1992","journal-title":"Br J Clin Pharmacol."},{"key":"2021121009481493400_B4","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1164\/ajrccm.152.3.7663802","article-title":"Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma.","volume":"152","author":"Wenzel","year":"1995","journal-title":"Am J Respir Crit Care Med."},{"key":"2021121009481493400_B5","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/j.1398-9995.1997.tb02606.x","article-title":"Leukotriene E4 plasma levels in adult asthmatic patients with variable disease severity.","volume":"52","author":"Chavis","year":"1997","journal-title":"Allergy."},{"key":"2021121009481493400_B6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1136\/adc.73.3.221","article-title":"Persistent increase in plasma and urinary leukotrienes after acute asthma.","volume":"73","author":"Sampson","year":"1995","journal-title":"Arch Dis Child."},{"key":"2021121009481493400_B7","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0091-6749(05)80068-5","article-title":"Urinary leukotriene E4 levels during early and late asthmatic responses.","volume":"86","author":"Manning","year":"1990","journal-title":"J Allergy Clin Immunol."},{"key":"2021121009481493400_B8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1164\/ajrccm\/146.1.96","article-title":"Urinary excretion of leukotriene E 4 and 11-dehydro-thromboxane B2 in response to bronchial provocations with allergen, aspirin, leukotriene D4, and histamine in asthmatics.","volume":"146","author":"Kumlin","year":"1992","journal-title":"Am Rev Respir Dis."},{"key":"2021121009481493400_B9","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/0091-6749(92)90294-C","article-title":"Urinary leukotriene E4 after exercise challenge in children with asthma.","volume":"89","author":"Kikawa","year":"1992","journal-title":"J Allergy Clin Immunol."},{"key":"2021121009481493400_B10","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1136\/thx.52.12.1030","article-title":"Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist.","volume":"52","author":"Reiss","year":"1997","journal-title":"Thorax."},{"key":"2021121009481493400_B11","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1164\/ajrccm.152.4.7551372","article-title":"Enhanced arachidonic acid metabolism in alveolar macrophages from wheezy infants. 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