Asthma Symptoms

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Leukotrienes and Asthma

Leukotrienes play an important role in the pathophysiology of asthma.8

Leukotrienes Role in Asthma Animation

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Origin of inflammatory cells and mediators

Myeloid stem cells, which originate in the bone marrow, differentiate into several inflammatory cell types that are released into the bloodstream. Many of these inflammatory cells have leukotriene receptor sites and produce leukotrienes as well.

Ex vivo studies in current literature suggest that leukotrienes modulate eosinophil activity

CysLTs act as chemoattractants for eosinophils:9–14

  • Enhancing recruitment of inflammatory mediators
    In an ex vivo study of eosinophils from subjects with atopic asthma, CysLTs enhanced eosinophil recruitment.12
  • Upregulation of adhesion molecules
    In an ex vivo study of blood eosinophils, LTD4 upregulated the adhesive property of eosinophils.13
  • Promote migration of eosinophils into airway
    In an ex vivo study of eosinophils from subjects with atopic asthma, CysLTs promoted migration of eosinophils.12
  • Enhance survival of eosinophils
    When eosinophils isolated from subjects with atopic asthma were incubated with LTC4 or LTD4, their survival was significantly enhanced.10

Leukotrienes are potent bronchoconstrictors

Characteristics of healthy bronchi are:

  • Normal cellular activity
  • Normal mucus secretion
  • Intact epithelial layer
  • Open airways

Leukotrienes mediate airway smooth muscle contraction and proliferation resulting in bronchoconstriction, as evidenced by airway narrowing.

  • Bronchoconstriction can be initiated by triggers that include exercise, cold air, and allergens.16 Sensory nerve exposure can contribute to increased bronchial hyperreactivity manifested by cough or wheeze.

SINGULAIR is indicated for prophylaxis and chronic treatment of asthma in patients aged 12 months and older and for prevention of exercise-induced bronchoconstriction (EIB) in patients aged 15 years and older.

For prevention of EIB, a single dose of SINGULAIR should be taken at least 2 hours before exercise. An additional dose of SINGULAIR should not be taken within 24 hours of a previous dose.

Patients already taking 1 tablet daily for another indication should not take an additional dose to prevent EIB.

SELECTED SAFETY INFORMATION

  • SINGULAIR should not be used as rescue medication to treat acute asthma episodes. Patients should be advised to have appropriate rescue medication available.
  • Neuropsychiatric events have been reported in patients taking SINGULAIR. These events included agitation, aggressive behavior or hostility, anxiousness, depression, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor. The clinical details of some postmarketing reports appear consistent with a drug-induced effect. Patients should be advised to report any neuropsychiatric events.
  • Use of SINGULAIR may not eliminate the need for inhaled or systemic corticosteroids. Patients should not decrease the dose or stop taking any other antiasthma medications unless instructed by a physician.
  • Safety and effectiveness of SINGULAIR in patients younger than 12 months with asthma have not been established.

Before prescribing SINGULAIR, please read the Prescribing Information.

See all references.

20951836(5)-02/10-SNG

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