ORIGINAL ARTICLESEffect of cysteinyl-leukotriene receptor antagonist ICI 204.219 on allergen-induced bronchoconstriction and airway hyperreactivity in atopic subjects
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Proinflammatory Pathways in the Pathogenesis of Asthma
2019, Clinics in Chest MedicineCitation Excerpt :Most of the clinical trials examining the therapeutic effect of LTs in asthma and allergic diseases have been in this class of medications and confirmed that cysteinyl LTs contributed a major portion of the bronchospasm that resulted from allergen challenge. Administration of the cysLT1 antagonist zafirlukast before allergen challenge inhibited immediate-phase bronchospasm by approximately 80% and reduced the late phase by 50%.175,176 CysLT1 antagonists and 5-LO inhibitors blunted the influx of airway inflammatory cells after segmental allergen challenge.177,178
Mast cells in airway diseases and interstitial lung disease
2016, European Journal of PharmacologyCitation Excerpt :Mast cell-derived mediators induce the classical features of the early asthmatic reaction in vivo, inducing bronchoconstriction, mucus secretion and mucosal oedema (for reviews see Bradding and Cruse (2008), Bradding et al. (2006), Brightling et al. (2003a) and Moiseeva and Bradding (2011)). For example, several studies have identified an increase in histamine, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) in the BAL fluid of asthma subjects following bronchial allergen challenge (Casale et al., 1987; Liu et al., 1991; Murray et al., 1986; Sedgwick et al., 1991; Wenzel et al., 1988, 1990, 1991) and that the early asthmatic reaction is significantly alleviated with the administration of potent selective inhibitors of histamine, LTC4 and to a lesser extent PGD2 (Beasley et al., 1987; Curzen et al., 1987; Findlay et al., 1992; Rafferty et al., 1987; Taylor et al., 1991). These mediators are most likely derived from mast cells in the bronchial mucosa because histamine, PGD2 and LTC4 are all released from human lung mast cells in vitro with remarkably similar kinetics to the allergen challenge studies (Schleimer et al., 1986).
Emerging concepts: mast cell involvement in allergic diseases
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