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* Slide 10 ?LTD4 has also been shown to play a role in nasal secretion (rhinorrhea) in patients with allergic rhinitis. While the average amount of secretion was less with LTD4 (0.28 ± 0.36 g with a threshold concentration of 2 ? 10–1.4 μg/ml) than with antigen or histamine, the duration of nasal secreation was comparable to that with topical antigen and longer than that observed with histamine.17 Ref 17,p 538, Table 2, C2, ?2, L1-8; p 539, C2, ?1, L16-22, C3, L1-2 * Slide 8 Key question number 1 in applying the principles of Dale’s postulates to the role of cysteinyl leukotrienes in allergic rhinitis can be answered affirmatively. Clinical data show that cysteinyl leukotrienes are recovered at increased concentrations in patients with allergic rhinitis. Furthermore, concentrations of cysteinyl leukotrienes increase as symptom severity increases. In a clinical study of 17 subjects allergic to ragweed, mean cysteinyl leukotriene concentrations in nasal secretions rose after allergen challenge with 10, 100, 1000, and 5000 grains of ragweed pollen.20 In another study of 16 children (5 to 12 years of age) with allergic rhinitis and ragweed sensitivity, nasopharyngeal secretions were measured at baseline, during peak ragweed exposure, and two weeks after the end of the ragweed season. Individual LTC4 concentrations in these children increased up to sixfold during the peak season versus pre-season baseline. Mean LTC4 in the study population as a whole also increased significantly during peak (p0.001 vs. baseline). Increased LTC4 concentrations were often correlated with symptoms.28 The following slides provide an answer to key question number 2. Ref 20, p 1627, C1, ?4, L7-11, C2, ?4, L6-8; p 1628, Fig 1 Ref 28, p 414, C2, ?1, L1-13; p 415, C1, ?1, L2-7; p 416, C1, L1-12, ?1, L1-9 * Slide 14 A multicenter, randomized, double-blind, placebo-controlled trial compared the cysteinyl leukotriene antagonist montelukast to placebo in patients with seasonal al
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