BACKGROUND: Despite the wide use of antihistamines in the treatment of allergic rhinitis, little is known about effects of these drugs on airway mucosal indices, which specifically reflect either mast cell release activity (tryptase) or microvascular-epithelial exudation of bulk plasma (alpha 2-macroglobulin). OBJECTIVE: This study, involving subjects with seasonal allergic rhinitis, examines the effects of loratadine treatment on allergen-induced nasal mucosal output of tryptase and alpha 2-macroglobulin. Effects on nasal symptoms and eosinophils are also examined. METHODS:Placebo and loratadine (20 mg) were given orally once daily for 5 days at 6-week intervals. Nasal diluent and allergen challenges were carried out on day 5. The mucosa was lavaged with saline solution after each challenge, and nasal lavage fluid levels of tryptase and alpha 2-macroglobulin were determined. Nasal symptoms were scored, and nasal peak expiratory flow rates were measured. Superficial cells (eosinophils) were obtained with a brush device before and 24 hours after the allergen challenges. RESULTS: Allergen dose-dependently increased the nasal symptoms and the lavage fluid levels of alpha 2-macroglobulin and tryptase. Allergen also reduced the nasal peak expiratory flow rates. Loratadine inhibited the exudation of alpha 2-macroglobulin and reduced tryptase levels, nasal symptoms, and obstruction, but did not affect the number of eosinophils. CONCLUSION: The inhibitory effects of loratadine on nasal lavage fluid levels of alpha 2-macroglobulin suggest that histamine, through effects on microvascular H1-receptors, mediates allergen challenge-induced exudation of bulk plasma in acute allergic rhinitis. The reduced lavage fluid levels of tryptase suggest either that loratadine directly attenuates mast cell release activity or that loratadine, through inhibition of the exudation process, simply attenuates luminal entry of tissue solutes (in this case, tryptase).
RCT Entities:
BACKGROUND: Despite the wide use of antihistamines in the treatment of allergic rhinitis, little is known about effects of these drugs on airway mucosal indices, which specifically reflect either mast cell release activity (tryptase) or microvascular-epithelial exudation of bulk plasma (alpha 2-macroglobulin). OBJECTIVE: This study, involving subjects with seasonal allergic rhinitis, examines the effects of loratadine treatment on allergen-induced nasal mucosal output of tryptase and alpha 2-macroglobulin. Effects on nasal symptoms and eosinophils are also examined. METHODS: Placebo and loratadine (20 mg) were given orally once daily for 5 days at 6-week intervals. Nasal diluent and allergen challenges were carried out on day 5. The mucosa was lavaged with saline solution after each challenge, and nasal lavage fluid levels of tryptase and alpha 2-macroglobulin were determined. Nasal symptoms were scored, and nasal peak expiratory flow rates were measured. Superficial cells (eosinophils) were obtained with a brush device before and 24 hours after the allergen challenges. RESULTS: Allergen dose-dependently increased the nasal symptoms and the lavage fluid levels of alpha 2-macroglobulin and tryptase. Allergen also reduced the nasal peak expiratory flow rates. Loratadine inhibited the exudation of alpha 2-macroglobulin and reduced tryptase levels, nasal symptoms, and obstruction, but did not affect the number of eosinophils. CONCLUSION: The inhibitory effects of loratadine on nasal lavage fluid levels of alpha 2-macroglobulin suggest that histamine, through effects on microvascular H1-receptors, mediates allergen challenge-induced exudation of bulk plasma in acute allergic rhinitis. The reduced lavage fluid levels of tryptase suggest either that loratadine directly attenuates mast cell release activity or that loratadine, through inhibition of the exudation process, simply attenuates luminal entry of tissue solutes (in this case, tryptase).
Authors: G M Walsh; L Annunziato; N Frossard; K Knol; S Levander; J M Nicolas; M Taglialatela; M D Tharp; J P Tillement; H Timmerman Journal: Drugs Date: 2001 Impact factor: 9.546