Greiff L, Persson C G, Svensson C, Enander I, Andersson M
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
J Allergy Clin Immunol. 1995 Jul;96(1):97-103. doi: 10.1016/s0091-6749(95)70038-2.
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).
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.
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.
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.
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).
尽管抗组胺药在过敏性鼻炎治疗中广泛应用，但对于这些药物对气道黏膜指标的影响却知之甚少，这些指标能特异性反映肥大细胞释放活性（类胰蛋白酶）或大量血浆的微血管 - 上皮渗出（α2 - 巨球蛋白）。
本研究纳入季节性过敏性鼻炎患者，探讨氯雷他定治疗对变应原诱导的鼻黏膜类胰蛋白酶和α2 - 巨球蛋白分泌的影响。同时也研究其对鼻部症状和嗜酸性粒细胞的影响。
安慰剂和氯雷他定（20毫克）每日口服1次，共5天，间隔6周重复。在第5天进行鼻腔稀释液和变应原激发试验。每次激发后用盐溶液冲洗鼻腔黏膜，测定鼻冲洗液中类胰蛋白酶和α2 - 巨球蛋白水平。对鼻部症状进行评分，并测量鼻呼气峰流速。在变应原激发试验前及激发后24小时，用刷取装置获取表层细胞（嗜酸性粒细胞）。
变应原剂量依赖性地增加鼻部症状以及α2 - 巨球蛋白和类胰蛋白酶的冲洗液水平。变应原还降低了鼻呼气峰流速。氯雷他定抑制α2 - 巨球蛋白的渗出，降低类胰蛋白酶水平、鼻部症状和鼻塞，但不影响嗜酸性粒细胞数量。
氯雷他定对鼻冲洗液中α2 - 巨球蛋白水平的抑制作用表明，组胺通过作用于微血管H1受体，介导急性过敏性鼻炎中变应原激发诱导的大量血浆渗出。冲洗液中类胰蛋白酶水平降低表明，氯雷他定要么直接减弱肥大细胞释放活性，要么通过抑制渗出过程，单纯减弱组织溶质（在本病例中为类胰蛋白酶）的腔内进入。
