Davies R J, Bagnall A C, McCabe R N, Calderon M A, Wang J H
Department of Respiratory Medicine and Allergy, St Bartholomew's Hospital, London, UK.
Clin Exp Allergy. 1996 May;26 Suppl 3:11-7. doi: 10.1111/j.1365-2222.1996.tb00653.x.
The pathogenesis of allergic rhinitis is complex, involving not only histamine and mast cell-derived tryptase, but also eosinophil- and neutrophil-derived mediators, cytokines, and intercellular cell adhesion molecules (ICAM-1). It is surprising that antihistamines, which block only one component of the process, have proved so effective in the management of allergic rhinitis. Research has therefore focused on whether antihistamines have additional pharmacological activities. In vitro studies have shown that high concentrations of second generation antihistamines can block inflammatory mediator release from basophils and mast cells, and reduce ICAM-1 expression in epithelial cell lines. In vivo studies have also shown an effect on the allergen-induced inflammatory reaction; both oral and intranasal antihistamines cause a reduction in nasal symptoms and inflammatory cell influx. Oral terfenadine and cetirizine and intranasal levocabastine and azelastine have also demonstrated a lowering of ICAM-1 expression on epithelial cells. With regard to clinical efficacy, topical levocabastine (0.5 mg/mL eye drop solution and 0.5 mg/mL nasal spray) was shown to be more effective than oral terfenadine (60 mg twice daily) in relieving ocular itch (P = 0.02) and reducing nasal symptoms in allergic rhinoconjunctivitis. In a further study, levocabastine eye drops were as effective and well tolerated as sodium cromoglycate in seasonal allergic rhinitis. Intranasal azelastine (0.28 mg twice daily) showed a trend for superior relief of rhinorrhoea and nasal obstruction compared with oral terfenadine (60 mg twice daily). In addition, intranasal azelastine (0.28 mg twice daily) resulted in significant reductions in sneezing, nasal obstruction, rhinorrhoea and itching in perennial rhinitis, compared with the lower efficacy of beclomethasone dipropionate (0.1 mg twice daily). As well as benefits in efficacy, topical administration is associated with improved safety. Some antihistamines, particularly those metabolized in the liver, are associated with occasional reports of severe side-effects. It is therefore logical to administer antihistamines directly to the target organ.
变应性鼻炎的发病机制复杂，不仅涉及组胺和肥大细胞源性类胰蛋白酶，还涉及嗜酸性粒细胞和中性粒细胞源性介质、细胞因子以及细胞间黏附分子（ICAM - 1）。令人惊讶的是，仅阻断该过程中一个成分的抗组胺药在变应性鼻炎的治疗中已被证明如此有效。因此，研究集中在抗组胺药是否具有其他药理活性。体外研究表明，高浓度的第二代抗组胺药可阻断嗜碱性粒细胞和肥大细胞释放炎性介质，并降低上皮细胞系中ICAM - 1的表达。体内研究也显示了对变应原诱导的炎症反应有影响；口服和鼻用抗组胺药均可减轻鼻部症状和炎性细胞浸润。口服特非那定和西替利嗪以及鼻用左卡巴斯汀和氮卓斯汀也已证明可降低上皮细胞上ICAM - 1的表达。关于临床疗效，局部用左卡巴斯汀（0.5 mg/mL滴眼液和0.5 mg/mL鼻喷雾剂）在缓解眼部瘙痒（P = 0.02）和减轻变应性鼻结膜炎的鼻部症状方面比口服特非那定（60 mg，每日两次）更有效。在另一项研究中，左卡巴斯汀滴眼液在季节性变应性鼻炎中的疗效与色甘酸钠相当且耐受性良好。与口服特非那定（60 mg，每日两次）相比，鼻用氮卓斯汀（0.28 mg，每日两次）在缓解鼻漏和鼻塞方面有更优趋势。此外，与二丙酸倍氯米松（0.1 mg，每日两次）较低的疗效相比，鼻用氮卓斯汀（0.28 mg，每日两次）可显著减轻常年性鼻炎中的打喷嚏、鼻塞、鼻漏和瘙痒。除了疗效方面的益处外，局部给药还与安全性提高相关。一些抗组胺药，尤其是那些在肝脏中代谢的药物，偶尔会有严重副作用的报道。因此，将抗组胺药直接给药至靶器官是合理的。
