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上呼吸道疾病与变应原免疫疗法的进展

Advances in upper airway diseases and allergen immunotherapy.

作者信息

Nelson Harold S

机构信息

National Jewish Medical and Research Center, Denver, Colorado 80206, USA.

出版信息

J Allergy Clin Immunol. 2006 May;117(5):1047-53. doi: 10.1016/j.jaci.2005.12.1306. Epub 2006 Mar 6.

Abstract

The purpose of this review is to highlight important articles on upper airway disease and immunotherapy that appeared in the Journal of Allergy and Clinical Immunology and elsewhere during 2005. In recent studies of tissue from patients with chronic hypertrophic eosinophilic sinusitis, increased leukotriene C4 synthase and 5-lipoxygenase activity and increased levels of cysteinyl leukotriene production were demonstrated that correlated with disease severity but not with whether the patient was aspirin sensitive. However, the cysteinyl leukotriene 1 receptor was increased in leukocytes in the sinus tissue only in those patients with aspirin sensitivity. Major basic protein, released by eosinophils into the mucus in the paranasal sinus lumen, was found to reach concentrations capable of damaging the sinus epithelium, predisposing to bacterial infections. Testing the hypothesis that chronic hypertrophic eosinophilic sinusitis represents a reaction to common fungi, a double-blind trial of intranasal instillation of amphotericin B was conducted. There were marginal but significant differences in favor of amphotericin B treatment for sinus mucosal thickening on the basis of computed tomography and the evidence of eosinophilic inflammation in the sinus mucus. The effectiveness of topical nasal corticosteroids for treatment of nasal polyps was confirmed in 2 large studies. Improvement in sleep quality and daytime drowsiness in patients with allergic rhinitis treated with nasal corticosteroids was reported to correlate with reduction in nasal obstruction. The statistical analysis behind studies that reported a decrease in asthma exacerbations with nasal corticosteroids or oral antihistamines has been questioned. It appears that the results of at least one of these studies are indeed too good to be true. Although caution is still indicated in administering immunotherapy to patients receiving beta-adrenergic blocking agents, the prohibition might not be absolute. A study in patients with Hymenoptera sensitivity given venom immunotherapy revealed no increase in serious adverse reactions to venom injections and no greater incidence of reactions to insect stings in those taking beta-blocking agents. Sublingual immunotherapy for 8 to 12 weeks in patients with hazelnut sensitivity significantly increased their tolerance to hazelnut in double-blind, placebo-controlled challenges while inducing increased IgG4 and IL-10 levels, indicating induction of regulatory T cells. There were a number of articles in the Journal of Allergy and Clinical Immunology in 2005 that addressed the entity of chronic hypertrophic eosinophilic sinusitis. In addition, an update of the "Practice parameters on sinusitis" was published. The major focus in allergen immunotherapy continues to be sublingual administration.

摘要

本综述的目的是重点介绍2005年发表于《过敏与临床免疫学杂志》及其他地方的有关上呼吸道疾病和免疫疗法的重要文章。在最近对慢性肥厚性嗜酸性鼻窦炎患者组织的研究中,发现白三烯C4合酶和5-脂氧合酶活性增加,半胱氨酰白三烯生成水平升高,这些与疾病严重程度相关,但与患者是否对阿司匹林敏感无关。然而,仅在那些对阿司匹林敏感的患者鼻窦组织白细胞中,半胱氨酰白三烯1受体增加。嗜酸性粒细胞释放到鼻窦腔黏液中的主要碱性蛋白,其浓度足以损伤鼻窦上皮,易引发细菌感染。为验证慢性肥厚性嗜酸性鼻窦炎是对常见真菌的一种反应这一假说,进行了一项两性霉素B鼻内滴注的双盲试验。基于计算机断层扫描以及鼻窦黏液中嗜酸性粒细胞炎症的证据,两性霉素B治疗在鼻窦黏膜增厚方面有微小但显著的差异。两项大型研究证实了局部鼻用皮质类固醇治疗鼻息肉的有效性。据报道,接受鼻用皮质类固醇治疗的过敏性鼻炎患者睡眠质量改善和日间嗜睡情况与鼻塞减轻相关。报道使用鼻用皮质类固醇或口服抗组胺药可减少哮喘发作的研究背后的统计分析受到质疑。似乎这些研究中至少有一项的结果好得令人难以置信。尽管在给接受β-肾上腺素能阻滞剂治疗的患者进行免疫治疗时仍需谨慎,但这种禁忌可能并非绝对。一项对接受蜂毒免疫疗法的膜翅目昆虫敏感患者的研究显示,服用β-阻滞剂的患者对蜂毒注射的严重不良反应未增加,对昆虫叮咬的反应发生率也未更高。对榛子敏感患者进行8至12周的舌下免疫疗法,在双盲、安慰剂对照激发试验中显著提高了他们对榛子的耐受性,同时诱导IgG4和IL-10水平升高,表明诱导了调节性T细胞。2005年《过敏与临床免疫学杂志》上有许多文章探讨了慢性肥厚性嗜酸性鼻窦炎这一实体。此外,还发表了“鼻窦炎实践参数”的更新内容。变应原免疫疗法的主要重点仍然是舌下给药。

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