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WAO News & Notes - September 2007
Volume 4, Issue 9

Medical Journal Reviews
医学期刊回顾   20079月(第9期)

Medical Journal Reviews

Reviewed by Mark C. Glaum, MD, PhD and, WAO Guest Editors, Division of Allergy and Immunology, University of South Florida College of Medicine


Mark C. Glaum, MD, PhDGary Hellermann, PhDWAO


1. Risks of inhaled corticosteroids in COPD

Inhaled corticosteroids (ICS) are commonly used to treat COPD, although efficacy in this disease is less clear. A case-control study within a large cohort of Canadian patients with COPD was performed to determine whether ICS use is associated with increased risk of pneumonia. When normalized for COPD severity, ICS use is still associated with a 70% increased risk of hospitalization for pneumonia. With increased doses (fluticasone 1000 mcg per day or equivalent), the risk of hospitalization for pneumonia is 2-fold high than case control subjects. Editor’s comment: Risk for pneumonia should be considered when prescribing ICS in COPD. Ernst P, Gonzales AV, Brassard P, Suissa S. Am J Respir Crit Care Med 2007; 176:162-166.



吸入性皮质激素()被广泛用于治疗慢性阻塞性肺病(COPD),然而其效果还不太清楚。在这个加拿大大型病例对照队列研究中,观察吸入皮质激素治疗慢性阻塞性肺病患者是否会增加患肺炎的危险。将慢性阻塞性肺疾病严重程度进行标准化,结果吸入皮质激素与因肺炎住院相关,吸入激素增加70%肺炎住院风险。用较高剂量皮质激素吸入治疗(氟替卡松1000mcg/天,或同等剂量其他药物),住院肺炎比对照组增高2倍。编者按:在用吸入皮质激素治疗COPD时,应考虑肺炎的风险。Ernst P, Gonzales AV, Brassard P, Suissa S. Am J Respir Crit Care Med 2007; 176:162-166.


2. Polymorphisms in IL-13 are associated with total IgE, eosinophilia and asthma exacerbations

Polymorphisms in the IL-13 gene were examined for association with total serum IgE, eosinophilia and asthma exacerbations in Costa Rican children and in children enrolled in the Childhood Asthma Management Program (CAMP). IL-13 polymorphisms are associated with elevated serum IgE, and eosinophilia, but these polymorphisms are associated with asthma exacerbations in subjects on inhaled corticosteroids only in the CAMP subjects. Editor’s comment: The IL-13 gene may be an important locus that predisposes for certain asthma phenotypes. Hunninghake GM, Soto-Quiros ME, Avila L, et al. J Allergy Clin Immunol 2007; 120:84-90.



对哥斯达黎加儿童和加入儿童哮喘管理计划(CAMP)的哮喘患儿,分别检测白细胞介素13基因多态性,并观察是否与总>IgE、嗜酸性粒细胞浸润和哮喘加重相关。白细胞介素-13基因多态性与血清IgE增高和嗜酸性粒细胞浸润相关,但只有组吸入皮质激素的儿童IL-13基因多态性才与哮喘加重相关。编者按:白细胞介素13基因可能是某些哮喘表型的重要标识。>Hunninghake GM, Soto-Quiros ME, Avila L, et al. J Allergy Clin Immunol 2007; 120:84-90.


3. The search for childhood asthma genes

A genome-wide association scan was performed on DNA from 994 subjects with childhood-onset asthma and from 1243 non-asthmatics. More than one-third of children with asthma diagnosed at age 7 years or less show variations in the expression of the ORMDL3 gene on chromosome 17q21. Although the function of ORMDL3 gene product is not known, the gene codes for an evolutionarily ancient transmembrane protein also found in yeast and other primitive organisms. Editor’s comment: This study provides further evidence supporting the importance of genetic factors in childhood asthma. Moffatt MF, Kabesch M, Liang L, et al. Nature 2007; 448:470-473.



994例儿童哮喘和1 243例非哮喘儿童进行DNA基因组相关扫描。7岁或7岁以下被诊断为哮喘的儿童中,三分之一以上在第17对染色体长臂21带上的ORMD13基因有不同程度的表达。ORMD13基因编码一种进化上很古老的跨膜蛋白,这种蛋白在酵母和其他原始生物也存在,但其具体功能尚不明确。编者按:这项研究提供了进一步的证据支持遗传因素在儿童哮喘的重要性。Moffatt MF, Kabesch M, Liang L, et al. Nature 2007; 448:470-473.


4. Attentuation of allergic contact dermatitis through the endocannabinoid system

The human cannabinoid receptors, CB1 and CB2, are G protein-coupled heterotrimers that bind endocannabinoids as well as exogenous agonists such as tetrahydrocannabinol. Triggers of contact dermatitis are small molecules that penetrate the skin and bind proteins to form haptens. The newly formed haptens are then presented to T lymphocytes by dendritic cells and cause an immune response leading to dermatitis. Mice deficient in CB1 and CB2 (Cnr1-/- and Cnr2-/-) develop an ulcerative dermatitis to nickel that is not seen in the wild type, suggesting that the cannabinoid receptors serve to control the immune response. To test this hypothesis, a model contact allergen, dinitrofluorobenzene (DNFB), which causes contact dermatitis, was applied to wild type mice and Cnr1-/- Cnr2-/- mice. DNFB causes a greater allergic response in cannabinoid receptor-deficient mice compared to normal mice. Stimulation of normal mice with tetrahydrocannabinol, an exogenous cannabinoid that binds to CB1/2, further reduces the DNFB-induced dermatitis. Editor’s comment: Human trials of cannabinoid receptor agonists may determine the efficacy of these compounds in reducing contact dermatitis. Karsak M et al. Science 2007; 316:1494.



人类大麻素受体CB1、CB2是一种G蛋白偶联异三聚体,可以和大麻素以及外源性激动剂,如四氢大麻醇结合。引发接触性皮炎的物质都是小分子,这些小分子可渗入皮肤和蛋白质结合,形成半抗原。新形成的半抗原通过树突状细胞被递呈给淋巴细胞,引起免疫反应,导致皮炎。在CB1和CB2缺陷小鼠(Cnr1- /-和Cnr2-/-),镍可引起溃疡性皮炎,而这种现象在野生型小鼠并不出现,说明大麻素受体的作用是控制免疫反应。为验证这一假说,将接触过敏原二硝基氟苯(DNFB)应用于野生型小鼠和Cnr1-/-Cnr2-/-小鼠,导致接触性皮炎。和正常小鼠相比,二硝基氟苯在大麻素受体基因缺陷小鼠造成更严重的过敏性反应。正常小鼠用四氢大麻酚(一种外源性大麻素,可结合Cb1/2)刺激后可进一步降低DNFB诱发的皮炎。编者按:大麻素受体激动剂的人体试验也许可以确定这些化合物减少接触性皮炎的作用。Karsak M et al. Science 2007; 316:1494.


5. A distinct“itch”receptor in the central nervous system

Chronic pruritus can be a debilitating condition for which there are few effective clinical remedies. Although the sensation of itch is mediated by unmyelinated C fibers, an itch-specific mediator in the central nervous system has yet to be identified-until now. Researchers at Washington University have identified a gastrin-releasing peptide (GRP) expressed in the dorsal horn of the spinal cord in mice that mediates itch sensation through its receptor (GRPR). Mice with a mutated GRPR gene demonstrate reduced scratching behavior in response to pruritic stimuli compared to wild type controls. In addition, direct injection of a GRPR antagonist into spinal CSF inhibits scratching but not pain perception. Editor’s comment: This CNS peptide receptor may represent a novel therapeutic target for the development of anti-pruritic agents. Sun Y, Chen Z. Nature 2007;448:700-703.



慢性瘙痒是一种令人不适的疾病,有效的临床措施有限。虽然痒感觉是由无髓神经c纤维介导的,直到现在,中枢神经系统是否有“痒”的特异性介质仍不明确。华盛顿大学的研究人员已经确定了小鼠背角脊髓中的胃泌素释放肽(GRP)通过其受体(GRPR)介导痒感。与野生型小鼠相比,GRPR基因突变小鼠接触致瘙痒刺激物后搔抓反应减少。此外,向脊髓脑脊液直接注射GRPR拮抗剂可抑制搔抓反应,但不抑制疼痛觉。编者按:这种中枢神经肽受体可能为发展止痒剂提供了新的治疗靶点。Sun Y, Chen Z. Nature 2007;448: 700-703.


6. Relationship between airway narrowing, patchy ventilation and lung mechanics in asthmatics

Defects in asthmatic lung ventilation can be localized to heterogeneous areas (Vdefs) which, if numerous or extensive, may have a serious effect on breathing in asthmatics. In this report, 10 mild to moderate asthmatics are tested before and after bronchoconstriction with methacholine. Positron emission tomography (PET) is used to map the regional defects, while lung function (dynamic resistance and elastance) is measured by oscillatory mechanics. The results are mapped into a 3-dimensional lung model to verify that the location and extent of Vdefs, as determined by PET scans, correspond to changes in airflow. A heterogeneous constriction of the airways outside the major bronchioles was found to be necessary to account for the observed changes in lung function and gas exchange upon methacholine challenge. This high degree of specificity in measuring lung mechanics is brought about through an ingenious combination of PET scanning, oscillatory dynamics and computer modeling. Editor’s comment: This paper points out the importance of continued improvement in technology in the understanding of asthma pathology. Tgavalekos NT et al. Eur Resp J 2007; 29:1174.



哮喘患者肺部通气时,可出现局部通气缺损,也可在不同部位出现多处通气缺损(Vdefs)。如果出现多处或广泛部位出现通气缺损,可能会对呼吸产生严重的影响。在这份报告中,10个轻度至中度哮喘患者在支气管痉挛剂乙酰甲胆碱激发试验之前和之后,用正电子发射断层扫描(PET)测绘区域的缺陷,并用振荡波测定肺功能(动力学阻力和弹性)。研究结果通过PET扫描把气流的变化绘制成三维立体肺模型,以明确Vdefs的位置和程度。除主支气管外,气道结构上的异构对乙酰甲胆碱激发后的肺功能和气体交换的改变是必须的。通过巧妙地把PET扫描、振荡动力学和计算机模拟这三种方式组合在一起,使得肺力学的测定有很高的特异性。编者按:本文指出不断进步的新技术对了解哮喘病理的重要性。Tgavalekos NT et al. Eur Resp J 2007; 29:1174.


7. Irritant skin test reactions to common vaccines

Concern over potential reactions to a vaccine is a common cause for allergy consultation. Skin testing against vaccines may be indicated in certain individuals; however interpretation of test results is complicated by irritant skin reactions. Twenty healthy volunteers with no history of allergy to foods or drugs and without a history of adverse reactions to vaccines were skin tested to 10 common vaccines. Results demonstrate that skin prick testing with vaccines does not cause irritant reactions even at full strength. Intradermal testing is more likely to induce irritant reactions with certain vaccines (influenza, MMR, varicella), particularly when used at full strength. Editor’s comment: This work provides clinicians with useful guidelines for choosing appropriate concentrations for vaccine skin testing. Wood RA, Setse R, Halsey N.  J Allergy Clin Immunol 2007; 120:478-81.



关于疫苗的潜在反应,是经常被患者咨询的问题。在极个别个体可能需要皮肤测试,但当对皮试结果进行解释时,阳性结果却经常容易被疫苗的刺激反应所混淆。20名健康志愿者,无食物过敏或药物过敏史,也无疫苗不良反应史,用10个常见的疫苗进行皮肤测试。结果表明,用疫苗进行皮肤点刺试验,即使用原液并不会引起刺激性反应。而某些疫苗的皮内试验(流行性感冒,三联疫苗,水痘),较有可能引起刺激性反应,尤其是当使用原液时。编者按:这篇文章为临床医生选择适当浓度的疫苗进行皮肤测试提供了有用的指引。Wood RA, Setse R, Halsey N. J Allergy Clin Immunol 2007; 120:478-81.


8. Association of selenium supplementation with diabetes type 2

Vitamin supplements are commonly used by patients to treat a variety of medical conditions. Ob- servational epidemiological studies suggest a protective role for antioxidants, including selenium, against the development of diabetes type 2 (DM2). The role of selenium supplementation on the risk of new onset DM2 was examined utilizing data generated from a randomized double-blinded placebo-controlled study designed to study the effect of selenium supplementation on cancer prevention (Nutritional Prevention of Cancer Trial). Supplementation with selenium 200 mcg daily was associated with an incidence of 12.6 cases of DM2 per 1000 person years vs. 8.4 cases per 1000 person years with placebo, hazzard ratio, 1.55 [95% CI, 1.03 to 2.33], despite normalization for age, sex, BMI and tobacco use during an average follow-up period of 7.7 years. Editor’s comment: Prolonged administration of selenium is not protective against DM2 and may even increase risk for this disease. Stranges S, Marshall J, Natarajan J, et al. Ann Intern Med 2007; 147:217-23.



患者治疗各种医学情况时,常采用维生素补充疗法。流行病学研究显示:抗氧化剂,包括硒,对2型糖尿病(DM2)的发生有保护作用。硒补充剂对新发病的DM2患者的影响数据来自一个随机双盲安慰剂对照研究,该研究主要研究目的是硒补充剂对预防癌症的作用(营养防癌试验)。每天补充硒200 mcg,平均随访时间为7.7年后,DM2的发生率12.6/1000人,而对照组为8.4/1000人,危险系数1.55[95%可信区间:1.03~2.33 ]。该研究对年龄,性别,体重指数和吸烟率进行了标准化。编者按:长期应用硒不能预防2型糖尿病,甚至可能增加风险。Stranges S, Marshall J, Natarajan J, et al. Ann Intern Med 2007; 147:217-23.


9. Th17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/ stat1

The possible role of Th17 cells in the generation of uveitis and scleritis in humans was investigated in a mouse model of experimental autoimmune uveitis (EAU). Scleritis and uveitis are chronic inflammatory ocular diseases that can lead to blindness. The number of Th17 cells and level of IL-17 is elevated in peripheral blood from human uveitis and scleritis patients and this causes an increase in TNF-alpha which could account for the pathology. The authors found that humans have Th17 cells in peripheral blood while mice do not. Blocking IL-17 with IL-17 antibody reduces EAU in mice. IL-27, a member of the IL-12 family of proteins that is expressed in retina, inhibits the expansion of Th17 cells and is upregulated by IFN-gamma. In EAU in mice, the disease increases in severity as the IL-17 level goes up and vice versa. As EAU resolves, IL-17 is reduced while the Th-17 phenotype is replaced by Th1. Editor’s comment: Intervention to reduce the number of Th17 cells in patients with chronic uveitis may ameliorate the pathology. Amadi-Obi A, et al. Nature Medicine 2007; 13:711.



用实验性自身免疫性葡萄膜炎(EAU)的小鼠模型研究Th17细胞对人类葡萄膜炎及巩膜炎的作用。巩膜炎及葡萄膜炎是慢性炎症性眼部疾病,可导致失明。葡萄膜炎及巩膜炎患者外周血Th17细胞数量和IL-17水平升高,从而导致肿瘤坏死因子-α增加,造成病理改变。作者发现,人类周围血中存在Th17细胞,而小鼠却没有。用IL-17抗体阻断IL-17后小鼠EDU减轻。IL-27,白细胞介素12蛋白家族成员之一(在视网膜上有表达),则可阻碍Th17细胞的扩增;而γ-干扰素可上调这一反应。在EDU小鼠体内,IL-17水平上升该疾病变得更为严重,反之亦然。EDU缓解后,IL-17减少,而Th-17表型被Th1所取代。编者按:如果干预措施减少慢性葡萄膜炎患者Th17细胞的数量,病理变化有可能得到改善。Amadi-Obi A, et al. Nature Medicine 2007; 13:711.


10. Flavonoids and related compounds as anti-allergic substances

The role of diet in the etiology of asthma and other diseases with an inflammatory component is highly controversial. Plant-derived flavonoids and polyphenols are among the best-studied groups of dietary compounds shown in various model systems and in some clinical studies to reduce inflammation and allergic responses. This comprehensive review evaluates the extensive literature on flavonoids and the immune response especially with regard to the mechanism of action (e.g., inhibition of IL-4 synthesis) and the structure-function relationships. Numerous examples of the clinical effects of flavonoids on allergic disease, both positive and negative are given. Editor’s comment: The evidence seems to demonstrate a protective anti-inflammatory effect of plant flavonoids that are commonly found in fruits, vegetables and beverages. More extensive clinical studies are needed before specific dietary recommendations can be implemented. Kawai M et al. Allergology Internatl 2007; 56:113.



饮食中的炎症性成分在哮喘和其他疾病中的作用颇具争议。植物源性黄酮和多酚类化合物是其中研究最为充分的。在各种动物模型研究和在一些临床研究中,这些膳食成分可减轻炎症和过敏反应。这篇综述全面评价了黄酮和免疫反应的大量相关文献,尤其注意了其作用机制(如抑制IL-4的合成),以及结构与功能的关系。发现很多总黄酮对过敏性疾病影响的例子,既有正面的也有负面的例子。编者按:植物类黄酮具有保护性的抗炎作用,这种物质通常存在于水果,蔬菜和饮料中。还需进一步的临床研究方能进行特异性饮食建议。Kawai M et al. Allergology Internatl 2007; 56:113.


译者:北京协和医院 文利平   

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世界过敏组织(WAO)网站支持WAO使命。 WAO是全球性资源中心,过敏、哮喘和临床免疫学领域的提倡者,通过全世界过敏和临床免疫学会联盟推进过敏性疾病的最佳临床治疗、教育、研究和培训。





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Translator: Liping Wen MD Peking Medical College Hospital   译者:北京协和医院变态反应科 文利平