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WAO News & Notes - November 2007
Volume 4, Issue 11

Medical Journal Reviews
医学期刊回顾   200711月(第11期)

Medical Journal Reviews


Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chiefand Guest Reviewer Gary Hellermann, PhD, reviewed premier medical journal articles for practicing allergists.


Richard F. Lockey教授, 医学博士, WAO网站主编;Gary Hellermann,博士,客座评论家, 为从业变态反应科医生回顾了主要医学期刊的一些重要文章。


1. Nothing to cough.

This is a case report article of a 73-year-old male with a 4-day history of a nonproductive cough that worsened at night. The differential cough is extensive and allergists/immunologists regularly see individuals who have a chronic cough of unknown etiology. In this particular case report, the cough is not secondary to upper respiratory tract infections, upper airway cough syndrome (post nasal drip), gastroesophageal reflux disease, asthma, cigarette smoking or the use of ACE inhibitors. It is caused by B. pertussis, a resurgent problem associated with the transmission of this organism in the face of waning vaccine-induced immunity among adults and adolescents. Erythromycin or another macrolide usually eliminates the organism within five days; without treatment the patient remains contagious for one month or more and the cough lasts for weeks. Childhood vaccination for B. pertussis wanes after five to ten years, accounting for the resurgence of this disease. Editor's Comment: Pertussis can account for up to 32% of cases of prolonged cough in adolescents and adults. Re-immunization with tetanus, diphtheria and pertussis (Tdap) vaccine is now recommended for adults 19 to 64 by the U.S. Communicable Disease Center. Cornia B et al. N Engl J Med 2007; 357:1432-1437.



这是一个病例报告。一位73岁的男性患者,临床表现为无痰性干咳4天,夜间症状加重。普通内科医生和变态反应科医生对这种原因不明的慢性咳嗽进行鉴别诊断的涉及范围非常广泛。该患者的咳嗽既不是继发于上呼吸道感染,也不是上气道咳嗽综合征(鼻后滴液)和胃食管反流病,也不是哮喘,吸烟或使用血管紧张素转换酶抑制剂造成的咳嗽,而是由百日咳杆菌感染所致。在成年人和青少年疫苗注射后免疫反应逐渐减弱的情况下可能发生,是一个死灰复燃的问题。红霉素或其他大环内酯类通常可于5天内杀灭细菌,但未经治疗的患者在为期1个月或以上的时间内具有传染性,咳嗽可持续数周。儿童预防接种百日咳5~10年后免疫力减弱,可使此病死灰复燃。编者按:在青少年和成年慢性咳嗽患者中,高达32%由百日咳造成。目前美国传染病中心建议美国19-64岁的成年人再次接种破伤风-白喉-百日咳(Tdap)疫苗。Cornia B et al. N Engl J Med 2007; 357:1432-4327.


2. Allergic airway responses in obese mice.

A link between asthma and obesity has been demonstrated in epidemiological reports, but me- chanistic studies are few. Here, an obese mouse (ob/ob) model is used to examine the effects of obesity on ovalbumin (OVA)-induced asthma. Pulmonary resistance is higher in ob/ob mice than wild type (WT) as is also the IgE level. There is no difference in the Th2 cytokine level and lung cell infiltration is actually lower in ob/ob mice compared to WT. Editor's Comment: The significant increase in airway hyperreactivity without concomitant increase in Th2 cytokines or cellular infiltration suggests additional mechanisms in obesity-associated asthma. Johnston RA et al. Am J Resp Crit Care Med 2007; 176: 650-658.



哮喘和肥胖之间的相关性已被流行病学报道证明,但机制研究却很少。本研究用肥胖鼠模型(ob/ob)研究肥胖对卵清蛋白OVA)诱发哮喘小鼠的影响。在ob/ob小鼠,肺阻力和IgE水平均比野生型(WT)高。ob/ob小鼠和野生型小鼠相比,Th2细胞因子水平不存在差异,而肺炎症细胞浸润水平较低。编者按:在气道反应性增高同时没有伴随增加Th2细胞因子或细胞浸润的增加,意味着肥胖相关性哮喘可能有其他发病机制。Johnston RA et al. Am J Resp Crit Care Med 2007; 176: 650-658.


3. Effectiveness of influenza vaccine in the community-dwelling elderly.

This study of 713,872 person-season observations of pooled data from 18 cohorts of community- dwelling elderly members of various health maintenance organizations in the United States deter- mined that during 10 seasons, influenza vaccine was associated with significant reductions in the risk for hospitalization for pneumonia or influenza and the risk of death among community-dwelling elderly persons. Vaccination was associated with 27% reduction in the hospitalization risk for pneumonia or influenza (OR, 0.73; 95% CI, 0.06 to 0.77) and a 48% reduction in risk of death (OR, 0.52; 95% CI, 0.50 to 00.55). Editor's comment: Influenza vaccine is indicated for high risks subjects. Nichol K et al, N Engl J Med 2007; 357:1373-81. Treanor JD, editorial, 357:1439-1441.



这项研究观察10年来美国不同健康维护组织对社区居住老人进行的18个组群研究中样本池中的713 872人一季的观察,明确了流感疫苗应用可显著减少社区居住老人因肺炎或流感住院的风险和死亡的危险。接种疫苗后因肺炎或流感住院的风险减低27%OR, 0.73; 95% CI, 0.06 to 0.77),死亡的风险降低48%OR, 0.52; 95% CI, 0.50 to 00.55)。编者按:在高危人群,应注射流感疫苗。Nichol K et al. N Engl J Med 2007; 357:1373-81. Treanor JD, editorial, 357:1439-1441.


4. Clinical improvement and immunological changes in atopic dermatitis patients undergoing subcu- taneous immunotherapy with a house dust mite allergoid: a pilot study.

Subcutaneous allergen-specific immunotherapy (SCIT) is effective in treating allergy and this study aims to determine if SCIT will benefit atopic dermatitis (AD) patients sensitive to house dust mite (HDM) allergens. 25 subjects, who had been diagnosed with AD for over two years, and had FEV1>70% and positive skin-prick test to Der p and/or Der f were enrolled. SCIT injections of HDM allergoid were given weekly for the first four weeks, then every four weeks up to 32 weeks. AD symptoms were quantified using the standardized SCORAD (scoring of atopic dermatitis) system. SCIT with HDM caused a significant reduction in objective and subjective SCORAD as well as reduction in HDM-specific IgE; the greatest improvement in eczema being seen in those with the severest disease. Editor's Comment: This small pilot study offers significant hope that allergen- specific SCIT may be helpful for AD. Bussmann C et al. Clin Expt Allergy 2007; 37:1277-1285.



皮下注射过敏原特异性免疫治疗(SCIT 可有效治疗尘螨过敏,本研究旨在确定该疗法是否对尘螨过敏的特应性皮炎患者有效。25例已被诊断特异性皮炎两年以上的患者,FEV1>70%,粉尘螨或户尘螨皮肤点刺试验阳性者入组。尘螨皮下注射免疫治疗前四周每周一次,以后每4周注射一次共计32周。用标准化SCORAD量表对AD患者症状进行定量评估。用尘螨过敏原进行皮下免疫治疗可显着降低,客观和主观SCORAD评分,同时可降低尘螨特异性IgE水平,在症状最重的患者,湿疹的改善最明显。编者按:这一小样本的研究成效提示尘螨特异性免疫治疗特异性皮炎大有希望。Bussmann C et al. Clin Expt Allergy 2007; 37: 1277-1285.


5. Mast cell (MC)-derived interleukin-10 (IL10) limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B.

The immune system possesses a natural anti-inflammatory activity that limits leukocyte infiltration and tissue damage. IL10 is a cytokine produced by macrophages, B cells, T helper type 2 cells, regulatory T cells and, as reported here, mast cells. Mice deficient in MC production were examined for inflammation in response to the urushiol (sensitizer) or chronic UVB irradiation. They that showed increased contact hypersensitivity (CHS) was reversed by injecting them with wild type MCs. MCs appear to be a major source of IL10 and exert an anti-inflammatory and immunosuppressive effect on CHS and the effects of chronic UVB irradiation. Editor's Comment: This finding in mice of a role for MCs in limiting CHS inflammation may be important for human CHS. Grimbaldeston MA et al. Nat Immunol 2007; 8:1095-1104.



免疫系统具有天然的抗炎活性,可限制白细胞浸润和组织损伤。 IL-10这种细胞因子产生于巨噬细胞,B细胞,TH2型细胞,调节性T细胞和本文研究的肥大细胞。观察肥大细胞缺陷的小鼠以漆酚(增敏剂)或长期紫外线的照射后的炎症反应。研究表明这些小鼠接触过敏反应性增高(CHS),予以野生型肥大细胞注射后这种高反应性被逆转。肥大细胞似乎是IL-10的主要来源,对CHS和慢性紫外线的照射有抗炎和免疫抑制效应。编者按:肥大细胞可限制小鼠体内的CHS炎症,这一发现对人类CHS可能也有重要意义。Grimbaldeston MA et al. Nat Immunol 2007; 8:1095-1104.


6. Allergic rhinitis (AR) and onset of bronchial hyperresponsiveness (BHR).

There is an association between AR and increased BHR, but studies have not definitively linked AR to the onset of BHR. Data from the European Community Respiratory Health Survey (ECRHS) was used in this report to examine the factors associated with developing BHR (defined as a 20% decrease in FEV1 in response to 1 mg methacholine). A cohort of 3719 subjects without BHR at baseline and, with or without, AR or atopy was examined at follow-up (about nine yrs later). The incidence of BHR is 9.7% in subjects with AR, 7.0% in subjects with atopy but not AR, and 5.0% in subjects with neither. When the AR is treated with ICS, the remission of BHR is enhanced. Editor's Comment: AR seems to be a risk factor for onset of BHR, but the exact mechanism is unknown. Shaaban R et al. Am J Resp Crit Care Med 2007; 176: 659-666.



过敏性鼻炎和气道高反应性具有相关性,但关于过敏性鼻炎和气道高反应性发生的关联并没有明确研究。这份报告的数据来自欧洲社区呼吸健康调查(ECRJS),研究气道反应性增高的相关因素(BHR定义为吸入1毫克甲胆碱后FEV1下降20%)。这是一个3719例患者的队列研究,基线期无气道高反应性,伴或不伴过敏性鼻炎/过敏体质,进行随访调查(约9年以后)。在伴过敏性鼻炎的患者气道高反应的发生率为9.7% ,有过敏体质但没有过敏性鼻炎的个体中,7.0%发展为气道高反应,不伴上述因素的个体中,5.0%发展为气道高反应。如用吸入皮质激素治疗过敏性鼻炎,可降低气道高反应的发生率。编者按:过敏性鼻炎似乎是气道高反应性发病的一个危险因素,但确切机制尚不清楚。Shaaban R et al. Am J Resp Crit Care Med 2007; 176: 659-666.


7. Phagocyte-derived catecholamines enhance acute inflammatory injury.

There is a large body of evidence that the inflammatory response is intimately linked to autonomic signals through specific receptors on immune system cells. In this paper, not only do immune cells respond to neurohormones but they also produce them. Rat alveolar macrophages incubated with bacterial lipopolysaccharde produce high levels of adrenalin and noradrenalin and express the enzymes necessary for producing and degrading catecholamines. The secretion of macrophage catecholamine promotes lung inflammation and antagonist blockade of adrenoceptors prevents this. Similar experiments with neutrophils from peripheral blood (including human) show that these cells also produce inflammatory catecholamines. Editor's Comment: The multi-layered complexity of the immune response is further demonstrated by this finding of neurohormone production by phagocytic cells. Flierl MA et al. Nature 2007; 449:721-725.



大量的证据表明,炎症反应与免疫细胞上的特定受体和自主信号系统密切相关。在本文中,免疫细胞不仅对神经激素产生反应,同时还可产生这些神经激素。大鼠肺泡巨噬细胞用细菌脂多糖培养后,产生高水平的肾上腺素和去甲肾上腺素,并表达生产和降解儿茶酚胺所必需的酶。吞噬细胞可分泌心儿茶酚胺的促进肺部炎症,用拮抗剂阻断肾上腺素受体可阻断这一反应。用外周血中性粒细胞(包括人类外周血中性粒细胞)进行类似实验显示,这些细胞也产生炎症性儿茶酚胺。编者按:吞噬细胞可产生神经激素,这一发现进一步证明了免疫反应的多层次性和复杂性。Flierl MA et al. Nature 2007; 449: 721-725.


8. Inhibition of allergen-induced airway remodeling by tiotropium and budesonide: a comparison.

The neurotransmitter, acetylcholine, acts on muscarinic receptors to cause airway smooth muscle contraction, but chronic signaling can also lead to production of pro-inflammatory mediators and mitogenic proteins. This study looked at the effects of the anticholinergic, tiotropium bromide, in comparison with budesonide on airway remodeling, contractility and mucus production in ovalbumin- allergic guinea pigs. Both compounds were similarly effective in reducing tracheal hypercontractility and mucus cell hyperplasia. Editor's Comment: This report demonstrates that acetylcholine acting through muscarinic receptors may play an important role in the pathophysiology of airway remodeling. Bos IST et al. Eur Resp J 2007; 30:653-661.



神经递质乙酰胆碱作用于毒蕈碱受体引起气道平滑肌收缩,但长期信号传导作用也能导致生成前炎症介质和丝蛋白。这项研究的目的是观察卵清蛋白致敏豚鼠用抗胆碱能药物--溴化异丙托品对气道重塑,支气管收缩性和黏液分泌的效果,并将其与布地奈德作对比。这两种化合物同样有效地降低气道高反应性和粘液细胞增生。编者按:本研究表明:在气道重塑病理生理学中,乙酰胆碱通过毒蕈碱受体可能起着重要的作用。Bos IST et al. Eur Resp J 2007; 30: 653-661.


9. Anti-inflammatory activity of human IgG4 antibodies by dynamic FAb arm exchange.

IgG4 subtype antibodies differ from other IgGs in having anti-inflammatory activity, and this property has made them useful in immunotherapy. There have been reports that one monospecific IgG4 can switch a heavy/light chain with a different IgG4 to generate a bi-specific molecule. In this study, IgG4 in blood samples from subjects sensitive to cat and birch allergens was found to react with both antigens. Antibody arm exchange was also seen in mice injected with cat-specific and birch-specific IgG4s. Breakage of disulfide bonds between the arms by in vitro reaction with the reducing agent glutathione verified that this mechanism was involved in the exchange. Using a rhesus monkey model of immune myasthenia gravis, injection of IgG4 specific for the acetylcholine receptor (AChR) neutralized the pathological effects of AChR-specific IgG1. Editor's Comment: This unusual anti-inflammatory property of IgG4 antibodies may prove to be a promising avenue for developing more effective immunotherapy strategies. Kolfschoten M et al. Science 2007; 317: 1554-1557.



IgG4抗体不同于其他IgG 之处在于具有抗炎活性,而这一特性使得它们在免疫治疗中发挥重要作用。有研究发现,一种单一特异性的人IgG4可以通过和另一种特异性IgG4交换重/轻链,从而产生双重特异性的IgG4。在这项研究中,猫和桦树过敏的病人血液样本中IgG4既对猫过敏原有反应,又对桦树过敏原有反应。用猫特异性IgG4和桦木特异性IgG4给小鼠注射后,也发现了这种抗体的臂交换现象。用还原剂谷胱甘肽通过体外反应的方法打破抗体臂之间的二硫键,表明这个机制参与了抗体臂的交换。给免疫性重症肌无力恒河猴模型注射人乙酰胆碱能受体(AChR)IgG4抗体,可中和AchR特异性 IgG1造成的病理改变。编者按:这种具有不寻常的免疫学特性的特异性IgG4抗体也许能为发展更有效的免疫治疗策略提供一条前景光明的途径。Kolfschoten M et al. Science 2007; 317:1554-1557.


10. A critical appraisal of "chronic Lyme disease".

Lyme disease, the most common tick borne infection in the Northern hemisphere, is caused exclusively by Borrelia burgdorferi, whereas in Europe it is caused by B. afzelii, B. garinii, B. burgdorferi and other species of Borrelia. This article is a very extensive and critical review of the subject of "chronic Lyme disease". The authors indicate that this disease is the latest in a series of syndromes postulated to attribute medically unexplained symptoms to particular infections. Earlier examples include "chronic candida syndrome" and "chronic Epstein-Barr virus". They go on to state that "chronic Lyme disease", which is equated to chronic B. burgdorferi, is a misnomer, and prolonged treatment with potentially dangerous and expensive antibodies is not warranted. Editor's comment: This is an excellent article for all to read about a "disease" for which there is no good scientific evidence. Feder H et al. N Engl J Med 2007; 357:1422-1430.



莱姆病是在北半球最常见的蜱传播感染疾病,唯一的病原体是伯氏疏螺旋体Borrelia burgdorferi而在欧洲,这种疾病可由B. afzelii, B. garinii, Borrelia burgdorferi和其他种包柔氏螺旋体引起。本文是一篇关于“慢性莱姆病”的全面评论性的综述。作者认为,这种疾病被用来描述一些假定由感染引起的医学上无法解释的一系列症状。先前的例子包括“慢性念珠菌综合征”和“慢性爱泼斯坦-巴尔病毒”(EB)。他们指出,“慢性莱姆病”意思等同于慢性伯氏疏螺旋体感染,这是名不副实的,而使用具有潜在危险且价格昂贵的抗体进行长期治疗是没有正当理由的。编者按:这是一篇关于没有科学证据的“病”的非常好的文章。Feder H et al. N Engl J Med 2007; 357:1422-1430.



译者:北京协和医院 文利平   

WAO Web Site Editors:
Editor-in-Chief: Richard F. Lockey, USA
Regional Assistant Editors: Juan Carlos Ivancevich, Argentina; Nikolaos G. Papadopoulos, Greece; Hirohisa Saito, Japan; Cassim Motala, South Africa; Emil J. Bardana, Jr., USA
Editors at Large: Connie H. Katelaris, Australia; Bob Q. Lanier, USA; Cassim Motala, South Africa; Ruby Pawankar, Japan
Translators: Juan Carlos Ivancevich (Spanish), Dirceu Sole, Carlos Nunes (Portuguese), Yehia El Gamal (Arabic), Hirohisa Saito (Japanese), Yin Jia, Gu Jian Qing, Wen Li Ping, Guan Kai (Chinese), Krysztof Kowal (Polish), Georgy Gudima (Russian)

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The World Allergy Organization (WAO) Web Site supports the WAO mission. WAO is a global resource and advocate in the field of allergy, asthma and clinical immunology, advancing excellence in clinical care, education, research and training through a world-wide alliance of allergy and clinical immunology societies. 

The WAO website is an up-to-date compendium of information about allergy, asthma and immunology for all physicians, including specialists, other health care professionals and patients.  It also provides a network for global contacts in the field. 

The following information is found on the WAO website:

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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。





1. 每月一次更新的WAO新闻和纪要,被翻译成七种语言,从大约15本主要专业杂志中摘取的文献摘要,公布会议教育资源、新书评论

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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