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WAO News & Notes - January 2007
Volume 5, Issue 1

Medical Journal Reviews


Medical Journal Reviews
                 
医学杂志回顾

 

Reviewed by Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief and Guest Reviewer Gary Hellermann, PhD

1. Computed tomography (CT)-an increasing source of radiation exposure.
Compared to regular X-rays, CT scans result in much higher cumulative doses of radiation. This review describes various procedures, typical doses, uses and the biological effects of ionizing radiation. No major studies of the health risks from CT scans have been done, but extrapolation from known CT doses to those received in other circumstances suggests caution, especially in light of the very large numbers of people undergoing CT procedures. Editor's comment: Because a CT results in high doses of ionized radiation, other procedures (including an extensive and accurate history and physical), such as MRI or ultrasound, may provide satisfactory diagnostic results when substituted for a CT. Brenner DJ et al., N Eng J Med 2007; 357:2277-2284.
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1. 计算机断层扫描(CT---- 放射线暴露增加的来源
与常规X线检查相比,CT扫描的累计放射暴露剂量要大得多。这篇综述描述了各种放射操作,常用的放射剂量,电离辐射的应用及其生物学效应。目前关于CT带来的健康危害还没有大型的临床研究,但如果用已知的其他环境下相当于CT扫描的暴露剂量对健康的影响来推算,提示我们要小心CT扫描的放射危害,尤其是当考虑到接受CT检查的人群数量庞大时。编者按:由于CT检查导致大剂量的电离辐射,可采用常规检查方法(包括全面细致的病史询问和体格检查),结合使用其他的替代手段,例如核磁共振和超声检查来诊断疾病。Brenner DJ et al., N Eng J Med 2007; 357:2277-2284.

2. Determinants of response to fluticasone propionate (FP) and salmeterol/fluticasone propionate combination (SFC) in the Gaining Optimal Asthma control (GOAL) study.
Asthmatics with uncontrolled disease were given either FP alone or SFC. The GOAL data analysis seeks to determine the factors affecting outcomes and how to better manage asthma. Subjects were categorized into totally controlled (TC), well-controlled (WC) or not well-controlled (NWC) groups. Statistical methods were used to establish the odds ratios for specific factors which reduced the chances for improvement. The primary determinant for the NWC group was smoking, even though all groups improved, especially with SFC. Editor's Comment: The take-home message is clear: tell your asthma patients, if they want to get better, they must stop smoking. Pederson SE et al., J Allergy Clin Immunol 2007; 120:1036-1042.

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2
最佳哮喘控制(GOAL)研究中丙酸氟替卡松(FP)和沙美特罗/丙酸氟替卡松联合治疗(SFC)的疗效决定因素
未控制的支气管哮喘患者分别予以FPSFC治疗。对GOAL数据进行分析,以明确治疗结果的影响因素以及如何优化管理哮喘。根据治疗结果,受试者被分为完全控制组(TC),良好控制组(WC)以及未控制组(NWC)。用统计方法明确各种特定因素降低病情改善率的比值比。吸烟是哮喘控制不良组的首要决定因素。尽管两个治疗组的患者病情均有改善,而SFC组改善更明显。.编者按:本文表明的信息是明确的:告诉你的哮喘患者,如果他们希望病情改善,必须停止吸烟。 Pederson SE et al., J Allergy Clin Immunol 2007; 120:1036-1042.

3. Comparative study of budesonide inhalation suspension (BIS) and monteleukast (M) in young children with mild persistent asthma.
This study compares BIS to M over one year in children 2 to 8 yrs with mild persistent asthma. Subjects (395) in multicenter groups were randomized to receive BIS (0.5 mg) or M (4-5 mg) daily. Outcomes were length of time to first exacerbation and subsequent additional treatment for exacerbation, rates of exacerbation, PEF and QoL assessment. Both BIS and M provided good asthma control, but B was better. Editor's comment: While BIS improves asthma control better than M, the ease of use of the latter sometimes may be advantageous, particularly in young children. Szefler SJ et al., J Allergy Clin Immunol 2007; 120:1043-1050.

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布地奈德吸入粉剂(BIS)和孟鲁司特(M)治疗年幼儿童轻度持续性哮喘的比较
本研究比较了布地奈德吸入粉剂(BIS)和孟鲁司特(M)治疗儿童(28岁)轻度持续性哮喘一年的效果。来自多个研究中心的患者(395)被随机分组,分别接受BIS(每日0.5毫克)或M (每日4-5毫克)治疗。研究终点包括:到首次哮喘加重之间的时间及其额外治疗,哮喘加重的次数,PEF和生活质量评估。两组均提供了良好的哮喘控制,但BIS组更好。编者按:虽然BIS组比M组的哮喘控制率更高,但由于孟鲁司特服用方便,有时可能更有优势,特别是对年幼的哮喘患者。Szefler SJ et al., J Allergy Clin Immunol 2007; 120:1043-1050.

4. Genetic effect of CCR3 and IL5RA gene polymorphisms on eosinophilia in asthmatic patients.
Two factors which affect the eosinophil numbers are the chemokine receptor, CCR3, and the eosinophil survival mediator, IL-5. In this study, single-nucleotide polymorphisms (SNPs) in the genes for CCR3 and IL-5 receptor alpha subunit in a group of 576 Korean asthmatic patients and 180 healthy persons are correlated with asthma susceptibility and eosinophilia. Among the SNPs in the CCR3 gene, all are located in introns and none are associated with asthma susceptibility. However, some asthmatic subjects with CCR3 alterations had lower eosinophil numbers compared to the more common SNPs associated with eosinophilia. IL5RA SNPs resulted in increased eosinophil numbers in asthmatic subjects and when paired with a CCR3 SNP, the effects on eosinophilia were enhanced. Editor's comment: The statistical association of specific SNPs with asthma contributes to the knowledge of asthma pathology. Lee J-H et al., J Allergy Clin Immunol 2007; 120:1110-1117.

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4  CCR3
IL5RA基因多态性对哮喘患者嗜酸粒细胞增多症的遗传学影响
两个因素可影响嗜酸性粒细胞的数目,分别是趋化因子受体( CCR3)和嗜酸粒细胞生存调节因子(白细胞介素5IL-5)。本研究中,对576名韩国哮喘患者和180名健康人的CCR3IL - 5受体α亚基基因的单核苷酸多态性( SNPs )与哮喘易感性及嗜酸粒细胞增多症之间进行了相关性分析。CCR3基因的单核苷酸多态性都位于内含子,且与哮喘易感性之间无相关性。不过,与常见单核苷酸多态性患者相比,有些CCR3基因变异型哮喘患者有较低的嗜酸性粒细胞数目。IL5RASNPs可导致哮喘患者的嗜酸性粒细胞数目增加,当与CCR3SNPs结合起来,可增加 嗜酸粒细胞增多症的可能性。编者按:SNPs与哮喘之间的统计学相关性有助于增加对哮喘病理的了解。Lee J-H et al., J Allergy Clin Immunol 2007; 120:1110-1117

5. Defective T-cell activation caused by impairment of the TNF receptor 2 co-stimulatory pathway in common variable immunodeficiency (CVID).
CVID is characterized by decreased production of B cells and immunoglobulins and an increased susceptibility to bacterial infections. Hereditary defects in T-cell receptor signaling are implicated, but in most cases, the exact abnormality is unknown. This paper examines the TNF-mediated co-stimulatory pathway of T-cell activation in a group of CVID patients compared to healthy controls. The CVID subjects have a normal primary TCR signal (CD69) as well as normal calcium store flux and PKC-theta activation, however, TCR co-stimulation through TNF-RII was severely impaired. Editor's comment: CVID is a complex disorder and understanding genetic defects is important to design new therapies. Aspalter RM et al., J Allergy Clin Immunol 2007; 120:1193-1200.

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5   
普通易变型免疫缺陷( CVID):肿瘤坏死因子受体2TNF-RII)共激活途径障碍导致的T细胞活化障碍
CVID
的特点是B细胞和免疫球蛋白的产生减少,细菌性感染的易感性增加;也可能有T细胞受体信号的遗传缺陷,但在大多数情况下,这种疾病的机制仍不明确。本文比较了CVID患者与健康对照组的肿瘤坏死因子介导的T细胞活化的共激活途径 CVID患者的主要TCR信号( CD69)正常 ,钙内流和蛋白激酶C –θ的活化正常,但TCR通过TNF-RII的共激活途径严重受损。编者按: CVID是一种复杂的疾病,了解其遗传缺陷对设计新疗法非常重要。 Aspalter RM et al., J Allergy Clin Immunol 2007; 120:1193-1200.

6. Genetics of Asthma: Potential implications for reducing asthma disparities.
This review presents what is known about specific gene alterations in minorities and points out areas where there are weaknesses due to small sample size or genetic and environmental heterogeneity. Polymorphisms (SNPs) in the disintegrin and metalloprotease 33 (ADAM33) gene, the IL-4 receptor, the HLA loci and others are discussed in African-American or Hispanic populations compared to whites. Significant differences in the frequency of SNPs and haplotypes are seen. Editor's comment: Elucidation of asthma pathology mechanisms depends on obtaining information on all racial groups. Scirica CV and Celedon JC, Chest 2007; 770S-781S.

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6
哮喘遗传学:减少哮喘异质性的潜在影响
这篇综述介绍了目前关于少数民族特定基因变异的认识,并指出有些研究领域会因样本量小或遗传/环境异质性而产生偏差。本文讨论了白人和非洲裔或西班牙裔人群在解聚素和金属蛋白酶33 ADAM33 )基因,白细胞介素-4受体,人类白细胞抗原(HLA)基因位点的基因多态性( SNPs )。在各组间SNPs频率及单倍型率存在显著性差异。编者按:要阐明哮喘的病理机制,应获取所有种族群体的遗传信息Scirica CV and Celedon JC, Chest 2007; 770S-781S.

7. Diesel-enriched particulate matter (PM) functionally activates human dendritic cells (DC).
Human DC were expanded from peripheral blood by culturing them in the presence of specific cytokines and exposed to PM from cars (gas) or trucks (diesel). The activation phenotype of the DCs was determined by flow cytometry of maturation markers and endocytosis of FITC-dextran. PM from car exhaust had little effect on DC activation, but diesel PM increased secretion of TNF, IL-6 and IFN-gamma and upregulated MHC-II. Both car and diesel exhausts promoted a Th2 cytokine response. Diesel PM specifically stimulates endocytosis by DCs which is different from other activators such as LPS. The enhanced antigen uptake combined with stimulation of maturation marker expression seems to be a unique feature of diesel exhaust and may account for some of its inflammatory effects. Editor's comment: The mechanism of diesel PM effects on DCs remains to be elucidated through additional experiments. Porter M, et al., Am J Resp Cell Mol Biol 2007; 37:706-719.

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柴油颗粒物( PM )激活人体树突状细胞( DC )功能
培养人类外周血树突状细胞,用细胞因子进行扩增,并暴露于从汽车(汽油)或卡车(柴油)颗粒 。用成熟标志和内吞 FITC -葡聚糖的流式细胞仪明确树突状细胞的活化表型。汽车废气对树突状细胞活化影响不大,但柴油颗粒可增加肿瘤坏死因子,白细胞介素-6和干扰素γ的分泌,上调MHC-II。汽车和柴油机尾气均可促进Th2细胞因子反应。柴油颗粒可刺激树突状细胞内吞作用,这是不同于其他激活剂例如内毒素的地方。柴油车尾气可增加树突状细胞的抗原摄取,刺激其成熟标记的表达,这些独特的特点可能导致其炎症效应。编者按:还需要更多的实验以明确柴油颗粒对树突状细胞影响的机制。 Porter M, et al., Am J Resp Cell Mol Biol 2007; 37:706-719.


8. Respiratory effects of exposure to diesel traffic in persons with asthma.

A group of 60 nonsmoking asthmatics with mild to moderate symptoms were recruited and tested during a period free from exacerbations or respiratory infections. They were allowed to continue their regular medications, but not oral corticosteroids. Participants walked for about two hours in one of two areas-a busy street with heavy diesel traffic only or a park away from traffic. Air in each area was sampled and numbers and sizes of PM determined. Spirometry was performed before, during and after the sessions and subjects were asked to record asthma symptoms. Sputum samples were collected for cell counts and analysis of cytokines and ECP. Fractional exhaled NO and breath condensate pH were also measured. Results showed a greater reduction in FEV1 in subjects walking in the city area compared to the park, and moderate asthmatics had a greater drop in FEV1 than mild asthmatics. Other measurements such as decreased pH and increase in sputum myeloperoxidase also Correlated with increased PM. Editor's comment: No difference in symptoms were reported between the city and the park groups, but the extensive physical data implicate diesel PM as pro-inflammatory. McCreanor J et al., N Engl J Med 2007; 357:2348-2358.

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柴油车尾气对哮喘患者呼吸的影响
一组60非吸烟轻中度哮喘患者在无哮喘加重或呼吸道感染期间入组。他们被允许继续规律使用药物,但不能口服皮质激素。受试者在两个区域步行约两小时:一条繁忙的只有重型柴油的车辆的大街或远离交通的公园。两个区域分别抽取空气样本进行尾气中颗粒数量和大小确定。在试验之前,期间和之后进行肺功能测定,并记录哮喘症状。采集痰标本进行细胞计数,并分析细胞因子和ECP 。测定分段呼出气体一氧化氮及呼气冷凝水pH值。结果表明,与公园步行者相比,城市地区步行者的FEV1降低更明显。中度哮喘患者比轻度哮喘患者的FEV1降低更明显。其他指标,例如pH值降低,痰中髓过氧物酶增加,也与柴油车尾气颗粒相关。编者按:尽管城市组和公园组之间在症状报道方面没有任何差别,但很多数据表明柴油车尾气颗粒是一种前炎症物质。 McCreanor J et al., N Engl J Med 2007; 357:2348-2358.

9. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma.
Airway eosinophilia is a prevalent problem in chronic asthma and treatments that reduce IL-5, the cytokine involved in proliferation, survival, migration and maturation of eosinophils (E), seems an ideal target for anti-E therapy. This multicenter, DBPCS of the humanized anti-IL-5 antibody, mepolizumab, seems to argue against this conclusion. Subjects ranged in age from 18 to 55 years and had FEV1s of 50-80 % of predicted. Their asthma control required high doses of ICS (1000 micrograms beclomethasone or equivalent). Doses of mepolizumab, 250 or 750 mg, were given i.v. at monthly intervals and outcomes were measured in terms of FEV1, E counts in serum and sputum, diary cards and QoL questionnaires. There was a significant reduction in the tendency for exacerbation in the group receiving the highest dose of mepolizumab, but otherwise no change in other parameters was observed. Editor's comment: Further investigation into the reasons why anti-IL-5 treatment does not work for asthma may tell us more about its pathogenesis. Flood-Page P et al., Am J Resp Crit Care Med 2007; 176:1062-1071. (editorial by PM O'Byrne, pp. 1059-1060).

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9  Mepolizumab
治疗中度持续性哮喘患者安全性和疗效评估
在慢性哮喘患者,气道嗜酸性粒细胞增多是一个普遍的问题。白细胞介素5可调节嗜酸性粒细胞的扩散,生存,迁移和成熟,因此降低IL-5水平似乎是抗嗜酸粒细胞治疗的理想目标。但这个Mepolizumab(人化抗IL - 5抗体)的多中心双盲安慰剂对照的临床研究似乎得出了相反结论。受试者年龄由1855岁,FEV150-80 %预测值。这些患者需用高剂量吸入皮质激素控制哮喘(1000ug丙酸倍氯米松或等效的其他皮质激素)。Mepolizumab 250750毫克,每月一次静脉注射,疗效指标为FEV1、血和痰嗜酸粒细胞计数、哮喘日记和生活质量问卷。接受最高剂量mepolizumab组中,哮喘加重次数有显著性降低,但其他参数在各组间无明显的差异。编者按:应进一步研究抗IL - 5治疗为什么不适用于哮喘,这也许可以告诉我们更多哮喘发病机制。 Flood-Page P et al., Am J Resp Crit Care Med 2007; 176:1062-1071. (editorial by PM O'Byrne, pp. 1059-1060).


10. Ceramide: A key signaling molecule in a guinea pig model of allergic asthmatic response and airway inflammation.

Ceramide is a membrane-associated sphingolipid that is pro-inflammatory and pro-apoptotic. Using ovalbumin-sensitized guinea pigs, the authors found that lung ceramide production was elevated after allergen challenge. Bronchoconstriction, dyspnea and cough also increased. Pretreatment with an inhibitor of ceramide synthase blocked the allergen-induced inflammatory effects and epithelial cell death. Editor's comment: Pharmacological manipulation of ceramide levels may prove to be a useful therapy for inflammatory lung disease. Masini E et al., J Pharmacol Exp Ther 2007; [Nov. 27, epub ahead of print].

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10 
神经酰胺:过敏性哮喘反应及气道炎症豚鼠模型的一个关键的信号分子  
神经酰胺是一种促炎症和促凋亡的膜相关神经鞘脂类。作者发现,用卵清蛋白致敏豚鼠过敏原激发后,肺中的神经酰胺生产增加, 支气管痉挛、呼吸困难和咳嗽也加重。用神经酰胺合成酶抑制剂预处理可阻断过敏原引起的炎症效果和上皮细胞死亡。编者按:用药物控制神经酰胺的水平可能会称为炎症性肺病的有效治疗手段。 Masini E et al., J Pharmacol Exp Ther 2007; [Nov. 27, epub ahead of print]

11. Medical progress: sarcoidosis.
First described in 1899, sarcoidosis is characterized by the formation and accumulation of benign granulomas containing activated T-cells and macrophages secreting cytokines and chemokines. The clinical characteristics, different organ involvement, the differential diagnosis, sarcoidosis in children and treatment are reviewed. Editor's comment: Great review of a disease whose etiology remains elusive. Iannuzzi MC et al., N Engl J Med 2007; 357:2153-2165.

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 11 
医疗进展:结节病
结节病于1899年被首次发现。其特点是良性肉芽肿形成,其中含有活化T淋巴细胞和可分泌细胞因子和趋化因子的巨噬细胞。本文综述了结节病的临床特点、不同的器官受累、鉴别诊断、儿童结节病和结节病的治疗。编者按:这是对这一病因并不明确的疾病的非常好的综述。Iannuzzi MC et al., N Engl J Med 2007; 357:2153-2165

 

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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