WAO News and Notes - Medical Reviews
Volume 5, Issue 7 Reviews - July 2008
Medical Journal Reviews

Dr. Mark Glaum, WAO Guest Editor reviewed premier medical journal articles for practicing allergists. Read his top 3 picks below and for the other 7 reviews, click here.

To read translations of past Medical Journal Reviews, click here.

1. ASTHMA EXACERBATIONS DURING PREGNANCY INCREASE RISK OF CONGENITAL MALFORMATIONS
Asthma exacerbations are not unusual events during pregnancy. A Canadian cohort of 4344 pregnancies of asthmatic women was examined for evidence of asthma exacerbations during the first trimester. Incidence of congenital malformation at birth and at one year of life was compared in women who experienced asthma exacerbation vs. those who did not. The prevalence of malformations was 12.8% in women who had an exacerbation vs. 8.9% in women who did not. Editor's comment: Aggressive management of asthma and its comorbidities is important in pregnancy as maternal exacerbations appear to increase the risk of congenital malformations. Blais L, Forget A. J Allergy Clin Immunol 2008;121: 1379-84

妊娠期哮喘恶化增加胎儿先天畸形的危险

妊娠期间哮喘恶化并不少见。研究者调查了加拿大名哮喘孕妇在其早孕期有无发生哮喘恶化。比较经历了哮喘恶化及未经历哮喘恶化的孕妇其胎儿在出生时及生后年先天畸形的发病率。有过一次哮喘恶化的妇女所生的孩子先天畸的患病率为12.8%,而没有哮喘恶化的妇女的孩子只有8.9%的患病率。编者点评:妊娠期强化控制哮喘及其并发症非常重要,因为母亲哮喘恶化会增加婴儿患先天畸形的危险。Blais L, Forget A. J Allergy Clin Immunol2008;121: 1379-84

2. DUST MITE ALLERGEN DIRECTLY STIMULATES DENDRITIC CELLS TO PRIME TOWARD TH2 AND TH17 RESPONSES
Interleukin 6 plays in important role in regulating T helper cell differentiation into Th1, Th2 and Th17 subsets. These investigators studied pathways in dendritic cells that promote IL-6 production. Incubation of murine dendritic cells with either dust mite allergen or cholera toxin directly resulted in increased surface expression c-Kit and its ligand, stem cell factor (SCF). As a result of this expression, IL-6 production was also enhanced. Interruption of dendritic cell c-Kit and IL-6 signaling abrogated Th2 and Th17 lymphocyte responses in airways of allergen-sensitized and challenged mice. Editor's comment: Multiple antigens, including dust mite allergen, directly target dendritic cells through c-Kit and IL-6 expression to promote allergic inflammation. Krishnamoorthy N, Oriss TB, Paglia M, et al. Nat Med 2008; 14: 565-73

尘螨变应原直接刺激树突细胞使之诱导TH2TH17细胞应答

白介素6在调节T辅助细胞分化为Th1,Th2,以及Th17亚群上有重要作用。作者研究了树突细胞促Il-6产生的途径。将鼠类树突细胞与尘螨变应原或霍乱毒素共同孵育,可直接导致树突细胞表面ckit<及其配体-干细胞因子(SCF)的表达增加,随之增加Il-6的生成。干扰树突细胞cKit以及Il-6信号途径阻断了已被变应原致敏并被激发的大鼠气道中Th2及Th17淋巴细胞的应答。编者点评:多种抗原,包括尘螨变应原,可通过直接增加树突细胞ckitIl-6的表达来推动过敏的炎症进程。Krishnamoorthy N, Oriss TB, Paglia M, et al. Nat Med 2008; 14: 565-73

3. GRASS POLLEN IMMUNOTHERAPY INDUCES EARLY IL-10 PRODUCTION PRIOR TO EXPRESSION OF IgG4
The aim of this study was to examine the relationship between clinical responsiveness to grass pollen immunotherapy (GIT), regulatory cytokine production and antibody responses to allergen. 18 subjects with severe seasonal allergic rhinitis were randomized to receive injections of grass allergen vaccine or placebo over one year. Subjects' sera were assayed for IL-10, IL-5, IFN-g, allergen-specific IgG4, IgE and IgA. Repeated testing of early and late phase skin responses to intradermal grass allergen was performed. Significant induction of IL-10 and a reduction in late phase skin reactions was observed after only four weeks in the GIT group as compared to placebo. Editor's comment: Grass pollen immunotherapy is associated with early expression of inhibitory cytokines and inhibition of late phase responses. Francis JN, James LK, Paraskevopoulos G, et al. J Allergy Clin Immunol 2008; 121: 1120-5

牧草花粉免疫治疗诱导在IgG4表达之前Il-10的产生

本研究旨在探索牧草花粉免疫治疗的临床应答与调节性细胞因子的产生以及变应原抗体应答的关系。18名有严重季节性过敏性鼻炎的患者随机接受一年牧草花粉变应原疫苗或安慰剂的注射。检测患者血清IL-10, IL-5, IFN-g,变应原特异IgG4,IgE以及IgA的水平。多次测定针对皮内牧草变应原的早期相及迟发相皮肤应答。 经过4周免疫治疗,与安慰剂组比较,治疗组Il-10的产生显著增加,而皮肤迟发相反应明显降低。编者点评:牧草花粉免疫治疗引起抑制性因子的早期表达,并抑制迟发相反应。Francis JN, James LK, Paraskevopoulos G, et al. J Allergy Clin Immunol 2008; 121: 1120-5

4. PRESENCE OF RHINOVIRUS IN LOWER AIRWAYS OF ASTHMATICS
Human rhinovirus (HRV) is a common cause of asthma exacerbations. The aim of this study is to determine if patients with stable asthma are more likely to harbor HRV in their bronchi than non-asthmatic controls. HRV was detected in endobronchial biopsies by in situ RT-PCR from 73% of stable asthmatics as compared to 22% of non-asthmatic controls (p<0.001). Asthmatics positive for HRV also demonstrated decreased FEV1, and increased numbers of eosinophils in peripheral blood and bronchial tissue. Editor's comment: Rhinovirus may become a chronic lower airway infection and contribute to the persistence and severity of asthma. Wos M, Sanak M, Soja J, et al. Am J Respir Crit Care Med 2008; 177:1082-9

哮喘患者下呼吸道内的鼻病毒

人鼻病毒(HRV)是哮喘恶化的常见原因。本研究旨在明确与无哮喘的健康对照相比,稳定哮喘的患者气道内更易出现HRV的定植。通过原位RT-PCR法在73%哮喘稳定期患者的气管内活检组织中发现了HRV,而在无哮喘的健康对照中只有22%<检测到HRV。HRV阳性的哮喘患者FEV1低且外周血及气管组织中嗜酸细胞增高。编者点评:鼻病毒可造成慢性下呼吸道感染,与哮喘的持续性及严重性相关。Wos M, Sanak M, Soja J, et al. Am J Respir Crit Care Med 2008; 177:1082-9

5. POLYMORPHISMS IN FcεR1 ARE ASSOCIATED WITH ASPIRIN-SENSITIVE URTICARIA AND ATOPY
Chronic urticaria (CU) is a common, bothersome condition that affects a significant portion of the general population. In a Korean cohort, over 35% of CU patients were aspirin-sensitive following blinded oral provocation. Four polymorphisms of the beta and gamma subunits of the FcεR1 were analyzed by genotype and haplotype in 119 aspirin-sensitive CU subjects, 154 aspirin-tolerant CU subjects and 224 healthy controls. Two polymorphisms (one in the beta and one in the gamma subunit) were associated with a higher frequency of atopy (positive skin-prick testing to one or more common aeroallergens) in the aspirin-sensitive CU subjects (p = 0.02 and p = 0.04 respectively) but not in other CU subjects or controls. Editor's comment: Polymorphisms in the FcεR1 receptor may predispose toward certain phenotypes of urticaria and atopy. Palikhe N, Kim S, Yang E, et al. Allergy Asthma Proc 2008; 29: 250-7

FcεR1多态性与阿司匹林敏感性的荨麻疹及特应性相关

慢性荨麻疹(CU)影响很多人,是一个很让人烦恼的常见病。在一项韩国的队列研究中,35%以上的荨麻疹患者在盲法口服激发试验中表现为阿司匹林敏感。 对119名阿司匹林敏感的慢性荨麻疹患者、154名阿司匹林耐受的慢性荨麻疹患者以及224名健康对照者的FcεR1 的beta及gammma亚基的四个多态性位点进行了基因型及单体型分析。在阿司匹林敏感的慢性荨麻疹患者,有两个多态性(一个在beta亚基,一个在gamma亚基)与高发的特应性(对一个或多个常见气传变应原皮肤点刺阳性)相关,但其它慢性荨麻疹患者或正常对照组没有这种相关关系。编者点评:FcεR1受体多态性可能与荨麻疹及特应性的某种表型相关。 Palikhe N, Kim S, Yang E, et al. Allergy Asthma Proc2008; 29: 250-7

6. IDENTIFICATION OF FIVE MAJOR QUANTITATIVE ASTHMA PHENOTYPE FACTORS
Asthma is a heterogeneous disease caused by a complex interaction between genetic and environmental factors. These investigators sought to determine the minimum number of features needed to characterize subjects with asthma focusing on important environmental and genetic contributors. Subjects aged 7-35 years with physician-diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families in the Genetics of Asthma International Network. Five distinct factors identified were baseline pulmonary function, specific allergen sensitization by skin testing, self-reported allergies, symptoms characteristic of rhinitis and symptoms characteristic of asthma. These factors correlated with serum IgE, methacholine PC20 and nocturnal asthma symptoms. Editor's comment: Efforts continue to better define asthma phenotypes. Pillai SD, Tang Y, van den Oord E, et al. Clin Exper Allergy 2008; 38: 421-9

发现了五个主要的有定量作用的哮喘表型因子

哮喘是由遗传及环境因素共同作用导致的异质性疾病。研究者要寻找用最少的特征来描述哮喘患者的特点,尤其是重要的遗传及环境致病因素。对来自哮喘遗传学国际网中1022个核心家庭的年龄在7-35岁,由医生诊断为哮喘的患者及其有症状的同胞兄弟进行调研。发现了五个显著因素:基线肺功能,皮肤测试有变应原致敏,主诉过敏,鼻炎的典型症状及哮喘的特殊症状。这些因素与血清IgE,乙酰甲基胆碱PC20以及哮喘的夜间症状相关。编者点评:不断有研究致力于对哮喘表型做出更好的描述。Pillai SD, Tang Y, van den Oord E, et al. Clin Exper Allergy 2008; 38: 421-9

7. MUCOSAL IMMUNE RESPONSE TO LARYNGOPHARYNGEAL REFLUX
Laryngopharyngeal reflux (LPR) is a common problem affecting up to 20% of the general population and is a common cause of chronic cough. This study examines the mucosal immune response to LPR. 12 subjects with previously diagnosed LPR and 11 control subjects underwent laryngeal biopsy. Specimens were examined by quantitative multi-color immunofluorescence microscopy for expression of cell-specific markers for lymphocytes, granulocytes, monocytes, classical and non-classical MHC molecules. An increase in percentage of mucosal area CD8+ lymphocytes but not other cell types was observed in LPR subjects (p<0.005). There was also colocalization of natural killer T cells (NKT) with CD1d in LPR subjects (p<0.01). Editor's comment: The nonclassical MHC molecule CD1d may be involved in the immune response associated with LPR suggesting new potential targets for diagnosis and treatment of this condition. Rees LEN, Laszlo P, Gutowska-Owsiak D, et al. Am J Respir Crit Care Med 2008; 177: 1187-93

喉咽返流的粘膜免疫应答

喉咽返流(LPR)是常见病,见于20%的普通人群,是慢性咳嗽的常见原因。本文研究了LPR的粘膜免疫应答。既往诊断LPR的12名患者及11名对照者接受了喉组织活检。活检标本用定量多色免疫荧光显微镜检测细胞表面淋巴细胞,粒细胞,单核细胞的特异性标记以及经典或非经典MHC分子。LPR患者的喉粘膜中CD8+淋巴细胞比率增加,而其它细胞没有增多。LPR患者还有表达CD1d的自然杀伤T细胞(NKT)的定植。编者点评:非经典MHC分子CD1d可能与LPR的免疫应答相关,这为诊断及治疗该病提供了新的指标。Rees LEN, Laszlo P, Gutowska-Owsiak D, et al. Am J Respir Crit Care Med 2008; 177: 1187-93

8. TREATMENT OF OBSTRUCTIVE SLEEP APNEA REDUCES ELEVATIONS IN SERUM SOLUBLE TUMOR NECROSIS FACTOR-a RECEPTOR-1 (sTNFR-1)
Inflammation may play an important role in the development of cardiovascular complications from obstructive sleep apnea (OSA). The purpose of this study is to examine levels of serum and urinary inflammatory markers, and associate any effect of nasal continuous positive airway pressure (CPAP) on these markers in patients with OSA. 30 subjects with newly diagnosed OSA (AHI 43.8±27.0 h-1) and 15 healthy obese subjects were randomized to receive continuous positive airway pressure (CPAP) or sham CPAP for three months. Urinary levels of norepinephrine and epinephrine as well as plasma soluble tumor necrosis factor-a receptor-1 (sTNFR-1), TNF, IL-6 and leukotriene-B4 (LTB4) levels were obtained at baseline and at three months. Nocturnal urinary levels of norepinephrine, epinephrine, and sTNFR-1 (1053±269 vs. 820±166, pg/ml-1, p=0.032) were higher in OSA patients at baseline, however after three months of effective CPAP usage, only sTNFR-1 levels were significantly reduced (1053±269 vs. 899±254, pg/ml-1, p<0.05). Editor's comment: CPAP reduces one marker of inflammation in OSA. Arias MA, Garcia-Rio A, Alonso-Fernandez A, et al. Eur Respir J 2008; doi:10.1183/09031936.00007008

治疗阻塞性呼吸暂停降低血清可溶性肿瘤坏死因子a受体1 (sTNFR-1)

炎症在阻塞性睡眠暂停(OSA)导致的心血管并发症的发生中起到了重要作用。本研究目的在于检测血清及尿中炎症因子的水平,评价鼻持续气道正压通气(CPAP)对于OSA患者体内炎症因子的影响。30名新诊断OSA的患者及15名健康的肥胖者随机接受三个月的持续气道正压通气(CPAP)或虚拟CPAP治疗。测定尿中去甲肾上腺素、肾上腺素以及血浆可溶性肿瘤坏死因子a受体1 (sTNFR-1),TNF, IL-6 及白三烯-B4 (LTB4)在基线期及治疗3个月的水平。基线状态下OSA患者的夜尿去甲肾上腺素、肾上腺素以及sTNFR-1水平均较高 (1053269 vs. 820166, pg/ml-1, p=0.032) ,而经过三个月有效的CPAP治疗后,只有sTNFR-1显著降低(1053269 vs. 899254, pg/ml-1, p<0.05)。编者点评:CPAP可以降低OSA的一个炎症指标。Arias MA, Garcia-Rio A, Alonso-Fernandez A, et al. Eur Respir J 2008; doi:10.1183/09031936.00007008

9. REVIEW OF ASTHMA PATHOGENESIS
This concise review of asthma pathogenesis provides an overview of the inflammatory airway immune response in asthma and discusses individual immunoreactive cell types involved in this process. Concepts of airway remodeling are covered and new approaches for categorizing asthma phenotypes are introduced. Editor's comment: Asthma is a complex "Syndrome of Syndromes." Holgate S. Clin Exp Allergy 2008: 38:872-97

哮喘病理机制的综述

这篇综述对哮喘病理进行了详细回顾,综述了气道对炎症的免疫应答,论述了哮喘致病机理中的免疫活性细胞。文章涉及气道重塑的概念,介绍了哮喘表型分类的新方法。编者点评:哮喘是一个复杂的综合症的综合征Holgate S. Clin Exp Allergy 2008: 38:872-97

10. EOSINOPHILS IN ALLERGY AND RELATED DISEASES
This entire issue of International Archives of Allergy and Immunology summarizes the work presented at the 19th annual workshop on Eosinophils in Allergy and Related Diseases held in Tokyo on June 30, 2007. Included in the Proceedings are 15 original papers and one review. Editor's comment: An excellent update on eosinophil biology. Makino S, Ishikawa T, Takeshi F, et al. Int Arch Allergy Immunol 2008: 146 (suppl 1):1-92

过敏及相关疾病中的嗜酸细胞

这一期的过敏及临床免疫学国际期刊总结了年月30日在东京举行的第19届年度研讨会上发表的关于嗜酸细胞在过敏以及相关疾病中的作用的研究。该期刊包括了15篇论著及一篇综述。编者点评:这是有关嗜酸细胞生物学的非常好的最新综述。Makino S, Ishikawa T, Takeshi F, et al. Int Arch Allergy Immunol 2008: 146 (suppl 1):1-92

Translated by Manli Qing, PUMCH, China

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