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December Medical Journal Review
十二月医学杂志回顾
WAO Now: What's New in the World of WAO
今日WAO:WAO领域新进展
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December World Medical Journal Review 十二月医学杂志回顾

Shyam S. Mohapatra, Ph.D., WAO Guest Editor, University of South Florida College of Medicine, Tampa, FL, USA , reviewed premier December medical journal articles for practicing allergists. Read his top 3 picks below and for the other 8 reviews, click here.
Shyam S. Mohapatra, Ph.D,WAO客座编辑,南佛罗里达大学医学院,坦帕,佛罗里达州,美国。他为在业的变态反应科医生回顾了十二月医学杂志的一些重要文章。下面是由他精选11篇摘要。

1. Abnormalities of the bronchial arteries in asthma.
This study compares the structure of the bronchial arteries, which supply systemic blood to the airways, tracheobronchial lymph nodes and nerves, in post-mortem lungs of three groups of subjects (n=12): one group with fatal asthma and death due to asthma, one group with fatal asthma and death not due to asthma, and one non-asthmatic group. In the two asthmatic groups, the intimal area was significantly larger than in the control group. Gender, age, smoking and duration of asthma were found to have significant effects on the intimal area in asthmatics. The increase in intimal area was associated with smooth muscle proliferation and reduplication and calcification of elastica but not with inflammatory cell infiltration. Editor’s Comments: This paper is interesting because quantitative analysis of bronchial arteries has not been done before. However, although the differences are statistically significant, the number of subjects in each group is small and the clinical significance of these findings in the context of severe or fatal asthma is unclear. Green  F.H.Y et al. Chest 2006;130 1025.
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1. 哮喘患者支气管动脉的异常
支气管动脉负责向气道、气管支气管淋巴结和神经输送血液,本研究比较了不同个体支气管动脉的结构差异。研究个体的肺脏分为三组 (n=12):一组为致死性哮喘个体且死因为哮喘,一组为致死性哮喘个体但死因非哮喘,另一组为非哮喘个体。在两组哮喘个体的支气管动脉内膜面积明显大于对照组。研究发现性别,年龄,吸烟以及哮喘病程对支气管动脉内膜面积均有显著影响。支气管动脉内膜面积的增加与平滑肌增生、弹力层钙化相关,但与炎性细胞浸润无关。编者按:本文章有趣之处在于首次支气管动脉进行了定量分析。尽管研究结果显示具有统计学差异,但由于每组研究对象数量偏少,其对重症或致死性哮喘的实际临床意义尚不清楚Green  F.H.Y et al. Chest 2006;130 1025.

2. Safety of trivalent inactivated influenza vaccine in children 6 to 23 months old.
This paper reports on the screening for medically attended events in the clinic, emergency department or hospital after administration of trivalent inactivated influenza vaccine to children 6-23 months old between 1991 and 2003 (45,356 children with 69,359 vaccinations). This is a retrospective cohort study using self-control analysis with chart review of vaccine data from significant medically attended events at eight managed care organizations in the United States . The primary endpoint was any medically attended event associated with administration of trivalent vaccine within the risk windows of 0-3 days and 1-14 days. All individual ICD-9 codes and predefined aggregate codes were examined. The results showed that 13 of 14 medical conditions including acute upper respiratory tract infection, asthma, bronchiolitis and otitis media were less likely to occur after vaccination. Only one condition, gastritis/duodenitis was more likely to occur after 14 days of vaccination; however, it was not significant after chart review. Editor’s Comments: This report is the largest study of the safety of vaccines in infants with a variety of medical conditions suspected of reacting adversely to vaccination. It clearly establishes that flu vaccination of infants in the presence of certain diseases, including upper respiratory tract infections, allergies and asthma, is safe. It should be pointed out, however, that this is a retrospective study based on medical records and not an actual trial. In addition, the results showed that the vaccine may cause gastritis, the reason for which is unclear. Hambidge SJ et al. JAMA 2006; 296:16: 1990-7.
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2. 对6到23月龄儿童应用三价灭活流感疫苗的安全性
本研究从门诊、急诊或医院收集了1991至2003年间,对6到23月龄儿童应用三价灭活流感疫苗后的发生的医疗事件(共45,356位儿童接受了69,359人次疫苗接种)。本研究属于回顾性队列研究,对来自美国8个管理保健组织提供的有意义医疗事件运用接种数据图表回顾进行了自身对照分析。初步研究终点为0-3天和1-14天窗口期内发生的任何与三价疫苗接种相关的医疗事件。分析所有个体的ICD-9 代码和预定义的整体编码。结果显示14种医学情况中有13种少见于疫苗接种后,包括急性上呼吸道感染,哮喘,细支气管炎和中耳炎。仅有胃炎/十二指肠炎较多见于疫苗接种14天以后;然而,经图表回顾未见显著性差异。编者按:该报告是关于婴幼儿疫苗接种安全性方面最大规模的研究,研究收集调查了疫苗接种后出现各种疑似疫苗不良反应的个体。研究表明对于那些患有某些疾病,包括上呼吸道感染、过敏性疾病和哮喘的婴幼儿接种流感疫苗是安全的。但需要指出,这项回顾性研究是基于医学记录而非真正的临床试验。另外,研究结果表明疫苗接种可能会引发胃炎,其具体机制不明。Hambidge SJ et al. JAMA 2006; 296:16: 1990-7.

3. Role of small airways in asthma: Investigation using high-resolution computed tomography.
Small airways may have an important role in asthma but their pathophysiological relevance remains unclear. Their condition is assumed to reflect air trapping and may be a useful noninvasive indicator of airway disease. The objective of this study was to use high-resolution computed tomography for evaluating lung density and to determine correlations with clinical and physiologic variables in 29 patients with stable asthma. Both lungs were scanned at full-inspiration and full-expiration to measure the percentage of lung occupied by low attenuation areas (LAA%;<-960 Hounsfield units) and the mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were also evaluated. The results showed that the mean lung density increased and LAA% decreased in all patients during the expiratory phase compared to the inspiratory phase. In conclusion, expiratory/inspiratory high-resolution computed tomography is useful for assessing small airway involvement in airflow obstruction, airway hypersensitivity and more severe diseases such as asthma. Editor’s Comments: HRCT can be very useful in diagnosing small airway disease. Tetsuya Ueda, MD J Allergy Clin Immounol 2006; 118:1019-25.
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3. 应用高分辨CT研究小气道在哮喘中扮演的角色
小气道可能在哮喘中扮演着重要角色,但是小气道的病理生理学意义尚不清楚。小气道状况可以用于反映肺内气体残留状况并可作为评估气道疾病的无创指标。本研究使用高分辨CT评估了29位稳定期哮喘患者肺组织密度,并观察临床指标和生理学变量之间的相关性。研究对所有肺脏在吸气末期和呼气末期进行高分辨CT扫描,测量低衰减区(LAA%;<-960汉斯菲得单位)的百分比和平均肺组织密度。同时评估哮喘严重程度,肺功能,乙酰甲胆碱气道敏感程度和反应程度,痰嗜酸细胞计数等指标。结果显示:与吸气相相比,所有患者在呼气相的平均肺组织密度增加、LAA%降低。总之,高分辨CT得到的呼气相/吸气相数值有助于对累及小气道疾病的评估,包括气流阻塞,气道高反应性以及更严重的疾病,如哮喘。编者按:HRCT有利于小气道疾病的诊断。 Tetsuya Ueda, MD J Allergy Clin Immounol 2006; 118:1019-25.

4. Successful management of mite-allergic asthma with modified extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae.
The objective of this prospective, double-blind, placebo-controlled study of 64 subjects was to evaluate the clinical efficacy and safety of a vaccine containing depigmented, polymerized allergens of Dermatophagoides pteronyssinus and D. farinae (equal amounts) in individuals diagnosed with mild to moderate asthma and rhinoconjunctivitis. The bronchial provocation test (BPT) was used to determine clinical efficacy. Among 54 patients who completed the study, the allergen-treated group experienced a significant improvement in BPT (p < 0.001), while the placebo group did not (p = 0.648). At the end of the study, allergen (n=20) vs. placebo (n=9) group (p=.013; odds ratio, 5.71[1.76, 18.51]) needed more than twice the amount of allergen to obtain a positive BPT. The active group showed median improvement of 53.76% in total symptom and 58.09% in medication scores over placebo. Thus, immunotherapy with a mixture of modified allergen extracts of D. pteronyssinus and D. farinae is safe and efficacious to treat mite-allergic asthma. Editor’s Comments: Although polymerized allergens have been tested in other allergies, there have been few reports on their use in dust mite therapy in mild/moderate asthmatics. This study demonstrates that polymerized allergen immunotherapy is safe and effective. Jose-Carlos Garcia-Robaina, MD, PhD J Allergy Clin Immounol 2006;118:1026-32
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4.应用屋尘螨和粉尘螨改良浸液成功治疗螨变应性哮喘
本研究为双盲,安慰剂对照前瞻性研究。目的:对64位诊断轻中度哮喘和鼻结膜炎的研究对象应用除色素屋尘螨和粉尘螨变应原多聚体进行免疫治疗,评估治疗的临床有效性和安全性。使用支气管激发试验(BPT)判断临床有效性。在54位完成研究的患者中,变应原治疗组的BPT数据明显改善(p < 0.001),而安慰剂组无改善(p = 0.648)。在试验终点,变应原治疗组 (n=20)与安慰剂组 (n=9) 相比(p=.013;比值比,5.71[1.76,18.51]) 需要两倍以上的变应原才能获得BPT阳性结果。治疗组与安慰剂组相比,总体症状评分改善53.76%,药物评分改善58.09%。因此,使用屋尘螨和粉尘螨改良变应原混合浸液对螨变应性哮喘患者进行免疫治疗是安全有效的。编者按:尽管变应原多聚体已试用于其他变应性疾病,目前尚无应用于轻中度螨变应性哮喘患者的报道。本研究证实使用变应原多聚体进行免疫治疗安全有效。Jose-Carlos Garcia-Robaina, MD, PhD J Allergy Clin Immounol 2006;118:1026-32

5. FceRI-mediated signal strength plays a key role in regulating basophil signaling and deactivation.
This study characterized the mechanisms for the control of FceRI-triggered basophil activation, which is a critical mediator of the symptoms of allergic disease and its underlying TH2-type response. Human basophils were purified by Ficoll density centrifugation and negative selection with immunomagnetic beads. Levels of various intracellular signal proteins were measured by Western blotting, and mediator release was analyzed either spectrofluorometrically (histamine) or by ELISA (IL-4 and IL-13). Supraoptimal anti-IgE concentrations led to lower mediator release than optimal concentrations but simultaneously to greater histamine release. In parallel, basophil signaling proteins (syk, p38 mitogen-activated protein kinase, and extracellular signal-regulated kinases 1 and 2) were more rapidly phosphorylated at higher anti-IgE concentrations but more transiently activated in the supraoptimal range. This regulation involved the inositol 5’ phosphatase, SHIP, which was phosphorylated with supraoptimal anti-IgE but not with lower concentrations. Basophils stimulated with N-formyl-methionylleucyl-phenylalanine failed to phosphorylate SHIP in the supraoptimal concentration range. Editor’s Comments: It appears that the kinetics of IgE-mediated signaling and mediator release in primary human FceRI+ cells varies substantially. This paper shows that the magnitude of stimulation and the phosphatase SHIP play an important role in terminating these events. Bernhard F. Gibbs, PhD. J Allergy Clin Immounol 2006; 118:1060-7.
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5. FceRI导的信号强度在调节嗜碱细胞信号传递和去激活中扮演关键角色
本研究描述了FceRI 触发嗜碱细胞活化的调控机制,FceRI对嗜碱细胞的激活是引发变应性疾病及其内部TH2型免疫应答相关症状的重要媒介。人嗜碱细胞经过Ficoll密度梯度离心法纯化处理以及免疫磁珠阴性选择处理。应用蛋白质印迹法(Western blotting)测量细胞内不同信号蛋白的水平,使用萤光分析法(组胺)或ELISA(IL-4和IL-13)技术分析介质释放情况。与适量抗IgE浓度相比,超适浓度抗IgE能进一步减少炎性介质的释放,但两种情况都会加重组胺的释放。嗜碱细胞信号蛋白(syk,p38 丝裂原活化蛋白激酶和细胞外信号调节激酶1、2) 在较高抗IgE浓度下可以发生磷酸化,但在超适浓度范围内的激活效应持续时间更短。肌醇 5’ 磷酸酶(SHIP)参与了该调节过程,SHIP可以在抗IgE超适浓度下发生磷酸化,而低浓度时则无反应。在超适浓度范围内,嗜碱细胞受甲酰蛋氨酰亮氨酰苯丙氨酸(N-formyl-methionylleucyl-phenylalanine,fMLP)刺激无法对SHIP进行磷酸化。编者按:看起来人FceRI+原始细胞中IgE导信号动力学以及介质释放的变异相当大。该研究表明刺激程度和磷酸酶SHIP 对这些反应的终止起了重要作用。Bernhard F. Gibbs, PhD. J Allergy Clin Immounol 2006; 118:1060-7.

6. Sequence, haplotype, and association analysis of ADRB 2 in multiethnic asthma.
This study identified ADRB2 polymorphisms and haplotypes in White and African American subjects and correlated them with asthma phenotypes. A 5.3 kb region of ADRB2 was sequenced in 669 individuals --429 Whites and 240 African Americans. Twelve polymorphisms, representing an optimal haplotype tagging set, were genotyped in Whites (338 patients and 326 control subjects) and African Americans (222 patients and 299 control subjects). The study identified 49 polymorphisms, 21 of which were novel. Thirty-one polymorphisms (frequency > 0.03) were used to identify 24 haplotypes (frequency > 0.01) and assess linkage disequilibrium. An association of genotype with the ratio FEV1/FVC was observed in African Americans. This report demonstrates that additional genetic variants besides +46 (Gly16Arg) are important in determining asthma phenotypes. For example, the length of a poly-C repeat (+1269) in the 3’ untranslated region of ADRb2 may influence lung function and may account for variation in b-agonist responses, especially in African Americans. Editor’s Comments:  A comprehensive evaluation of gene variation, haplotype structure, and linkage disequilibrium is important in understanding the influence of the b2-adrenergic receptor gene ADRB2 on disease susceptibility, pulmonary function, and therapeutic response in different ethnic groups with asthma. This study demonstrates that there are additional ADRB2 genetic variants besides +46 (Gly 16 Arg) and +79 (Gln 27 Glu) that are important in determining asthma phenotype. Gregory A Hawkins AM J Respir Crit Care Med Vol 174 20061101-1109, 2006.
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6. 不同种族哮喘患者的ADRB2序列,单体型及相关分析
本研究确定了美国白人和非裔个体ADRB2的多态性和单体型,并观察了与哮喘显型的相互关系。对669位患者对ADRB2的5.3 kb区域进行了蛋白质测序,包括429名美国白人和240名非裔美国人。代表最佳单体型标注集的12种多态性见于白人个体(338位患者和326位对照个体)和非裔个体(222位患者和299位对照个体)中的基因型。本研究共确认了49种多态性,其中有21种是新发现的。共有31种多态性(频率>0.03)被用于确定24种单体型(频率>0.01)以及连锁不平衡的评估。研究在非裔美国人中发现了基因型和FEV1/FVC之间有关联。本报告证实除+46 (Gly16Arg)之外的其它基因变化对决定哮喘显型有重要意义。例如,ADRb2非编码区域的poly-C重复的长度(+1269)可能对肺功能产生影响,同时可能解释了b-激动剂应答的多样性,特别是对非裔美国人而言。 编者按: 对于理解b2-肾上腺素能受体基因ADRB2对不同人种哮喘患者疾病易感性、肺功能以及治疗反应的影响,对基因变异、单体型结构以及连锁不平衡进行全面评估是非常重要的。本研究证实在+46 (Gly 16 Arg) 和+79 (Gln 27 Glu) 之外还有另一个ADRB2 基因变异对确定哮喘显型意义重大。Gregory A Hawkins AM J Respir Crit Care Med Vol 174 20061101-1109, 2006.

7 Polymorphisms in the muscarinic receptor 1 gene confer susceptibility to asthma.
Here the authors investigated the role in asthma of the human cholinergic receptor muscarinic-1 (CHRM1) gene located on chromosome 11q13. The receptor is widely distributed in the lungs and may be involved in airway constriction, epithelial cell proliferation and inflammation. In a case-controlled study using 326 Japanese patients with asthma and 333 healthy control subjects, 9 single-nucleotide polymorphisms in the CHRM1 gene were examined. The functional consequences of the -9697C > T and -4953A > G polymorphisms at the regulatory region were also determined using an mRNA reporter assay, which suggested associations with asthma. Haplotype analysis showed that the -9697T/9695T/ -4953A haplotype was associated with a lower risk of asthma (p= 0.00055) and the 9697C/-6965T/ -4953G haplotype was associated with an increased risk of asthma (p=0.020). The -9697T/ -4953A haplotype was also associated with lower luciferase activity in vitro compared with the 9697C/ -4953G haplotype. Taken together, these results suggest that the CHRM1 gene on chromosome 11q13 is an important determinant for susceptibility to asthma. Editor’s Comments: Since the beginning of asthma genetic studies, several candidate genes linked to asthma phenotypes have been found at the 11q13 locus. This study demonstrates that CHRM1, which is also at 11q13, is an important susceptibility gene for asthma. Yukiko Maeda Am J Respir Crit Care Med Vol 174 2006 1119-1124.
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7毒蕈碱样乙酰胆碱受体1基因多态性赋予哮喘易感性
文章作者研究了人乙酰胆碱能毒蕈碱样受体-1(CHRM1)在哮喘的作用,其基因位于染色体11q13上。该类受体广泛分布在肺组织并有可能参与气道收缩、上皮细胞增生和炎症过程。一项病例对照研究共对326名日本哮喘患者和333名健康个体CHRM1基因中9个单核苷酸的多态性进行了调查。使用mRNA 报告检测方法确定 -9697C > T 和 -4953A > G在调控区多态性的功能性结果,这能提示与哮喘的关联性。单体型分析显示-9697T/9695T/ -4953A单体型与哮喘低风险相关(p= 0.00055),而 9697C/-6965T/ -4953G单体型与哮喘高风险相关(p=0.020)。体外试验显示,与 9697C/ -4953G单体型相比,-9697T/ -4953A单体型还与荧光素酶低活性相关。总之,这些结果表明染色体11q13上的CHRM1基因对于哮喘易感性具有重要决定意义。编者按:自哮喘基因学研究开始至今,人们在11q13位点上发现数个与哮喘显型相关的候选基因。本研究证实同样位于11q13的CHRM1也是一个重要的哮喘易感基因。Yukiko Maeda Am J Respir Crit Care Med Vol 174 2006 1119-1124.

8. A3 adenosine receptor signaling contributes to airway mucin secretion after allergen challenge.
Mucus hypersecretion is characteristic of asthma, but the cellular and molecular mechanisms that regulate mucin production and secretion are poorly understood. This study uses genetics to investigate the contribution of the A3 adenosine receptor, A3AR, to mucus production and secretion in a mouse model of allergen-induced pulmonary disease. A3AR is part of a signaling pathway that is upregulated in the mucin-producing goblet cells of the airway, but mucin production in response to allergen is similar in wild-type and A3AR-deficient mice. Overexpression of this receptor in Clara cells neither induces mucin production itself nor enhances mucin production in response to allergen challenge, and A3AR is not required for mucus cell metaplasia. In contrast to the lack of effect on mucin production, agonist-induced mucin secretion was reduced in A3AR-deficent mice. Thus, mucin secretion induced by allergen treatment is stimulated via A3AR. In pulmonary disorders in which adenosine levels are elevated, signaling through this receptor may contribute to airway obstruction by mucus. Editor’s Comments: Mucus production and secretion in the airway is a complex phenomenon, and this study shows that the two processes are distinct. A3AR signaling does not affect mucus production but does promote mucus secretion. This is important since adenosine levels in the lung are increased as a result of inflammation and damage. Hays W. J. Young Am J Respir Cell Mol Biol Vol 35 2006 549-558.
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8. 腺苷受体A3信号促使气道在变应原激发后分泌粘液
粘液过量分泌是哮喘的特征之一,但是有关调节粘液生成和分泌的细胞分子学机制知之甚少。本研究对变应原诱导肺疾病的小鼠模型运用遗传学手段研究腺苷受体A3(A3AR)对粘液生成和分泌的作用。A3AR属于气道粘液生成杯状细胞中上调信号通路的一部分,但是在野生型和A3AR缺陷型小鼠模型中变应原引起粘液的生成量相似。该受体在Clara 细胞中的过表达既不会引起粘液生成,也不会增强因变应原激发导致的粘液生成,而A3AR也不是粘液细胞分化的必要因素。在A3AR 缺陷型小鼠中,激动剂诱导的粘液分泌降低,但粘液生成量不受影响。因此,变应原治疗诱发的粘液分泌是通过刺激A3AR实现的。在肺疾病个体中腺苷水平上升,由A3AR 传递的信号可能通过影响粘液造成气道的阻塞。编者按:气道中粘液的生成和分泌非常复杂,本研究表明这是两个截然不同的过程A3AR 信号并不影响粘液的生成,但却可以促进粘液的分泌。这个发现很重要,因为炎症损伤可以导致腺苷在肺组织的水平升高。Hays W. J. Young Am J Respir Cell Mol Biol Vol 35 2006 549-558.

9. Respiratory syncytial virus infection reduces B2-adrenergic responses in human airway smooth muscle.
This study addresses the hypothesis that respiratory syncytial virus (RSV) has direct effects on cAMP formation and B2-adrenergic receptor (ADRβ2) density and that the ADRβ2 haplotype influences this response. A recombinant RSV expressing green-fluorescent protein (rgRSV) was first used to determine whether RSV could infect cultured human airway smooth muscle cells (HASM). Then, the influence of RSV infection on β2-adrenergic responsiveness was determined by measuring differences in isoproterenol (ISO)-induced cyclic AMP (cAMP) formation, ADRβ2 density and Gi expression in HASM cells infected with RSV, with ultraviolet-inactivated RSV, or with vehicle. The cultured HASM cells were efficiently infected by RSV, and ISO-induced cAMP formation was significantly reduced in RSV-infected cells, compared to cells infected with ultraviolet-inactivated RSV or mock-infected, in a time- and concentration-dependent manner. Forskolin-induced cAMP formation and Gi expression were not altered in cells infected with RSV, suggesting that the influence of RSV on β2-adrenergic relaxation was upstream of cAMP formation. ADRβ2 density was reduced in cells infected with RSV and the Arg16Gln27 ADRβ2 haplotype was associated with decreased ISO-induced cAMP formation (p<0.05) and with decreased ADRβ2 density at baseline (p<0.05).  Editor’s Comments: The use of b2-agonists in the treatment of airway obstruction associated with RSV infection has been controversial. The results of this study show that β2-agonist effects may be related to direct effects of RSV on HASM, and that the ADRβ2 genotype may predict bβ-adrenergic responses. Paul E. Moore Am J Respir Cell Mol Biol Vol 35 2006 559-564.
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9. 呼吸道合胞病毒感染可以降低人气道平滑肌β2-肾上腺素能的应答
本研究提出这样一个假设:呼吸道合胞病毒(RSV)可以直接影响cAMP 的形成以及β2-肾上腺素能受体(ADRβ2)密度,而ADRβ2单体型可以影响这个作用。重组RSV表达绿色萤光蛋白(rgRSV)是第一个用于测定RSV是否能感染人工培养的人气道平滑肌细胞(HASM)。RSV感染对β2-肾上腺素能应答的影响可以通过测量使用RSV、紫外线灭活RSV或质粒感染的HASM 细胞中以下指标的差异来确定:异丙肾上腺素(ISO)诱导环磷酸腺苷(cAMP)的生成,ADRβ2密度以及Gi 的表达。人工培养HASM细胞可以充分被RSV感染,与紫外线灭活RSV感染或者假感染的细胞相比,在RSV感染的细胞中ISO诱导cAMP生成明显减少,这一现象具有时间依赖性和浓度依赖性。Forskolin诱导的cAMP生成和Gi 表达在RSV感染的细胞中无变化,提示RSV对β2-肾上腺素能松弛作用是在cAMP形成的上游。ADRβ2密度在RSV感染的细胞中降低;Arg16Gln27 ADRβ2单体型不但与ISO诱导cAMP生成减少相关(p<0.05),还与ADRβ2密度的降低相关(p<0.05)。编者按:使用β2-激动剂治疗与RSV感染相关的气道阻塞一直存在争议。该研究结果显示β2-激动剂效应可能与RSV对HASM 的直接作用存在关联,ADRβ2基因型也许能用于β-肾上腺素能反应的预测。 Paul E. Moore Am J Respir Cell Mol Biol Vol 35 2006 559-564.

10. Airway hyperreactivity in exacerbation of chronic asthma is independent of eosinophilic inflammation.
The authors of this report have developed an animal model to investigate the mechanisms underlying an acute exacerbation of chronic asthma. Ovalbumin (OVA)-sensitized BALB/c mice were exposed to aerosolized OVA, either as a chronic low-level challenge for four weeks, a single moderate-level challenge, or chronic low-level followed by single moderate-level challenge (the acute exacerbation group). Compared with animals receiving chronic challenge alone, mice in the acute exacerbation group exhibited more marked inflammation, with involvement of intrapulmonary airways and lung parenchyma, and increased numbers of lymphocytes and eosinophils in bronchoalveolar lavage fluid. They also developed airway hyperreactivity (AHR) to methacholine, demonstrable as increased transpulmonary resistance and decreased compliance. This pattern of AHR was absent in chronically challenged animals but was present in animals given a single moderate-level challenge. However, compared with animals receiving a single moderate-level challenge, inflammation and AHR were induced more rapidly in the acute exacerbation group. Eosinophil-deficient GATA1 dbl mice exhibited undiminished AHR in the acute exacerbation model. Thus, mice with pre-existing airway lesions resembling mild chronic asthma, when exposed to a moderately high concentration of inhaled antigen, experience the symptoms of an acute exacerbation. The inflammatory response involves distal airways and is associated with a distinct pattern of AHR, which develops independently of the enhanced eosinophilia. Editor’s Comments: Eosinophilia has been considered the hallmark of allergic asthma. This study shows that the extent of airway hyperreactivity and eosinophilia actually depends upon the magnitude of antigen exposure in a specific state of the disease. Thus, chronic asthma can be devoid of eosinophilia.  Jessica S. Siegle Am J Respir Cell Mol Biol Vol 35 2006 565-570.
译文
10. 慢性哮喘急性发作的气道高反应性不依赖于嗜酸细胞炎症
本报道的作者们开发了一种动物模型来研究慢性哮喘急性发作的可能机制。将卵清蛋白 (OVA)-致敏的BALB/c小鼠暴露于雾化OVA:或者给予低剂量的OVA持续激发4周,或者给予单次中等剂量激发,或者在低剂量的OVA持续激发后给予单次中等剂量激发(急性发作组)。与仅接受OVA慢性激发的动物相比,在急性发作组小鼠可以观察到更多典型炎症表现,炎症累及肺内气道和肺实质,在支气管肺泡灌洗液中的淋巴细胞和嗜酸细胞数目增多。通过乙酰甲胆碱检查还发现急性发作组小鼠出现气道高反应性(AHR),其肺间阻力升高,同时肺顺应性降低。慢性OVA激发组小鼠无AHR ,而给予单次中等剂量激发组小鼠出现AHR 。但是,与接受单次中等剂量OVA激发组小鼠相比,急性发作组小鼠可以更快诱导产生炎症和AHR 。使用嗜酸细胞缺陷GATA1 dbl小鼠制作急性发作模型也可以产生持续的AHR。而将预制有类似轻度慢性哮喘气道损伤的小鼠暴露于高浓度吸入抗原,也可以出现哮喘急性发作的症状。炎症应答涉及远端气道并与AHR相关,但AHR的出现并不依赖于是否存在嗜酸细胞增多。编者按:嗜酸细胞增多症一直被认为是变应性哮喘的标志。本研究显示气道高反应性和嗜酸细胞增多的程度事实上依赖于在疾病特定时期机体暴露于抗原的数量。因此,慢性哮喘可以不伴有嗜酸细胞的增多。 Jessica S. Siegle Am J Respir Cell Mol Biol Vol 35 2006 565-570.

11.  Role of epithelial damage and angiogenesis in childhood asthma.
Airway remodeling and inflammation are characteristic features of adult asthma that have been little studied in childhood asthma. This study examines epithelial and vascular changes as well as the inflammatory response in airways of asthmatic children. The study analyzed bronchial biopsies obtained from 44 children undergoing bronchoscopy for clinical indications other than asthma: 17 had mild to moderate asthma (aged 2-25 yr), 12 had atopy without asthma (1-11 yr), and 15 were controls without atopy or asthma (1-14 yr). Epithelial cell loss, basement membrane thickness, number of vessels and inflammatory cells were quantified in sub epithelium by histochemisty and immunohisto-chemisty. The results showed increased epithelial loss and basement membrane thickening in children with asthma compared to controls (p = 0.005 and 0.0002, respectively) and atopic children (p = 0.002 and 0.005, respectively). The number of vessels and eosinophils was increased in asthmatic children (p = 0.03 and p = 0.0002, respectively) and in atopic children without asthma (p = 0.03 and p = 0.008, respectively) compared to controls. When the results were stratified according to age, the children younger than six years with asthma had increased epithelial loss, basement membrane thickening, and eosinophilia compared to controls of the same age. In conclusion, epithelial damage and basement membrane thickening, which are characteristic pathologic features of adult asthma, are present even in childhood asthma. Other changes, such as airway eosinophilia and angiogenesis were also observed in atopic subjects suggesting that they may represent early events in the natural history of asthma. Editor’s Comments: This is an excellent study essentially showing that childhood asthma is not significantly different from adult asthma. Angelo Barbato Am J Respir Crit Care Med Vol 174 2006 975 -981
译文
11.  气道上皮损伤和血管生成在儿童哮喘中的作用
气道重塑和炎症被证实是成人哮喘的典型特征,但在儿童哮喘中的相关研究甚少。本研究调查了儿童哮喘患者气道中上皮和血管的改变以及炎症应答。研究分析44位因其他疾病接受支气管镜检的儿童患者的活检标本:其中17位患轻中度哮喘(2-25岁),12位患特应性疾病但无哮喘(1-11岁),另外15 位对照病例既无哮喘也无特应性疾病(1-14 yr岁)。研究中使用组化技术和免疫组化技术对上皮细胞丢失,基底膜增厚,上皮下血管和炎性细胞数目进行统计。结果显示:与对照组相比,哮喘儿童组上皮细胞丢失和基底膜增厚情况加重(p值分别为0.005和0.0002),无哮喘的特应性儿童组有同样变化(p值分别为0.002和0.005)。与对照组相比,哮喘儿童组上皮下血管和嗜酸细胞数目增加(p值分别为0.03和0.0002),无哮喘的特应性儿童组有同样变化(p值分别为0.03和0.008)。如果将结果根据年龄分层,与对照组相比,可以看到小于6岁哮喘个体的上皮细胞丢失增多,基底膜增厚加重,嗜酸细胞数目增加。总之,做为成人哮喘典型病理学特征的上皮细胞损害和基底膜增厚也可见于儿童哮喘。其它改变,例如气道嗜酸细胞增多和血管生成也可见于特应性疾病个体,提示这些改变可能是哮喘自然病程中的早期事件。编者按:该研究主要说明儿童哮喘与成人哮喘相比没有明显的区别。Angelo Barbato Am J Respir Crit Care Med Vol 174 2006 975 -981


WAO Now: What's New in the World of WAO 今日WAO:WAO领域新进展

gloria2007 February GLORIA Placements
2007
年2月 GLORIA安排

The 5th International Congress of the
Egyptian Society of Pediatric Allergy & Immunology

埃及儿科变态反应及免疫学学会第5届国际会议
February 8-9, 2007
Giza, Egypt
International GLORIA Faculty:
国际GLORIA教员:
Michael A. Kaliner
Presentation:
主讲:
Module 8: Anaphylaxis
第8单元:严重过敏反应
http://www.espai-eg.org/

San Diego Allergy Society
圣地亚哥变态反应学会
February 12, 2007
2007 年2月12日
San Diego, California
圣地亚哥,芝加哥州
US GLORIA Faculty:
美国GLORIA教员
Allen P. Kaplan
Presentation:
主讲:
Module 7: Angioedema
第7单元:血管神经性水肿

GLORIA is supported through unrestricted educational grants from:

GLORIA得到以下公司教育资助的支持

alcon

dey

dyax & genzyme

nutricia  shs

schering-plough


seminars and conferencesFebruary 2007 Seminars & Conferences Placement
2007
年2月研讨会安排

Regional Asthma Congress - Egyptian Society of
Allergy and Clinical Immunology
地区性哮喘大会-埃及变态反应和临床免疫学学会
January 31 – February 2, 2007
Hurgada, Egypt
WAO Invited Lecturer:
WAO特邀讲者:
Michael A. Kaliner
http://www.asthmaegypt2007.com/


world allergy forum World Allergy Forum
世界变态反应论坛

"A Global Perspective on Genetics, the Environment and Allergy"
遗传学,环境学和变态反应学的全球展望

2007 AAAAI Annual Meeting
2007AAAAI
年会
Monday, February 26, 2007, 4:45 pm - 6:00 pm
San Diego Convention Center
Upper Level, Room 32 AB

Moderator:
主持人:
Thomas A. E Platts-Mills, USA

Co-Moderator:
共同主持人:
Michael A. Kaliner, USA

Is Early Exposure to Allergen Protective?
变应原早期暴露具有保护作用?
Adnan Custovic, United Kingdom

How Does the Environment Influence Genetic Responses?
环境怎样影响遗传应答?
Robert F. Lemanske Jr., USA

Environmental Intervention in the Management of Allergic Diseases
变应性疾病控制中的环境干涉
Erika Von Mutius, Germany


WAO Conversations

WAO会话

We have the pleasure of announcing four new interviews with well-respected allergists.  Take a moment to listen to them share their extensive knowledge.
很高兴地宣布下面我们有对四位著名变态反应学专家访谈记录。邀请您来分享他们广袤的知识。

  • Prof. Jean Bousquet -- WHO-GARD: The global alliance against chronic respiratory diseases
    Jean Bousquet 教授 -- WHO-GARD:对抗慢性呼吸系统疾病全球联盟
  • Prof. Paul Van Cauwenberge -- Allergic Rhinitis: A disease remodeling the upper airways?
    Paul Van Cauwenberge教授 -- 变应性鼻炎:重塑于上呼吸道的疾病?
  • Prof. G. Walter Canonica -- Real life classification of allergic rhinitis
    G. Walter Canonica教授 --变应性鼻炎的实际生活分级
  • Dr. Ronald Dahl - Allergenic Cross Reactivity
    >Ronald Dah博士 – 变应原的交叉反应性


WAO Committees and Councils 2007: A Year in Review and plans for the future
WAO委员会和理事会2007:过去一年的回顾以及将来的计划

Research Council
The year 2006 saw the selection and successful completion of the first three WAO Short-Term Research Fellowships and the selection of the first WAO Long-Term Research Fellow. As we move into 2007 WAO will consider major epidemiological surveys of allergic disease, look in-depth at the management of anaphylaxis worldwide, and publish the Allergy Prevalence Survey responses of our member societies.
研究委员会
2006年我们挑选并圆满完成前三项WAO短期研究基金资助项目,完成首项WAO长期研究基金资助项目的挑选工作。进入2007年,WAO将进行主要变应性疾病的流行病学调查,深入开展世界范围内严重过敏反应的治疗工作,出版来自成员学会的变应性疾病患病率调查反馈。

Education Council
We have surveyed our membership to ascertain the educational needs of our constituents and placed GLORIA™ and Seminars and Conferences programs in every region of the World. World Allergy Forum symposia were presented at EAACI, AAAAI and ACAAI. This high level of activity will continue worldwide with three Seminars and Conferences programs, 28 GLORIA programs, and two World Allergy Forum symposia in 2007.
教育委员会
我们通过调查明确了会员的教育需求,在全世界范围内安排了GLORIA™、研讨会和大会。我们在EAACI,AAAAI和ACAAI上举办了世界变态反应论坛。2007年,高水平活动将继续在世界范围内举办:包括三个研讨会和大会,28个GLORIA活动以及两个世界变态反应论坛。

Specialty and Training
In 2006, the WAO Specialty and Training Council published its report "“Allergy Practice Worldwide" and also "Requirements for Physician Training in Allergy: Key Clinical Competencies Appropriate for the Care of Patients with Allergic or Immunologic Diseases - A Provisional Position Statement of the World Allergy Organization." The third document in this series, "What is an Allergist?," will be published early in 2007. These documents already are providing an important reference source for our member societies and helping them to promote our specialty on a global level.
专业培训
2006年WAO专业培训委员会发布了两份报告:“全世界变态反应专业”和“变态反应学医师培训要求:具备治疗变态反应或免疫疾病的关键临床能力 - 世界变态反应组织临时性指导报告”。该系列报告的第三份“什么是变态反应专家?”将在2007年早些时候发布。这些文件为我们的会员学会提供了重要参考资料,帮助他们以全球统一标准提高专业人员的水平。

Communication Council
Web site initiatives saw the launching of WAO Conversations and Interactive Case Reviews and the monthly e-letter being translated into seven languages. On the horizon for the Web site in 2007 will be a series of Web-based seminars (in conjunction with AAAAI), Ask the Expert and an online Membership Directory. 
通讯委员会
WAO网站已经开始刊登WAO访谈录,互动式病例回顾,以及翻译成数国语言的每月电子通讯。2007年网站工作将推出:系列网络研讨会(与AAAAI联合),专家答疑以及在线会员字典。

Emerging Societies
In 2006, we achieved significant progress in the Emerging Societies Program. We placed pollen traps in the CIS Region and are developing a WAO Aeroallergen Sampling Manual to support this program. The Emerging Societies Meeting in Buenos Aires produced valuable insight into allergy practice in the underserved areas of Latin and Central America; we are moving forwards with the assistance of our member societies in the region and in collaboration with ACAAI, AAAAI and the National Institutes of Health in the USA , to help our fellow allergists in these countries. 2007 will see an ESM in Bangkok for our colleagues in the Asia Pacific region, in association with a new ESM partner, the Western Pacific Allergy Organization.
新兴学会
2006年我们在新兴学会规划方面取得了重大进展。我们在CIS地区安置了花粉收集装置,并制定了WAO气传变应原采样指南对该项目予以扶持。在布宜诺斯艾利斯召开新兴学会会议(ESM)对拉丁美洲、中美洲欠发展地区的变态反应工作进行了了解。通过该地区会员学会的协助,以及与ACAAI、AAAAI和美国国立卫生研究院的合作,我们进一步资助了在这些国家的WAO会员。2007年,我们将联合ESM新伙伴-西太平洋变态反应组织,在曼谷举办亚洲、泛太平洋地区的ESM。


Sign up for On-Line Journal Subscription –
在线杂志订阅申请-

WAO and Hogrefe & Huber Publishers are offering a limited number of free on-line subscriptions to Allergy & Clinical Immunology International - Journal of the World Allergy Organization for members in developing countries. If you are interested in receiving a complimentary, on-line subscription, please send an e-mail to info@worldallergy.org, noting “Free Journal Subscription” in the subject line, with the following details:

First name
Last name
Postal address
City, State/Province and postal code
Country
E-mail address
Name of Member Society

WAO和Hogrefe & Huber出版公司现为发展中国家的会员提供有限数量的《Allergy & Clinical Immunology International - Journal of the World Allergy Organization免费在线订阅服务。如果您希望得到这份杂志的免费赠阅的电子版,请给我们发送e-mail至info@worldallergy.org,注意在信件的主题栏写“Free Journal Subscription”,并详细注明以下资料:

名字
姓氏
邮政地址
市,州/省和邮政编码
国家
E-mail地址
成员学会的名称


And In Other News 其他新闻

Allergy Book Reviews
变态反应学书评

Concise Clinical Immunology for Healthcare Professionals
简明临床免疫学(医疗专业)
Mary T Keogan, Eleanor M. Wallace, and Paula O’Leary
ISBN: 9780415298308
ISBN-10: 041529830X

List Price: £25.99 (about $50.00 USD)
定价:25.99英镑(约50.00美元)
Available from: Taylor and Francis Books
订购网址:Taylor and Francis Books

Reviewer:
Thomas Chacko, MD, 2nd year Fellow
University of South Florida College of Medicine, Tampa, FL
书评作者:
Thomas Chacko, MD, 第二年研究员
南佛罗里达大学医学院,坦帕,佛罗里达州

Description:
This text is a concise and easy to access manual about the complex field of clinical immunology.
说明:
对复杂的临床免疫学领域而言,该书是本简洁易懂的入门指南。

Purpose:
The purpose of this book is to provide the physician and other healthcare professionals with an introductory book on clinical immunology. It also covers basic immunology, laboratory investigations and the treatment of various immunological disorders.
目的:
本书目的在于为内科医师和其他医务工作者提供一本临床免疫学介绍性读物。书中涉及的有:基础免疫学,多种免疫疾病的相关实验室研究和治疗。

Audience:
This book is geared toward the novice student, the first year sub‑specialty resident in allergy and immunology, and other physicians who want to learn basic immunology as it impacts clinical immunology. It provides the key features without getting lost in details.
读者:
本书面向初学者,变态反应和免疫学专科初年住院医师,以及其他希望学习基础免疫学及临床免疫学的内科医生。本书在突出重点同时又做到了不失细节。

Features:
The book's 426 pages are divided into four chapters: basic immunology, clinical immunology, immunotechniques and diagnostic testing, and treatment of immunological disorders. Each chapter has multiple, 2-4-page sections on various subjects within a chapter. At the end of some sections, there are references for further reading. There are also various diagrams and a self‑assessment test at the end of each chapter. Case presentations (14 total) are dispersed within some chapters.
特色:
本书426页,分为4章:基础免疫学,临床免疫学,免疫学技术和诊断方法,免疫疾病的治疗。每章根据不同内容分节不等,每节2-4页。在部分节后留有可供进一步学习的参考书目。在每章后都罗列了大量图表和一份自评测试。全书还提供了总共14份病例讨论。

Assessment:
This is an excellent book on the basics of clinical immunology. The sections are arranged to allow for quick retrieval of key facts. The self‑assessment exams keep the reader actively thinking to emphasize salient information. Other sources are necessary for a more in-depth review of this complex subject, but this is a great start, even for those with considerable skills in these areas.
评价:
这是一本关于临床免疫学基础的优秀图书。本书章节安排有序,读者可以迅速对所需关键内容进行检索。书中的自评测试可以帮助读者积极思考书中强调的重要内容。临床免疫学是一门复杂的学科,我们固然需要更多的学习资料以便对其进行深入研究,但即使对于那些已在该领域具备一定相关技能的读者,本书仍不失为一本优秀的启蒙读物。

In summary, this book will be particularly helpful for the novice student or physician who wants to learn about clinical immunology.
简而言之,本书将对那些希望掌握临床免疫学的初学者或内科医师大有裨益。

Cystic Fibrosis in the 21st Century
在21世纪的囊性纤维化
Bush, A., Alton, EWFW., Davies, JC., Griesenbach, U. & Jaffe, A.
ISBN-10: 3-8055-7960-8
ISBN-13: 978-3-8055-7960-5

List price: $180.00 USD
Available from: Karger
定价:180.00美元
订购网址:Karger

Reviewer: 
Dr RG Stirling BSc(Hons), MBBCh(Hons), MRCPI, FRACP
Department of Allergy Immunology & Respiratory Medicine; Alfred Hospital & Monash University; Melbourne, Australia
书评作者:
Dr RG Stirling BSc(Hons), MBBCh(Hons), MRCPI, FRACP
变态反应、免疫学&呼吸内科;南侨医院&莫纳什大学;墨尔本;澳大利亚

Description:    
Recent decades have seen an explosion of knowledge in Cystic Fibrosis (CF), surrounding CFTR structure, function and the mechanism by which this gene defect causes human disease. This book addresses these developments in some detail, yet also broadly scopes a range of current CF-related research activity. Further in-depth consideration is given to the challenge of clinical care in relation to airway infection, inflammation and the management of the extrapulmonary manifestations of CF.
说明:
近数十年来,在囊性纤维化(CF)领域相关知识不断得到拓新:CFTR结构、功能,因基因缺陷导致发病的机制。本书较为详细的介绍了上述内容的进展,并对当前CF相关科研工作进行了介绍。需要对与气道感染、炎症相关临床治疗和CF肺外表现治疗方面所面临的难题予以更深的研究。

Purpose:         
A state of the art overview of recent advances in Cystic Fibrosis.
目的:
概括近年来在囊性纤维化领域取得的新进展。

Audience:       
This volume is largely aimed at researchers and clinicians established in CF, needing to update and broaden their understanding of CF.
读者:
该书主要面向那些需要更新拓宽CF相关知识的研究人员和临床工作者。

Features:        
This book acknowledges the multidisciplinary approach necessary for advancing CF care by blending a strong scientific base to the broad clinical needs of the CF population. Edited and written by leading figures in CF research, this volume highlights developments in understanding of CFTR structure and function, yet provides useful updates in the key management and therapeutic questions for pediatric and to a lesser degree adult CF care.
特色:
本书强调了提高CF医疗工作必要的多学科方法,该方法能将扎实的科研基础与CF患病人群诸多临床需求结合在一起。本书编写人员均是CF研究领域的领军人物,这本书着重介绍了CFTR结构和功能方面的进展,但同时也为儿科医师、成人CF的低年资医护人员提供了医疗护理知识方面的有益更新。

Assessment:    
This volume places substantial emphasis in the description of current knowledge of CFTR structure, function and their interrelationships. The interactions and significance of genotype, modifier genes, infection and inflammation provide many complex challenges to our understanding of CF, and this book also provides a broad yet succinct research update in a number of these areas. For the practicing clinician, however, CF in the 21st century is evolving as a disease of adulthood and many emerging adult medical issues including bone disease, GORD, non-invasive ventilation and the complex management challenges of airway clearance, psychosocial counselling, ethics, transition, palliation and transplantation, require further attention. Nevertheless, this volume provides a valuable supplement and addition for those seeking to update and broaden their understanding of Cystic Fibrosis.
评价:
这本书着重介绍了有关CFTR结构、功能及其相互关系的最新知识。书中关于基因型相互作用和意义、修饰基因、感染和炎症的内容使我们在CF的理解方面面临一定挑战,该书还在很多方面为读者提供了广博而简明的最新科研信息。对于临床医生需要注意的是,21世纪的CF不仅是一种成人疾病,还涉及了许多新出现的成人问题:骨病,>GORD,气道清理中无创通气和治疗的挑战,心理咨询,伦理,转变,减轻(痛苦)以及移植,这些都需要给予深入关注。尽管如此,这本书为那些渴望更新拓宽自身对囊性纤维化相关知识的读者提供了有益帮助。

Find more allergy book reviews on the WAO Website here.
WAO网站上其它的变态反应学书评见此处

The World Allergy Organization's mission is to build a global alliance of allergy societies to advance excellence in clinical care, research, education and training. Visit us on the Web at http://www.worldallergy.org/
世界变态反应组织的使命是建立一个全球性的变态反应学会联盟,不断推动临床、科研、教学与培训工作的进步。欢迎您浏览我们的网站: http://www.worldallergy.org/

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Milwaukee, WI 53202-3823
Email: info@worldallergy.org
世界变态反应组织(WAO)秘书处
555 E. Wells Street, Suite 1100
Milwaukee, WI 53202-3823
电子信箱:info@worldallergy.org

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您因如下原因收到此次通讯:您是世界变态反应协会会员,或者您曾向世界变态反应协会订阅过电子月刊,或者您以前曾与世界变态反应协会进行过有关联系。如果您不希望继续收到来自世界变态反应协会的信息,请以“>删除”为主题回复此邮件。

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