WAO News and Notes - Medical Reviews
Volume 5, Issue 8 Reviews - August 2008
Medical Journal Reviews

Reviewed by Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief

1. Comparison of adjustable-and fixed-dose budesonide/formoterol (BF) pressurized metered-dose inhaler and fixed-dose fluticasone propionate/salmeterol (FS) dry powder inhaler in asthma patients
This is a randomized, open-label, multicenter study of 1225 subjects, 12 yrs and older, with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose BF (160/4.5 µg x 2 inhalations [320/9 µg] twice daily) or fixed-dose FS (250/50 µg x 1 inhalation twice daily) for one month, after which the fixed-dose FS group continued therapy and the fixed-dose BF group was randomized 1:1 to fixed-dose BF or adjustable-dose BF (adjustable from two inhalations [320/9 µg] twice daily to two inhalations [320/9 µg] once daily or four inhalations ([640/18 µg] twice daily) for six months. There were no significant between-group differences for asthma exacerbations (primary objective), asthma symptoms, or lung function during the 7-month treatment period. The authors conclude that adjustable-dose and fixed-dose BF versus fixed-dose FS demonstrate no difference in asthma control or tolerability. Editor's comment: Most patients respond to comparable fixed-dose inhalers containing both a long-acting beta-agonist and a glucocorticosteroid. Busse WW, et al., NCBI 2008 Jun;121(6):1407-14

固定剂量及可调剂量的布地耐得/氟莫特罗(BF)压力型定量雾化吸入剂及固定剂量的氟替卡松/沙美特罗(FS)干粉吸入剂对哮喘患者的疗效比较

 该研究是随机,开放,多中心研究,共纳入1225名年龄不低于12岁的有中到重度持续性哮喘的患者。经过10-14天的治疗后,患者按2:1随机接受一个月固定剂量的BF或固定剂量的FS治疗,一个月后用固定剂量FS的患者继续维持治疗,而用固定剂量BF的患者又按1:1随机分配,在此后的六个月内或者用固定剂量的BF治疗,或者用一天两次到一天一次每次两吸至四吸的可调剂量的BF治疗。7个月的治疗期间,两组在哮喘恶化(主要终点),哮喘症状,或肺功能方面没有显著差异。作者认为可调剂量及固定剂量的BF与固定剂量的FS在哮喘控制及用药耐受性方面没有差异。编者点评多数患者对含长效beta激动剂及糖皮质激素的定量吸入剂有反应。Busse WW, et al., NCBI 2008 Jun;121(6):1407-14

2. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
Aluminium adjuvants are used in human and animal vaccines worldwide. The authors show that aluminium adjuvants activate an intracellular innate immune response system, called the Nalp3 (also known as cryopyrin, CIAS1 or NLRP3) inflammasome. Production of the pro-inflammatory cytokines, interleukin-1β and interleukin-18 by macrophages, in response to alum in vitro, require intact inflammasome signaling. Mice deficient in Nalp3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) or caspase-1 fail to mount a significant antibody response to an antigen administered with aluminium adjuvants, whereas the response to complete Freund's adjuvant remains intact. Editor's comment: Understanding how aluminium adjuvants work will help design more specific adjuvants. Eisenbarth SC, et al., Nature 2008; 453:1122.

Nalps炎性体对铝佐剂的免疫调节功能有重要作用。

 铝佐剂广泛用于人和动物疫苗。作者指出铝佐剂激活细胞内的内源性免疫应答系统,即Nalp3炎性体(也即cryopyrin,CIAS1 或 NLRP3)。体外实验中,巨噬细胞被铝制剂激活后产生前炎症因子,白介素1以及白介素18,而这个过程需要炎性体完整的信号转导。Nalp3缺陷,含凋亡起始子募集结构域的凋亡相关点状蛋白(ASC),或凋亡起始子1缺陷的小鼠经有铝佐剂的抗原刺激后无法产生显著的抗体应答,然而对完整的Freund's佐剂仍然有应答。编者点评:知道铝佐剂如何起效有助于设计更特异的佐剂。Eisenbarth SC, et al., Nature 2008; 453:1122.

3. T-cell regulation in chronic paranasal sinus disease
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a TH2-skewed eosinophilic inflammation, whereas chronic rhinosinusitis without nasal polyps (CRSsNP) represents a predominant TH1 milieu. Nasal mucosa tissue from 13 patients with CRSsNP, 16 with CRSwNP, and 10 control patients were analyzed. The authors demonstrate a decreased expression of FOXP3 in nasal polyp tissue, reflecting a deficiency or dysfunction of Treg cells, in CRSwNP. In addition, low levels of TGF-β1 protein expression and an upregulation of the transcription signals for TH1 (T-bet) and TH2 (GATA-3) subpopulations point to a defective suppression of their upregulation by Treg cells. The authors conclude by stating that a lack of Treg cells may contribute to the severe persistent TH2-skewed inflammation in CRSwNP, not present in the CRSsNP group. Editor's Comment: A lack of Treg cells may contribute to the pathogenesis of nasal polyps in CRSwNP. Van Bruaene N, et al., JACI 2008; 121:1435.

T细胞在慢性副鼻窦病中的调节作用

 伴鼻息肉的慢性鼻鼻窦炎(CRSwNP)的特征是Th2导向的嗜酸细胞炎症,然而不伴鼻息肉的慢性鼻鼻窦炎(CRSsNP)则主要是Th1的调节作用。作者分析了13名CRSsNP患者,16名CRSwNP患者以及10名对照患者的鼻粘膜组织、发现CRSwNP患者的鼻息肉组织中FOXP3的表达降低,反应了Treg细胞的缺乏或功能低下。另外,TGF-β1表达的降低及Th1和Th2亚群转录信号的上调表明Treg细胞对它们的抑制降低。作者得出结论,认为Treg细胞的缺陷使得CRSwN患者出现严重且持续的Th2导向的炎症,而这种情况在CRSsNP患者没有发生。编者点评:Treg细胞的缺陷可能引起CRSwNP患者的鼻息肉的发生。Van Bruaene N, et al., JACI 2008; 121:1435.

4. Induction and effector functions of TH17 cells
The TH17 cell, a third subset of effector T helper cells, is the subject of intense research to understand their role in immunity and disease. An excellent review of emerging data suggests that the TH17 cells have an important role in host defense against specific pathogens, some of which include Propionibacterium acnes, the Gram-negative Citrobacter rodentium, Klebsiella pneumoniae, Bacteroides spp. and Borrelia spp., the acid-fast Mycobacterium tuberculosis, and fungi such as Candida albicans. They are also potent inducers of autoimmunity and tissue inflammation. In addition, differentiation factors responsible for TH17 generation reveal an interesting reciprocal relationship with regulatory T (Treg) cells, which prevent tissue inflammation and mediate self-tolerance. Editor's comment: A fantastic review of a subject of interest to all allergists/immunologists. A must read. Bettelli E, et al., Nature 2008; 453:1051.

Th17细胞的诱导及效应功能

Th17细胞是效应性T辅助细胞的第三个亚群,很多研究致力于探讨其在免疫及疾病发生中的作用。对最新研究资料的回顾表明Th17细胞对宿主防御某些病原有重要的作用,其中包括痤疮丙酸杆菌,革兰氏阴性柠檬酸杆菌,肺炎克雷伯菌,拟杆菌及疏螺旋体,结核抗酸杆菌,白色念珠菌等真菌。Th17细胞还是自身免疫及组织炎症的潜在诱因。另外,负责Th17细胞生成的分化因子与调节性T(Treg)细胞之间有相互影响,该细胞防止组织炎症,介导自体耐受。编者点评:本文是所有变态反应科医生及免疫科医生必读的文章。Bettelli E, et al., Nature 2008; 453:1051.

5. Ciclesonide (C) improves measures of small airway involvement in asthma
16 mild-to-moderate asthma patients were randomized to receive five weeks treatment with placebo (P) vs 320 µg C once daily. Small airway parameters were assessed. Seven received P and nine C. Alveolar exhaled nitric oxide (eNO) and computed tomography (CT) measurements of expiratory lung function after methacholine (MCh) challenge decreased significantly with C vs P. It did not affect mean expiratory flow between 25 and 75% of forced vital capacity (FVC), percentage fall in FVC at the provocative dose of adenosine-5'-monophosphate or MCh causing a 20% decrease in FEV1, and single-breath nitrogen closing volume. The authors conclude that C exerts anti-inflammatory effects on the small airways. Editor's comment: Optimal treatment for some patients with asthma may require that the entire airway be treated, including the small airways. Cohen J, et al., Eur Respir J 2008; 31:1213.

环索奈德(C) 提高哮喘患者小气道功能

16名轻到中度哮喘患者随机接受5周安慰剂(P)或每天一次320ug C的治疗。评估患者的小气道功能参数。7名患者接受安慰剂治疗,9名接受C治疗。与P组相比,肺泡呼出气NO(eNO)以及用CT测得的甲基胆碱激发后的肺呼气功能在C组明显降低。用力肺活量(FVC)25%至75%时的平均呼气流速,用腺苷-5'-单磷酸或甲基胆碱激发后FEV1降低20%时的FVC降低的百分比,以及一次呼吸的氮气闭合容量不受影响。作者的结论是C对小气道有抗炎效果。编者点评:对哮喘患者的最佳治疗应该包括治疗整个气道,包括小气道。Cohen J, et al., Eur Respir J 2008; 31:1213.

6. Prevention of Herpes Zoster
The June 6, 2008 issue of the Morbidity and Mortality Weekly Report (MMWR) has an excellent article on recommendations for herpes zoster (shingles) vaccination. It is recommended for all persons aged ≥ 60 yrs who have no contraindications, including those with previous episodes of herpes zoster or those who have chronic medical conditions, regardless of their history of varicella (chickenpox) or serologically proven varicella immunity. Medical conditions include chronic renal failure, diabetes mellitus, rheumatoid arthritis, and chronic pulmonary disease. Since this is a live, attenuated vaccine, it should not be given to patients who are immunosuppressed or with immunodeficiency. Editor's comment: Pediatricians traditionally administer vaccines to children; allergists/immunologists should be the primary, or one of the specialty groups, that administer vaccines to adults. Harpaz R, et al., MMWR 2008; 57.

2008年6月6日的《死亡及致残周报》上有一篇很好的文章推荐单纯疱疹的免疫接种。建议所有年龄不低于60岁,没有禁忌症的人进行单疱免疫接种,包括既往有带状疱疹或慢性病史,不管有无水痘病史或血清学证实对疱疹免疫。疾病情况包括慢性肾功能衰竭,糖尿病,类风湿,慢性肺病。因为该疫苗是减毒活疫苗,不应该用于有免疫抑制或免疫缺陷的患者。编者点评:儿科医生给孩子注射疫苗;变态反应科医生/免疫科医生应该是给成人进行疫苗注射的主要或特殊的群体之一。Harpaz R, et al., MMWR 2008; 57.

7. Molecular Origins of Cancer; Cancer Immunology
The immune system can respond to cancer cells by either reacting against tumor-specific antigens (molecules unique to cancer cells) or against tumor-associated antigens (molecules expressed differently by cancer vs normal cells). This knowledge has stimulated the invention of many new therapeutic antibodies, cell-based treatments, and vaccines which are currently being used in clinical practice. This therapy should result in increased and improved cancer treatment and possibly, eventually, even prevent cancer. Editor's comment: This is an excellent article on tumor immunology and the immunologic reagents approved by the FDA for cancer therapy. Finn OJ, N Engl J Med 2008; 358:2704.

肿瘤的分子起源;肿瘤免疫学

免疫系统对肿瘤细胞的应答是通过对肿瘤特异性抗原(肿瘤细胞独特的分子)或肿瘤相关抗原(在肿瘤细胞上有不同于正常细胞上表达方式的分子)反应达到。这一理论促进了很多治疗性抗体、细胞水平的治疗手段以及目前正用于临床的疫苗的产生。这些方法应在很大程度上改善肿瘤的治疗,并且可能最终预防肿瘤发生。编者点评:这是一篇有关肿瘤免疫学以及FDA批准的用于肿瘤治疗的免疫性因子的很好的综诉。 Finn OJ, N Engl J Med 2008; 358:2704.

8. The ABCs of Asthma Control
The authors describe four easy steps to achieve asthma control in the ambulatory practice setting: 1) a standardized assessment of asthma symptoms using a 5-question assessment tool, the Asthma Control Test (ACT), 2) a simple mnemonic, AIRESMOG, that provides a systematic review of the comorbidities and clinical variables that contribute to uncontrolled asthma, 3) directed patient education, and 4) a schedule for ongoing care. The authors conclude that almost all patients can achieve good asthma control using this approach. The AIRESMOG Mnemonic stands for: A - Allergy and Adherence to therapy, I - Infection and Inflammation, R - Rhinitis and Rhinosinusitis, E - Exercise and Error in diagnosis, S - Smoking and pSychogenic factors, M - Medications (β-blockers, angiotensin-converting enzyme inhibitor, aspirin), O - Occupational exposures, Obesity, and Obstructive sleep apnea, G - Gastroesophageal reflux disease. Editor's comment: This AIRESMOG Mnemonic will help make asthma the most treatable of all chronic diseases. Thorsteinsdottir B, et al., Mayo Clin Prac 2008; 83:814.

哮喘控制的ABCs

作者阐述了在流动性医疗单位控制哮喘的4个简单步骤:1)用哮喘控制问卷(ACT)的5个评估问题来标准化评估患者的哮喘症状,2)用简单的记忆方法,AIRESMOG,系统回顾导致哮喘不能控制的合并情况及其它临床问题,3)患者教育,以及4)继续治疗的计划。作者的结论是几乎所有患者用此法能够获得哮喘的良好控制。AIRESMOG记忆法代表:A -过敏以及治疗依从性,I -感染及炎症,R -鼻炎及鼻窦炎,E -运动及诊断错误,S -吸烟及心理因素,M -用药(阻断剂,血管紧张素转换酶抑制剂,阿司匹林),O -职业暴露,肥胖以及阻塞性呼吸暂停,G -胃食管返留。编者点评:AIRESMOG记忆法有助于让哮喘成为所有慢性病中最好治疗的疾病。Thorsteinsdottir B, et al., Mayo Clin Prac 2008; 83:814.

9. Subspecialty differences in asthma characteristics and management
2407 patients (72%) with asthma were treated by allergists and 935 (28%) by pulmonologists in the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Patients treated by pulmonologists vs allergists were more likely to be African-American, less educated, have lower incomes, have more severe asthma, and use short-acting β-agonist and systemic corticosteroids more regularly. Although evidence of allergic disease was prevalent in both groups, those treated by allergists were more likely to be skin tested and receive immunotherapy. Those treated by pulmonologists also were more likely to report greater health care use for asthma in the previous 3 months. Editor's comment: Subspecialty differences do exist between allergists/immunologists and pulmonologists. Chen H, et al., Mayo Clin Proc 2008; 83:786.

哮喘表现及处理的专业差异

哮喘流行状况及自然病史:哮喘结局及治疗方案(TENOR)研究中,2407 (72%)名哮喘患者由变态反应科医生治疗,935(28%) 名患者由呼吸科医生治疗。呼吸科医生治疗的患者中更多的是非彝美国人,其受教育的程度低,收入低,哮喘重,更加频繁的使用短效β激动剂及全身用糖皮质激素。虽然两组患者过敏性疾病的表现都很明显,但由变态反应科医生治疗的患者更可能接受皮肤试验及免疫治疗。呼吸科治疗的患者在既往3个月因哮喘的花费更多。编者点评:专业差异的确存在于变态反应科医生及呼吸科医生之间。Chen H, et al., Mayo Clin Proc 2008; 83:786.

10. Update on mechanisms of allergen injection immunotherapy
Allergen immunotherapy is indicated for allergic rhinitis, allergic asthma and Hymenoptera hypersensitivity. Unlike pharmacotherapy, it provides long-term clinical benefits, such as long-term disease remission, prevention of new atopic sensitizations and a reduction in disease progression from rhinitis to asthma. Editor's comment: This state-of-the-art review is outstanding. James LK, Durham SR, Clin Exp Allergy 2008; 38:1074.

变应原注射免疫治疗机制的最新信息

变应原免疫治疗适用于过敏性鼻炎,过敏性哮喘及昆虫毒液过敏。不同于药物治疗,免疫治疗带来长期临床获益,如疾病的长期缓解,避免新的致敏以及减少疾病由鼻炎发展为哮喘。编者点评:这是一篇非常精彩并具有前沿性的回顾。James LK, Durham SR, Clin Exp Allergy 2008; 38:1074.

Translated by Manli Qing, PUMCH, China

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