Reviewed by Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief
1. Budesonide/formoterol (B/F) maintenance and reliever therapy:
impact on airway inflammation in asthma
1,538 patients were randomized for six months to open-label B/F maintenance
(160/4.5 µg twice daily) and B/F as needed reliever therapy. They were compared
to guideline-based practices (GBP) as managed by individual investigators.
There were no differences in time to severe exacerbation and severe asthma
exacerbation rate. However, there were fewer ER visits and hospitalizations
with B/F maintenance and reliever therapy (not statistically significant). Mean
daily inhaled corticosteroid dose, reliever use, asthma medication costs and
total annual costs per patient were all significantly lower with the B/F
maintenance and reliever therapy vs. GBP. The authors conclude that B/F
maintenance and reliever therapy vs. GBP achieves similar outcomes with
significant lower costs. Editor's comment: More data demonstrating that B/F
maintenance and reliever therapy is an effective means to control asthma.
Sears MR, et al., Eur
Respir J 2008; 31:982.
布地耐德/福莫特罗（B/F)维持及缓解治疗：对哮喘气道炎症的影响
1538名患者随机6个月，一组用B/F维持治疗 (160/4.5 µg 每日两次)并按需缓解症状，另一组患者由各自的医生按指南给予治疗，两组进行比较。哮喘恶化的时间及严重哮喘发作的情况没有显著差异。然而，B/F维持及缓解治疗组急诊及住院的次数少一些（没有统计差异）。平均每日吸入皮质激素的剂量，缓解药物的使用，哮喘治疗费用以及每名患者总的年花销在B/F治疗组显著低于GBP组。作者认为B/F维持及缓解治疗与GBP相比临床结局相似但治疗费用要低得多。编者点评：更多数据显示B/F维持及缓解治疗是控制哮喘的有效措施。Sears
MR, et al., Eur
Respir J 2008; 31:982
2. Impaired TH17 cell differentiation in subjects
with autosomal dominant hyper-IgE syndrome (HIES, 'Job's syndrome')
TH17 cells, a subset of helper T cells, are critical to clear fungal
and extracellular bacterial infections. These authors show that interleukin
(IL)-17 production ex vivo by T cells from HIES individuals fails to
produce IL-17, but not IL-2, tumour-necrosis factor or interferon-γ, on
mitogenic stimulation with staphylococcal enterotoxin B or on antigenic
stimulation with Candida albicans or streptokinase. Purified naďve T cells
did not differentiate into IL-17 producing (T H17) T helper cells in
vitro and had lower expression of retinoid-related orphan receptor
(ROR)-γt, consistent with a crucial role for STAT3 signaling in the
generation of T H17 cells. Mutations in HIES patients have been
identified in stat3, the gene encoding STAT3 (signal transducer and
activator of transcription 3), presumed to underlie HIES. These data suggest
that a lack of TH17 cells in HIES is a mechanism for recurrent
infections. Editor's Comment: Improving IL-17 production may help patients
with HIES. Milner JD, et al., Nature 2008; 452:773.
常染色体显性高IgE综合征患者Th17细胞分化障碍（HIES,'Job'综合征）
TH17细胞，是T辅助细胞的一个亚群，对于清除真菌及细胞外细菌感染很关键。用葡萄球菌肠毒素B作为丝裂原刺激后，或用白色念珠菌或链激酶行抗原刺激后，HIES患者的T细胞在体外不能生成IL-17，但IL-2，肿瘤坏死因子或γ-干扰素的产生不受影响。体外纯化的纯真T细胞没有分化为产IL-17的T辅助细胞（TH17），孤儿核受体（ROR)- γt的表达也降低，这些现象支持STAT3信号转导在T H17 细胞生成中起到关键作用。HIES患者Stat3基因存在突变，该基因编码STAT3（信号转导及转录3激活子），目前认为后者是HIES的病因之一。这些资料提示HIES患者TH17细胞的缺乏是其发生反复感染的机制之一。编者点评：改善IL-17生成对HIES的患者有利。Milner JD, et al., Nature 2008; 452:773.
3. Allergens are distributed into few protein families and
possess a restricted number of biochemical functions
Allergen data from the Allergome database and protein family definitions from
the Pfam database were merged into a databased, AllFam, accessible on the
Internet at http://www.meduniwien.ac.at/allergens/allfam/. 707 allergens were
classified by sequence into 134 AllFam families containing 184 Pfam domains or
2% of 9318 Pfam families. These data indicate a similarity in protein structure
in all allergens. The small number of protein families that contain allergens,
and the narrow functional distribution of most allergens, confirm the existence
of yet unknown factors that render these proteins allergenic. Editor's
comment: Brilliant research bringing together 2 databases to show that most
allergenic structures are contained in relatively few protein families. Radauer C,
et al., J Allergy Clin Immunol 2008; 121:847.
4. Recapitulation of IVIG anti-inflammatory activity with a
recombinant IgG Fc
The use of monomeric immunoglobulin G (IgG) confers anti-inflammatory activity
for a variety of autoimmune diseases. This article demonstrates that the
anti-inflammatory activity of IgG is dependent on sialylation of the N-linked
glycan of the IgG Fc fragment. The authors identified the precise glycan
requirements for this anti-inflammatory activity, allowing them to engineer an
appropriate IgG1 Fc fragment, thus generating a fully recombinant, sialylated
IgG1 Fc with greater enhanced potency, thereby precisely defining the
biological active component of IVIG. They conclude that it may be possible to
develop an IVIG replacement with improved activity and availability. Editor's
comment: It would be ideal to capture the anti-inflammatory effect of IVIG
without the need for human donors. Anthony RM, et al., Science 2008; 320:373.
重组IgG Fc片断具有IVIG的抗炎作用
IgG单体在很多自身免疫性疾病中起到了抗炎作用。本文发现IgG的抗炎活性依赖于IgGFc片断N-端糖基的唾液酸化。作者发现抗炎活性所需的明确的糖基位点，从而可以制备合适的IgG1Fc片断，制造一个完全重组的，更加高效的，唾液酸化的IgG1Fc片断，精确的诠释IVIG的生物活性。他们认为有可能开发一种活性更高且更易获得的IVIG替代品。编者点评：理想的情况是不用人类供体而获得IVIG的抗炎效果。Anthony RM, et al., Science 2008; 320:373
5. Nonsurgical management of obesity (O) in adults
O is a major risk factor for asthma, particularly in women. This article
reviews the strategies involved in the non-surgical management of O. Assessing
co-existing conditions, such as hypertension, glucose intolerance,
dyslipidemia, and obstructive sleep apnea is important, and a reduction as low
as 5-10% of body weight may be sufficient to favorably modify a variety of
outcomes for these diseases. Lifestyle approaches include low-fat diets,
low-glycemic-index diets, high-protein diets, and specific commercialized diets.
The most interesting section of the article discusses drugs prescribed for
weight loss, none of which are extremely effective vs. placebo. These
medications include diethylpropion, orlistat, phentermine, sibutramine, and
rimonabant. Not only is weight reduction difficult, maintaining it is equally
difficult. Eating a low-fat diet, frequent self-monitoring of weight and food
intake, high levels of physical activity, long-term patient-physician contact,
and the careful use of medications are essential measures for successful
outcomes. Editor's comment: This is a wonderful discussion outlining the
treatment of obesity, a risk factor for severe asthma. Eckel RH, N
Engl J Med 2008; 358:1941.
成人肥胖的非手术治疗
肥胖是哮喘尤其是女性哮喘的主要危险因素。本文综述了非手术治疗肥胖的方法。评价如高血压，糖耐量降低，血脂异常，以及阻塞性呼吸暂停等并发症非常重要，体重减轻5-10%足以改善这些疾病的预后。生活方式的改进包括低脂饮食，低糖饮食，高蛋白饮食，以及特殊的商业化饮食。文章最吸引人的是它讨论了减肥药物，认为这些药物与安慰剂相比没有显著效果，这些药包括二乙胺苯丙酮，奥利司他，苯丁胺，西布曲明以及利莫那班。不仅减肥很困难，保持体重也同样困难。低脂饮食，频繁的自我监控体重及进食量，大量的体育活动，长期的患者医生交流，以及认真用药对于减肥成功至关重要。编者点评：肥胖是严重哮喘的一个危险因素，而本文针对肥胖治疗进行了非常棒的讨论。
6. Severe atopic dermatitis (AD) is associated with a high
burden of environmental Staphylococcus aureus (S. aureus)
These authors quantified the S. aureus burden in homes of patients with
AD of varying severities and normal subjects. Dust was collected from their
bed, bedroom floor, and home vacuum cleaner bag and the DNA extracted and
quantified for the S. aureus-specific femB gene using
quantitative real-time PCR. In general, participants with severe AD had
significantly more S. aureus DNA in their bed dust than those with
moderate, mild or no AD. Similar patterns were observed for dust from the
bedroom floors and vacuum bags. The authors conclude that the high levels of S.
aureus could contribute to disease severity and persistence in AD patients.
Editor's comment: Patients with AD are colonized with S. aureus.
Higher levels of this same organism are found in homes of AD subjects and
correlate with its severity. Leung AD, et al., Clin Exp Allergy 2008; 38:789.
严重的特应性皮炎与环境中大量的葡萄球菌有关
作者对不同病情AD患者家里及正常人家里的葡萄球菌进行定量测定。收集床上，卧室地板，家庭收尘袋的尘土，提取DNA，用实时定量PCR法测定葡萄球菌特异性femB基因。总的来说，严重AD患者比起中轻度AD患者或正常人而言，其床上尘土中葡萄球菌DNA要多得多。卧室地板及收尘袋的尘土也有类似的情况。作者得出结论，大量的葡萄球菌会使AD患者病情加重且迁延不断。编者点评：AD患者有葡萄球菌的定植。AD患者家中存在更多葡萄球菌，且细菌量与疾病的严重性相关。Leung AD, et al., Clin Exp Allergy 2008; 38:789.
7. Safety of long-acting β-agonists in stable COPD (A
systematic review)
This meta-analysis of 27 randomized clinical trials (≥ one month in
duration) compares LABAs with placebo (P) or anticholinergics in stable poorly
reversible and reversible COPD. LABAs reduced severe exacerbations vs. placebo
(RR, 0.78; 95% confidence interval [CI], 0.67 to 0.91). There was no significant
difference between LABA and P groups for respiratory deaths. LABAs used with
inhaled corticosteroids (ICS) reduced the risk of respiratory deaths compared
to LABAs alone (RR, 0.35; 95% CI, 0.14 to 0.93) and significantly improved
airflow limitation measures, health-related quality-of-life and decreased the
use of rescue medication. Tiotropium bromide vs. LABAs decreased the incidence
of severe COPD exacerbations (RR, 0.52; 95% CI, 0.31 to 0.87). There is no
increased risk of respiratory deaths associated with the use of LABAs. Editor's
comment: Tiotropium bromide is first-line therapy for stable COPD followed by a
LABA preferably used with an ICS. Rodrigo GJ, et al., Chest 2008; 133:1079. (editorial: Sears,
p. 1057).
长效β受体激动剂在COPD稳定期的安全性（系统复习）
这项荟萃分析纳入了27项为期不短于1个月的随机临床试验，比较LABA与安慰剂或抗胆碱能药物对稳定的难逆转及可逆转COPD的治疗效果。LABAs与安慰剂相比，降低了COPD的严重发作（RR,0.78，95%置信区间0.67-0.91)。与安慰剂相比，LABA的使用明显降低了呼吸衰竭所致的死亡。LABA与吸入糖皮质激素合用与单用LABA相比，前者降低了呼吸衰竭导致的死亡（RR，0.35;
95% 置信区间, 0.14 to 0.93），显著改善了气流受限的情况，改善了生活质量，降低了急救药物的使用。噻托嗅铵与LABA相比，降低了严重COPD恶化的发生率(RR, 0.52;
95% CI, 0.31 to 0.87)。使用LABA并没有增加呼吸衰竭造成的死亡。编者点评：噻托嗅铵是稳定期COPD的一线治疗，其次是LABA联合ICS治疗。
8. Issues in the diagnosis of α1-antitrypsin
deficiency (AATD)
This is a thorough review of AATD, an under-recognized and underdiagnosed
worldwide problem. The authors outline the diagnostic challenges, guidelines to
confirm the diagnosis, and a call to physicians to have a high index of
suspicion for this deficiency. Those at highest risk are those who have early
signs or symptoms of emphysema, unexplained liver disease, necrotizing
panniculitis, anti-proteinase 3-positive vasculitis, bronchiectasis, or a
family history of any of these diseases. The method to diagnose this disease is
outlined in an algorithm. The authors conclude with treatment options which
include α1proteinase inhibitor therapy. Editor's comment:
AATD is a common problem, with a similar prevalence to cystic fibrosis, but
remains greatly underdiagnosed and treated. Rachelefsky G, Hogarth K, J Allergy Clin Immunol 2008; 121: 833.
α1抗胰蛋白酶缺陷(AATD)的诊断
本文对AATD，一个尚未得到充分认识和诊断的疾病进行了全面的复习。作者综述了诊断方面的困难，确诊的规范，并呼吁医生在出诊时想到这个疾病的可能。有早期肺气肿症状和体征的人、不明原因的肝脏疾病、坏死性脂膜炎、抗蛋白酶3阳性血管炎，支气管扩展，或有上诉任何疾病家族史的患者都是是该病的高危人群。该病的诊断方法用图表显示出来。作者最后提到了包括α1蛋白酶抑制剂在内的治疗方法。编者点评：AATD是一常见疾病，其患病率与囊性纤维化相似，但尚未得到充分的诊断和治疗。Rachelefsky G,
Hogarth K, J Allergy Clin Immunol 2008; 121: 833.
9. Nasal and sinus endoscopy for medical management of resistant
rhinosinusitis, including postsurgical patients
This paper outlines the utility of performing nasal endoscopy, practiced by
some allergists since 1980. However, for reasons unexplained, allergists, in
general, have not embraced its use. It discusses the history of nasal endoscopy
and outlines the advantages of flexible vs. the rigid endoscope. There are few
safety issues for its routine use. The article explains how endoscopy can
assist the physician to understand and follow patients with a variety of nasal
problems, particularly, chronic rhinosinusitis. Editor's comment: Nasal
endoscopy is not only used to diagnose and assess nasal pharyngeal problems but
also oral and laryngeal problems. It should be utilized by allergists
throughout the world. Tichenor WS, et al., J Allergy Clin Immunol 2008; 121:917.
鼻及鼻窦内窥镜对难治性鼻鼻窦炎的治疗，包括对术后患者的治疗。
本文综述了1980年以来一些变态反应科医生对鼻内窥镜的使用。然而，出于未知的原因，变态反应科医生尚未普遍接受鼻内窥镜的使用。文章讨论了鼻内窥镜的历史，综述了软内镜及硬内镜的优点。常规使用鼻内窥镜很少出现安全问题。文章阐述了医生如何用内窥镜帮助自己认识患者的鼻部疾病并且进行随诊，尤其是对于慢性鼻窦炎的患者。编者点评：鼻内窥镜不仅用于诊断和评估鼻咽疾病，也可用于口咽疾病，应该得到全球变态反应科医生的使用。Tichenor WS, et al.,
J Allergy Clin Immunol 2008; 121:917.
10. Irritable Bowel Syndrome (IBS)
IBS has a worldwide prevalence of 10 - 15%. It is always included in
differential diagnosis of most chronic GI problems, and, in particular, in the
differential diagnosis by many physicians and patients of food allergy. This is
an excellent review of IBS and its differential diagnosis, which includes celiac
sprue, microscopic and collagenous colitis and atypical Crohn's disease, and
chronic constipation. An algorithm of the differential diagnosis is included as
well as an extensive list of medications to treat IBS. Editor's Comment:
Patients with IBS frequently present to the allergist because they wonder
whether or not they are allergic to certain foods. IBS is always in the
differential. Mayer EA, N
Engl J Med 2008; 358:1692.
肠易激综合征（IBS)
全球IBS的患病率达10-15%。多数慢性胃肠道疾病要与IBS相鉴别，尤其要鉴别于食物过敏。本文是有关IBS及其鉴别诊断的一篇很好的综述，后者包括乳糜泄，显微性及胶原性结肠炎，非典型克罗恩病，以及慢性便秘。文章包括了IBS鉴别诊断的图解，以及IBS药物治疗的内容。编者点评：IBS的患者因为想了解自己是否对某些食物过敏而经常到变态反应科就诊。变态反应科医生在鉴别诊断时常常要考虑到IBS。Mayer EA, N
Engl J Med 2008; 358:1692.
11. Screening for osteoporosis in men: A systematic review for
an American College of Physicians guideline
This study identifies men at risk for low bone mineral density (BMD) and fracture.
The most important risk factors for low BMD-mediated osteoporotic fracture in
men without a known diagnosis of osteoporosis or fracture are increased age
(>70 years) and low body weight (body mass index <20 to 25 kg/m2) or weight < approximately 70 kg. Additional risk factors include a variety of health conditions and medications, particularly, weight loss, physical inactivity, prolonged corticosteroid use,
previous osteoporotic fracture and androgen deprivation therapy. Cigarette
smoking is associated with lower BMD, but there is less evidence in men to
determine its association with fracture. Editor's comment: Osteoporosis is a
risk factor for patients with chronic obstructive lung disease (COPD) as well
as those treated with glucocorticosteroids. Appropriate screening of men is as
equally important as is screening of women for this disease. Liu H, et al.,
Annals
Int Med 2008;148:685.
男性骨质疏松的筛查：为美国医师学院所做的系统性复习
该项研究旨在发现有低骨密度及骨折危险的男性。高龄、低体重（体重指数<20 到25 kg/m2）或体重低于70kg左右，是骨密度介导的骨质疏松性骨折最重要的危险因素。其它危险因素包括一些疾病及药物，尤其是体重减轻，不活动，长期用糖皮质激素，以前有骨质疏松导致的骨折以及消耗雄激素的治疗。吸烟与体重指数低有关，但其与男性骨折的关系证据还不足。编者点评：骨质疏松是慢性阻塞性肺病患者及激素治疗患者的危险因素。适当筛查男性骨质疏松和筛查女性骨质疏松同样重要。Liu H, et al., Annals Int Med 2008;148:685.
