WAO Email News and Notes

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.

ブデソニドとフォルモテロール合剤の一日２回維持＋増悪時使用の喘息コントロールに関する効果を現在のガイドラインに記載された標準治療法と比較して検討した。その結果、ブデソニドとフォルモテロール合剤はガイドライン記載の標準治療法と比較し同等に有効で、薬剤使用量は少なく、コストも安く済んだ。

2. Impaired T_H17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome (HIES, 'Job's syndrome')
T_H17 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 naïve 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 T_H17 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.

TH17細胞は新たに発見されたヘルパーT細胞サブセットであり、真菌や細胞外の（＝細胞内はTH1細胞が対応）細菌感染免疫に重要な役割を演じている。高IgE症候群は乳児期から始まる高IgE血症および難治性湿疹や皮膚や肺などの黄色ブドウ球菌による反復感染によって特徴づけれらる免疫不全症候群である。著者らは高IgE症候群の少なくとも一部の患者は、TH17細胞の分化に必須なIL-6の情報を伝える転写因子Stat3の変異があることを見いだした。TH17細胞によるTH2細胞の抑制解除により高IgE血症が生じ、Stat3の遮断により強い炎症を伴わない冷膿瘍などの症状が生じるのであろう。

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.

全てのアレルゲンの蛋白質構造のデータを分析したところ、それぞれ特有の生化学的な働きをもつ２，３の蛋白質ファミリーに分類されることがわかった。

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.

免疫グロブリン大量静注IVIG療法は多くの炎症性疾患に有効である。メカニズムは永らく不明であったが、著者らは、IgGの抗炎症効果はFc部分の糖鎖のシアル化の程度に依存することをつきとめた。そして、マウスのモデルにおいて、シアル化された遺伝子組み換えのIgG Fc分子は強い抗炎症効果をもつことを証明した。

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.

肥満は特に女性において喘息発症の主要なリスクファクターである。これはN Engl J Medに最近掲載された非外科的手法による肥満対策に関するClinical Practiceシリーズの論文である。薬物療法などについても記載されており興味深い。

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.

アトピー性皮膚炎患者の家庭では、寝室の床や浮遊塵中の黄色ブドウ球菌のレベルが高かった。

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).

長時間作用型β2刺激薬LABAの慢性閉塞性肺疾患COPDに対する効果に関するシステマティックレビューである。COPDの治療に関しては抗コリン薬Tiotropium bromideが第一選択でLABAはその次に位置する。LABAの使用は吸入ステロイドとの併用が望ましい。

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 α₁ proteinase 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-antitrypsin欠損症は特に我が国では稀な疾患であるが、重篤な気管支拡張症などの症状をひきおこす。この総説においては米国でさえも、診断や治療が十分に行われてないことを紹介している。

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.

鼻腔や副鼻腔の内視鏡検査は有用であり、アレルギー専門医は修得すべきとしている。

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.

過敏性腸症候群についてN Engl J Medに最近掲載されたClinical Practiceシリーズの論文である。アレルギー専門医は鑑別診断として常に考慮しておく必要がある。

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.

男性の骨粗鬆症に関するシステマティックレビューである。COPDやステロイド使用者は注意すべきである。

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Allergy Book Review

今月の本の紹介はLiebermanのAllergic Diseases 第３版である。これからアレルギー専門医を目指す医師を対象にしたポケットガイドとして相応しい。

Allergic Diseases: Diagnosis and Treatment, 3rd Ed.

Author: Phil Lieberman

ISBN: 9781588296030

Available from: Humana Press List Price: $99.00 USD

Reviewer: Josh Phillips, MD Division of Allergy & Immunology University of South Florida College of Medicine

Description

Allergic Diseases: Diagnosis and Treatment in its third edition provides a thorough and comprehensive review of the pathophysiology, diagnosis, and treatment of common allergic diseases. Emphasis is placed on the allergic history and physical examination with further attention to appropriate diagnostic tests and information on when to refer to an allergist/immunologist. Each of the more than 40 contributors is an expert.

Purpose

The textbook is designed as a guide to the general approach and management of allergic diseases.

Audience

As noted in the preface, this textbook is intended for use by primary care physicians but also would be an excellent book for a new trainee in the subspecialty of allergy and immunology.

Content / Features

Chapters are presented as review articles, with abstract-style summaries and medical subject heading (MeSH) keywords. Introductory chapters address the pathophysiology of allergic diseases and the approach to the allergic patient. Subsequent chapters focus on individual allergic problems such as anaphylaxis, sinusitis, allergic rhinitis and many others. There are also chapters dedicated to specific therapies such as corticosteroids, monoclonal anti-IgE, antihistamines, and leukotrienes, as well as a chapter dedicated to the workup of recurrent respiratory tract infections in children.

Assessment / Comparison

At 484 pages, this textbook is more of a comprehensive resource than a "pocket" guide. Individual points are not specifically referenced; rather there is a list of suggested reading at the end of each chapter. Additionally, illustrations and photographs rather than being in color are in black & white. A few minor spelling errors are noted. Despite these minor problems, this text is a highly detailed and practical guide for all physicians but particularly, for primary care physicians.

Find more allergy book reviews on the WAO Website here.