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September Medical Journal Review(医学雑誌レビュー)
WAO Now: What's New in the World of WAO(最新ニュース)
And In Other News . . .(その他のニュース)

September World Medical Journal Review(医学雑誌レビュー)

Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, reviewed premier September medical journal articles for practicing allergists. 南フロリダ大学 Richard F. Lockey助教授による8月の医学雑誌に掲載されたアレルギー関連の文献紹介である。

1. ANTI-INFLAMMATORY ACTIVITY OF IMMUNOGLOBULIN G (IgG) RESULTING FROM Fc SIALYLATION
IgG is both pro- and anti-inflammatory via engagement of its Fc fragment (Fc) with distinct Fcγ receptors (FcγRs). Some Fc-FcγR interactions generate pro-inflammatory effects of immune complexes and cytotoxic antibodies, however, in contrast, therapeutic IVIG and its Fc fragments are anti-inflammatory. These authors demonstrate that IgG acquires anti-inflammatory properties upon Fc sialylation, which is reduced upon the induction of an antigen-specific immune response. This differential sialylation may provide a switch from innate anti-inflammatory activity in the steady state to generating adaptive pro-inflammatory effects upon antigenic challenge. This study suggests that another type of difference between antibody molecules, determined by sequences of attached oligosaccharides, may be crucial for antibody function. Editor’s comment: The sugar moieties attached to the Fc fragment of IgG alter its activity. This knowledge may be useful in designing therapies for IVIG. This is exciting and innovative research and must reading for all allergists/immunologists. Kaneko Y, et al. Science 2006; 313: 670. Editorial by Burton DR, Dwek RA, p. 627.

免疫グロブリンIgGは好中球やマクロファージを介して炎症反応を引き起こす。一方、IgGの大量静注療法は川崎病やリウマチ性疾患に対して著明な抗炎症作用を有し、しばしば使用されている。著者らは、シアル酸が結合していないIgGは炎症細胞を刺激し、疾患モデルマウスにおいて強い炎症反応をひきおこすのに対し、糖鎖にシアル酸が多く結合しているIgGは好中球やマクロファージに対する結合力が弱く、大量静注により疾患モデルマウスの炎症を抑制することを見いだした。編集者注:糖鎖を修飾することにより理想的な抗炎症治療薬としてのIgGを作成できる。訳者注:インフルエンザなどのウイルス感染ではノイラミニダーゼが遊離され、ウイルスの感染の拡大をひきおこすことが知られており、事実、ノイラミニダーゼ阻害薬はインフルエンザに対し著効を示している。本論文によれば、ノイラミニダーゼはIgGのシアル酸結合を切断し、IgGの炎症作用を増強する。したがって、IgG大量静注療法にノイラミニダーゼ阻害薬を併用するとさらに有効なのではないだろうか?

2. MAST CELLS (MC's) CAN ENHANCE RESISTANCE TO SNAKE AND HONEYBEE VENOMS
It has been proposed that activation of MC's by snake or insect venoms can contribute to increased morbidity and mortality. However, the authors demonstrate that MC's can significantly reduce snake-venom-induced pathology in mice, at least in part by releasing carboxypeptidase A and possibly other proteases, which degrade venom components. MC's also significantly reduce the morbidity and mortality induced by honeybee venom. Editor’s comment: MC's mediators can be beneficial or detrimental to the host. Metz M, et al. Science 2006; 313: 526.

マスト細胞のもつ顆粒蛋白の一つカルボキシペプチダーゼAはヘビ毒やハチ毒を変性させること、マスト細胞欠損マウスではこのような作用が低下していることがわかった。編集者注:マスト細胞は生体にとって有害なアレルギーをひきおこすのみならず、有利に働く場合もある。訳者注:マスト細胞の生体防御機能については近年多く報告されているが、この研究によりまた新たな側面がみつかったといえる。

3. EFFECTS OF A LEUKOTRIENE RECEPTOR ANTAGONIST (LTRA) ON EXHALED LEUKOTRIENE E4 (LTE4) AND PROSTANOIDS IN CHILDREN WITH ASTHMA
This open-label study with oral montelukast (5 mg once d for 4 wk) in 17 atopic children with asthma and 16 atopic children without asthma was designed to study the effects of LTRA on exhaled LTE4 and prostanoids in children with asthma vs controls. Pretreatment exhaled LTE4 (P < .0001) and 8-isoprostane (P < .0001) values were higher in asthmatics than those without asthma. Montelukast reduced exhaled LTE4 by 33% (P < .001) in patients with asthma and the reduction was correlated with pretreatment LTE4 values (r = -0.90; P = .0001). Montelukast had no effect on exhaled LTE4 in atopic children without asthma or on exhaled 8-isoprostane and PGE2 in either group. Nitric oxide (NO) concentrations were reduced by 27% after montelukast in the asthma group. Editor’s comment: Is this a method to identify patients who are most responsive to LTRAs? Perhaps! Montuschi P, et al. J Allergy Clin Immunol 2006; 118: 347.

アレルギー性喘息の小児とアレルギーはあるが喘息のない小児を対象として、ロイコトリエン拮抗薬モンテルカスト(LTRA)の呼気中の窒素酸化物NO(呼気で測定可能な最も鋭敏な炎症マーカー)やロイコトリエンLTE4、プロスタグランディンなどの濃度などを測定した。その結果喘息患児では対照の非喘息アレルギー児に比し、これらのメディエーターが増加しており、LTRA使用によりプロスタグランディンには影響を与えずNOおよびLTE4が減少した。しかし、喘息のないアレルギー児の呼気中では変化を認めなかった。編集者注;LTRAの効果判定に使えるかもしれない。

4. DURATION OF AIRBORNE FEL d 1 REDUCTION AFTER CAT WASHING
Twelve adult female American domestic short-hair and medium-hair cats were washed by the immersion technique (immersed in tap water to the level of their heads, pelts massaged for three minutes, followed by a three-minute immersion in fresh water and then towel dried) to determine duration of airborne Fel d 1 reduction after cat washing. These washings did result in a 4- to 5-fold decrease in Fel d 1 collection at three hours, with a return to baseline within one day after washing. The authors conclude that washings do result in significant Fel d 1 reduction, but the reductions are short lived. It is unlikely that the average cat owner will experience meaningful improvement in allergic symptoms with this environmental control method. Editor’s comment: Cat allergic individuals should eliminate cats from their homes. Nageotte C, et al. J Allergy Clin Immunol 2006; 118: 521.

猫を一定の方法で洗うことでネコアレルゲンであるFel d 1のレベルが4分の1から5分の1に低下することが示されている。しかし、ネコアレルギーの患者には有効な方法ではないと思われる。編集者注:ネコアレルギー患者は猫を遠ざけるべきである。

5. NO EFFECTS OF PROBIOTICS ON ATOPIC DERMATITIS (AD) IN INFANCY: A RANDOMIZED PLACEBO-CONTROLLED TRIAL
In this randomized, double-blind, placebo-controlled study, the clinical and immunological effects of two probiotics strains of bacteria on AD in infancy were assessed. After a 4-6 week baseline and double-blind, placebo-controlled challenge to diagnose cow’s milk allergy (CMA), and a 4-6 week baseline, infants less than five months old with AD received either a hydrolysed, whey-based formula as placebo (n = 17) or hydrolysed, whey-based formula supplemented either with Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for three months. Only four infants were diagnosed with CMA and no clinical or immunologic effects of probiotic bacteria were evident. Editor’s comment: The controversy continues about probiotics in the treatment of AD. Brouwer ML, et al. Clin Exp Allergy 2006; 36: 899.

乳酸菌などのプロバイオティクスの乳児アトピー性皮膚炎に対する効果がランダム化、ダブルブラインド化された対照比較試験で実施された。その結果、有効性は認めなかった。訳者注:乳児期早期のプロバイオティクス使用はアレルギー発症やアトピー性皮膚炎に有効性を認めたという報告が多いが、今回の報告との相違点に関して科学的に解析することが必要である。

6. RELATIVE CORTICOSTEROID INSENSITIVITY OF PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC's) IN SEVERE ASTHMA
PBMC's from patients with severe asthma (n = 16), as defined by the American Thoracic Society, were compared to nonsevere asthma (n = 19) and normal volunteers (n = 10) to determine the suppression of lipopolysaccharide (LPS)-induced cytokine release by dexamethasone (D). Baseline spontaneous or stimulated release of cytokines was similar among all groups, however, LPS-induced release of IL-1β (P < 0.03), IL-8 (P < 0.03), and macrophage inflammatory protein 1α (MIP-1α) (P < 0.003) was less suppressed by D in severe asthma. This phenomenon was associated with a reduction in nuclear histone deacetylase activity (P < 0.01), an important determinant of the inflammatory response and of corticosteroid responsiveness that parallels impaired corticosteroids sensitivity (CS). Editor’s comment: Diminished CS in severe asthma affects the PBMC's. Hew M, et al. Am J Respir Crit Care Med 2006; 174: 134.

重症喘息患者16名、非重症喘息患者19名、正常対照10名についてLPS刺激による単球からのサイトカイン(IL-1beta, IL-8, MIP-1alpha)遊離およびステロイド(デキサメサゾン)による抑制効果を比較した。その結果、重症喘息患者単球ではステロイドによるサイトカイン産生抑制効果が有意に低下していた。しかも、これらの患者由来単球ではヒストン脱アセチル化酵素(HDAC)活性が低下していた。訳者注:HDAC活性が低下すると、核内のヒストン蛋白はアセチル化され、ヒストン蛋白と結合して閉じていた遺伝子の転写活性が上昇し、その結果炎症性サイトカインの転写が増加すること、ステロイド及び低濃度のテオフィリンは気道平滑筋等の細胞のHDACを増加させ炎症を抑制することが著者(Peter Barnes)らのグループから報告されている。この報告では、喘息患者単球では炎症性サイトカインの分泌は正常と同等であるが、ステロイドに対する感受性だけが低下していると述べている。非常に興味深い報告である。しかしHDAC活性の変化は癌抑制遺伝子など多くの遺伝子転写に影響するはずであるが、ステロイドの感受性だけに影響するのであろうか。また、それは先天的な遺伝子変異によるのか、それともエピジェネティックな影響であろうか。もし、後者なら造血幹細胞から単球を経て、マクロファージや樹状細胞に至るどの分化段階でHDAC活性の変化が生じるのであろうか。また、それはステロイドや炎症性サイトカイン等により影響を受けるのか等々、解決すべき問題点は多い。

7. SYSTEMIC CORTICOSTEROID (SC) THERAPY FOR ACUTE ASTHMA EXACERBATIONS
This is a nice summary of the management of acute asthma with systemic CS. The authors call for the early use of an IV, intramuscular or oral CS within one hour of arrival in the emergency department, shown to reduce admission rates by up to 60%. They state that there is no clear evidence to support any one route of SC administration over another and that the doses in a nine-study meta-analysis demonstrate that doses of >80mg/d methylprednisolone or its equivalent offer no therapeutic advantage in the initial management of acute severe asthma. Editor’s comment: A great review article on the use of SC for severe asthma exacerbations. Fiel SB, Vincken W. J of Asthma 2006; 43: 321.

急性喘息発作時におけるステロイドの全身投与に関する作用、副作用をまとめた総説である。編集者注:大変優れた総説である。

8. CYTOKINES OR THEIR ANTAGONISTS FOR THE TREATAMENT OF ASTHMA
This review is about various cytokines or their antagonists as possible treatments for asthma. The use of human monoclonal antibodies against IL-5 and a recombinant human soluble IL-4 receptor have not proven successful in patients with persistent asthma. Neither has administration of the potential anti-inflammatory cytokines IL-12 and interferon-γ. Tumor necrosis factor (TNF)-α is important in the persistence of inflammation and in patients with severe oral steroid-dependent asthma. Soluble TNF-α receptor (anti-TNF-α) has demonstrated promising results. Editor’s comment: The magic cytokine or its antagonists are yet to be discovered, however, anti-TNF-α shows promise for severe asthma. O’Byrne PM. Chest 2006; 130: 244

喘息に対するサイトカインおよび抗サイトカイン療法に関する総説である。編集者注:抗TNFαのみが有望であると思われる。

9. OBESITY AND ASTHMA
Obesity leads to metabolic and cardiovascular diseases and may increase asthma risks. Animal experiments suggest that the airway inflammation response is enhanced by both endogenous and exogenous leptin, which is increased in obese humans and is also a central mediator of inflammation in obesity. Cross-sectional and prospective cohort studies in humans show a slight increased incidence and prevalence of asthma in obese subjects, however, body mass does not appear to be a significant modifier of severity. Editor’s comment: Obesity seems to increase the incidence and prevalence of asthma. Beuther DA et al. Am J Respir Crit Care Med 2006; 174: 112.

最近、肥満で増加するレプチンが炎症を惹起するという動物実験、及び種々の疫学調査から肥満は喘息の増悪因子であることが示唆されている。著者らは、肥満は喘息の発症率を若干高めることが確認されたが、体重そのものは影響しないとしている。

10. HERBAL MEDICINES FOR THE TREATMENT OF COPD: A SYSTEMATIC REVIEW
This is a review of 14 randomized clinical trials of 14 different herbal medicines.The conclusions are that the effectiveness of herbal medications to treat COPD is not established beyond reasonable doubt and that evidence from randomized clinical trials is scarce and often methodologically weak. Editor’s comment: The combination of long acting beta agonists and ipatropium bromide is a treatment of choice for COPD. Guo R, et al. Eur Respir J 2006; 28: 330.

生薬の慢性閉塞性肺疾患COPDに対する有効性についてまとめた総説論文である。結論として、ほとんどエビデンスがないそうである。編集者注:COPDにはLABAと抗コリン薬吸入ipratropium bromide がよい。


WAO Now: What's New in the World of WAO (最新ニュース)

WAO-JSA International Session

WAOと日本アレルギー学会における共同シンポジウムが日本アレルギー学会第56回総会において11月2日に開催されます。日本アレルギー学会会員の皆様、是非、参加して下さい。

The World Allergy Organization and the Japanese Society of Allergology will present a joint session titled 'New trends in treatment of allergic disease' during the Japanese Society of Allergology’s 56th Annual Meeting.

Thursday, 2 November 2006
9:00 a.m. ‑ 11:30 a.m.
Tokyo International Forum

Chairpersons: Michael A. Kaliner and Takemasa Nakagawa

  • "New Trends in the Treatment of Asthma, Rhinitis and Sinusitis"
    Michael A.Kaliner
  • "Unmet needs and lack of response in the treatment of allergy and asthma: From noncompliance to pharmacogenetics"
    Lanny J.Rosenwasser
  • "From ARIA guidelines to InterAirways"
    Jean Bousquet


KAAACI-WAO Joint Congress 2006 & the 9th WPAS

The Korean Academy of Asthma, Allergy and Clinical Immunology and World Allergy Organization Joint Congress 2006 and the 9th West Pacific Allergy Symposium will take place in Seoul, Korea, 3-5 November 2006, at the Grand Hilton Seoul.

WAO is excited to partner with KAAACI and WPAS and pleased that many members of the WAO Board of Directors will participate as invited speakers at the congress. The scientific program highlights some of the most significant developments in clinical and basic research in allergy and clinical immunology, and Seoul will be an exciting new venue for up and coming scientists to share these cutting-edge technologies and ideas.

WAO Board Presentations:

  • "Real life classification of allergic rhinitis"
    G. Walter Canonica
  • "Allergic rhinitis: A disease remodeling the upper airways?"
    Paul B. Van Cauwenberge
  • "Ocular allergy: Implications for the clinical immunologists"
    Connie H. Katelaris
  • "Global management of rhinitis, sinusitis and asthma: What's new?"
    Michael A. Kaliner
  • "Positioning of anti-IgE antibody in asthma"
    Bob Q. Lanier
  • "The impact of allergic rhinits on bronchial asthma"
    Ruby Pawankar
  • "Functional assessment of pathogenic IgG subclasses in chronic autoimmune urticaria"
    Allen P. Kaplan
  • "New aspects of antihistamines in allergic skin disease"
    F. Estelle R. Simons
  • "Inhibition of RSV-induced inflammation using siRNA technique"
    Richard F. Lockey
  • "Pharmacogenetics of inhaled corticosteroid"
    Lanny J. Rosenwasser
  • "WHO-GARD: The global alliance against chronic respiratory diseases"
    Jean Bousquet
  • "Hot topics in allergic diseases"
    Takeshi Fukuda

Click here for more information.

日本アレルギー学会に引き続いてソウルにおいても韓国アレルギー学会とWAOの共同会議が開催される。

wafWorld Allergy Forum

The management of allergic emergencies is a major concern for allergists worldwide. Asthma, anaphylaxis and angioedema will all be reviewed during the upcoming World Allergy Forum Symposium scheduled for Sunday, 12 November 2006 – 8:30 a.m. – 10:00 a.m., at the American College of Allergy, Asthma and Immunology (ACAAI), Annual Scientific Meeting in the Pennsylvania Convention Center, Ballroom AB in Philadelphia, PA, USA.

Michael A. Kaliner, President, WAO will moderate this program of renowned international speakers.


bankok
World Allergy Congress 2007 Symposium

2-6 December 2006
Bangkok, Thailand

'Global Issues in Allergy: Answers for a Worldwide Problem'
Allergic Emergencies


Acute and Severe Asthma
Bob Q. Lanier, North Texas Institute for Clinical Trials
Fort Worth, Texas, USA

Anaphylaxis: Causes and Treatments
Ruby Pawankar, Nippon Medical School
Tokyo, Japan

Angioedema
Michael A. Kaliner, Institute for Asthma and Allergy
Wheaton, Maryland, USA


New WAO Conversation

Hear Dr. Sally Wenzel share her knowledge on what makes a severe asthmatic different and how to adjust your thinking to manage these refractory patients.

I-PODで聴くアレルギー疾患解説。今月はデンバーのサリーウェンツェル教授の講義である。


Sign up for On-Line Journal Subscription –

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


And In Other News (その他のニュース)

Allergy Book Reviews

Mast cells in allergic diseases. Chemical Immunology and Allergy. Vol. 87
Editors: Saito, H.; Okayama, Y.
Karger Basel 2005

List Price: $178.25 USD
Available from: Karger

訳者が編集し、一年前に発売された本の紹介である。WAOのウェブ編集委員の一人でもある訳者が自分でWAOのウェブに売り込むのを潔しとしなかった。発売後一年たって、担当のオーストラリアの先生に読んで頂いた。執筆陣が若手一流研究者であるので内容には自信があるが、ほめていただいている。最先端の情報が掲載されており、購読対象はこの分野に興味のある研究者が主体であるが、それ以外の読者にも興味深いとしている。ありがたい。


Reviewer:
Ron Walls MD, PhD
University of Sydney, Sydney, NSW, Australia

Description:
Mast cells were originally described by Paul Ehrlich in the 19th Century, and their role in the immediate allergic response is well-known. Their importance in the allergic reaction was reflected in a debate scheduled for a major meeting in Allergy some years back on whether mast cells or T cells were the most important cells in the allergic reaction! Less well recognized is their importance in other aspects of immunological reactions including innate immunity, angiogenesis and tissue remodelling. Mast cells are derived from haematopoietic progenitors in the bone marrow but spend their lives as tissue-dwelling effector cells.

Purpose:
This book is designed to bring together the latest work on mast cells from their development through to their physiological functions. The contributors are active workers in the area and bring the most current information to their contributions. The information is detailed but presented in a readable and engaging form.

Audience:
This volume would be of most value to those who are working actively in the field of research or tertiary clinical practice or who are involved in teaching immunology and biology and want an up-to-date source of information about these interesting cells outside of their immediate area of interest

Features:
There are comprehensive accounts of the regulation of mast cell development and activation. This is followed by a detailed description of mast cell factors and receptors and their roles in allergic and immunologic conditions. Their localization in airway smooth muscle bundles characterizes asthma. Their roles in airway smooth muscle hyperplasia and in airway remodeling in asthma and their involvement in allergic rhinitis are well covered. The model of “mast cell knock-in” mice and its contribution to understanding of late phase reactions and chronic allergic inflammation is well covered. The species differences in these cells are emphasized, and the point is made that one cannot extrapolate from mouse to human mast cells. This is one factor that has made the study of these cells so difficult.

Assessment:
The subject matter is presented lucidly, even to a non-specialist, and although a multi-author book, the quality of the presentations is uniformly very high. This is an authoritative account of our current knowledge of this fascinating cell, not only in immediate hypersensitivity reactions, but also in other aspects of the immune response. The book can be warmly recommended to researchers, teachers and clinicians who need ready access to an up-to-date, high level of scientific material, and to students about to embark on a postgraduate study of immunology or allergy. It is an important addition to the personal library of serious students and should be available for reference in libraries and in clinical and research departments.


Immune System Disorders Sourcebook (Second Edition)

Edited by: Joyce Brennfleck Shannon

自己免疫疾患を中心とした全身性の免疫疾患に関する本で86章に分かれて簡潔に記載されている。教科書として最適であるそうだ。

List Price: $78.00 USD
Available from: Omnigraphics

Reviewer:
Roger W. Fox, MD
University of South Florida Health Sciences Center, Tampa, FL, USA

Description:
The text is a compendium of brief reviews in each of the 86 chapters on basic consumer health information about many of the disorders of the immune system. These include immune system function and response, diagnosis of immune disorders, information about inherited immune diseases, acquired immune diseases and autoimmune diseases. The book covers a wide range of immune-related disorders, such as primary immunodeficiencies, acquired immunodeficiency syndrome, Lupus, multiple sclerosis, type 1 diabetes, rheumatoid arthritis and Graves disease. Treatments and coping skills for individuals with immune disorders are discussed. A valuable directory of organizations in Chapter 86 provides information and help for patients with immune disorders and their families.

Purpose:
This text serves as a quick overview resource of a wide range of immunological disorders for patients and healthcare providers

Audience:
This sourcebook on the immune system disorders should find a home in many of the public and medical libraries as an important resource for individuals and specific support groups. Physicians’ offices could provide this text to patients and their families for general knowledge on immune problems and as a resource to find on-line information about various disorders.

Features:
The book has a directory of organizations with immune disorders information, complete with address, phone and FAX numbers and websites.

Assessment:
This book is an excellent resource text for libraries and healthcare providers’ offices, plus support groups and patient advocates would find this book very helpful for medical information and for identifying national organizations with a focus on a specific immune disorder.


Find more allergy book reviews on the WAO Website here.

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 www.worldallergy.org

WAO世界アレルギー機構は世界中のアレルギー学会の連携をはかり、臨床、研究、教育等の向上と充実を目指すことを使命としています。是非、www.worldallergy.org にアクセスして下さい。

World Allergy Organization (WAO)
Secretariat
555 E. Wells Street, Suite 1100
Milwaukee, WI 53202-3823
Email: info@worldallergy.org

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