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November Medical Journal Review
WAO Now: What's New in the World of WAO
And In Other News . . .

November World Medical Journal Review

Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, reviewed premier November medical journal articles for practicing allergists. WAOのWeb編集委員長、南フロリダ大学ロッキー教授による11月の医学雑誌レビュー

1. THE NATURAL HISTORY OF ASTHMA IN CHILDREN AND ADULTS BY DRS CHARLES REED & GAIL SHAPIRO
Dr. Reed lists six predictors of persistence and severity of adult asthma to include continued exposure to allergens, including occupational agents, older age onset, aspirin sensitivity, socioeconomic status, smoking and coexisting disease (COPD, bronchiectasis, etc.). For children, both Drs. Reed and Shapiro include a family history of atopy, early sensitization, and airway hyper-responsiveness. Dr. Shapiro also includes early onset; low lung function; female sex; smoking, passive smoking and smoking during pregnancy; and maternal asthma. Dr. Reed, for children, covers more frequent and severe asthma, onset during school age, increased serum IgE, increased URIs, lack of contact with other children, parenting problems and childhood psychological problems. Dr. Shapiro concludes, regardless of the prognosis of childhood wheezing, that parents of children with both low and high risk for persistent disease can be comforted and reassured if they follow an action plan for daily maintenance treatment and for acute exacerbations of asthma. Editor’s comment: Two outstanding articles discuss the vexing problem of who will and who will not have persistent childhood and adult asthma. Reed CE, J Allergy Clin Immunol 2006; 118: 543; the late Dr. Shapiro GG: 562.

小児喘息から成人喘息への移行に影響する因子に関する2つの論文紹介。Charles Reed氏および先日、急逝された故Gail Shapiro氏による。2つとも重症度、IgE値、呼吸器感染症の頻度、他の子どもとの接触の機会、養育に関する問題などが関連しているとしている。Shapriro氏はさらに予後に拘わらず日常的な喘息管理を徹底させることで親子の喘息の持続に関する不安を和らげることが可能であることを強調している。

2. THE EFFECTS OF A MONOCLONAL ANTIBODY DIRECTED AGAINST TUMOR NECROSIS FACTOR-α IN ASTHMA
Infliximab (I) (Remicade), a recombinant human-murine chimeric monoclonal antibody that specifically and potently binds and neutralizes the soluble TNF-α homotrimer and its membrane-bound precursor, was used in a DBPC, parallel-group study in 38 patients with moderate asthma treated with inhaled corticosteroids who were symptomatic during a run-in-phase. Lung function, symptoms and inhaled β2-agonist usage were monitored. There was no change in morning PEF, however, it was associated with a decrease in mean diurnal variation in PEF at wk 8 (p = 0.02). Likewise there was a decrease in exacerbations in the treatment group (p = 0.01) and an increased probability of freedom from exacerbation with time (p = 0.03). I decreases levels of TNF-α and other cytokines in sputum supernatants. No serious adverse events occurred. Editor’s comment: I looks like a promising therapy for moderate asthma. Erin EM, et al. Am J Respir Crit Care Med 2006; 174: 753.

吸入ステロイドを使用している中等症の喘息患者38名に対し、抗TNFα抗体(Infliximab)療法をDBPCにて試した。その結果、Infliximabは有意に発作消失期間、8週間後のピークフロー値、喀痰中のTNFαなどのサイトカイン濃度を減少させた。

3. URINE LEUKOTRIENE E4 LEVELS ARE ASSOCIATED WITH DECREASED PULMONARY FUNCTION IN CHILDREN WITH PERSISTENT AIRWAY OBSTRUCTION
This study was designed to assess the relationship between daily variability in urinary leukotriene E4 (LTE4) levels and daily lung function in 50 children with moderate to severe asthma primarily taking an inhaled corticosteroid (ICS) and long-acting β-agonist (LABA). Urinary LTE4, monitoring of FEV1, and albuterol use were measured. Daily variability in LTE4 levels is associated with clinically significant decreases in pulmonary function. In children who demonstrate a response associated with an increase in urinary LTE4 levels, leukotriene receptor antagonists protect against daily FEV1 decreases, which may be greatest in those with persistent airway obstruction despite the use of combined ICS and LABA therapy. Editor’s comment: Asthma is a complex disease and what is good for the goose may not be good for the gander. Rabinovitch N, et al. J Allergy Clin Immunol 2006; 118: 635.

50名の中等症~重症喘息小児患者において尿中ロイコトリエンE4濃度は小児の持続的な気道閉塞FEV1と比例した。吸入性ステロイド薬とLABAの組み合わせにも拘わらず持続的な気道閉塞が見られる場合はロイコトリエン受容体拮抗薬の使用を考慮すべきである。

4. THE COMPLEMENT INHIBITOR ECULIZUMAB IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
Patients (87) underwent randomization to receive either placebo (P) or eculizumab (E, a humanized monoclonal antibody against terminal complement protein C5 that inhibits terminal complement activation) intravenously. Subjects were given 600 mg weekly for four weeks, followed one week later by a 900-mg dose and then 900 mg every other week through week 26. Stabilization of hemoglobin levels in the absence of transfusions was achieved in 49% of treated vs. P (P<0.001). During the study, no packed red cells were administered to the treatment group vs. 10 to the P group (P<0.001). E reduced intravascular hemolysis vs. P (P<0.001). There was a statistical improvement in quality of life in the treated group (P<0.001). There were no serious adverse events considered to be treatment-related. Editorfs comment: E is an effective therapy for PNH. Hillmen P, et al. N Engl J Med 2006; 355: 1233.

発作性夜間血色素尿症は、溶血性貧血のひとつであり根治療法は確立されていなかった。本研究において補体活性化を阻害するC5蛋白質に対するヒト化モノクローナル抗体eculizumabを使用したところ輸血回数などの症状が有意に改善した。

5. CONCLUSIONS FROM THREE SEPARATE PAPERS FROM THE EUROPEAN HEALTH SURVEY
The first study determined cat allergen levels in approximately 3,000 mattresses during home visits in 22 communities. It showed that people who do not own cats may be exposed to high levels of cat allergen in their homes, particularly if they live in communities with high cat ownership. The second article determined that there are large qualitative and quantitative differences in house dust mite allergen levels partially explained by geographic and housing characteristics. They recommend that mite allergen levels could be reduced by replacing mattresses and increasing ventilation of the bedroom, particularly in the winter. The third article, perhaps the most interesting, determined that selective avoidance of cats subsequent to the onset of asthma and allergy was observed for childhood cat-keeping and adult cat acquisition, implying that part of the protective effects of childhood cats on asthma and allergy can be attributed to selective avoidance. Editorfs comment: Allergen avoidance is complex in spite of the best intentions of the physician and patient. Heinrich J, et al. J Allergy Clin Immunol 2006; 118: 674; Zock J, et al: 682; Svanes C, et al: 691.

Cat allergen level: Its determinants and relationship to specific IgE to cat across European centers
Distribution and determinants of house dust mite allergens in Europe: The European Community Respiratory Health Survey II
Do asthma and allergy influence subsequent pet keeping? An analysis of childhood and adulthood

ヨーロッパで行われた疫学調査に関する3つの論文の紹介。最初の論文は「ネコを飼育していない人でもネコを飼育することの多い地域に住んでいる場合、大量のネコ抗原と接触する可能性がある」ことを述べている。2つめの論文は地域や家屋の条件によりダニ抗原量は大きく異なることを述べている。著者らは冬の間に寝室の換気やマットレスの入れ替えが効果的であるとしている。3つめは、ペットを飼育しているアレルギー疾患患児や喘息患児がその後のペット飼育に及ぼす影響について検討した。子どものころにネコアレルギーがある場合はネコを手放すことが多く、そしてそれはネコに対するIgE抗体を有意に減少した。しかし、成人ではペットを手放さないことが多く、また、ネコ以外の犬や鳥に関してはペット放棄の影響を少なかった。

6. PHARMACOLOGIC AND ANTI-IgE TREATMENT OF ALLERGIC RHINITIS ARIA UPDATE (IN COLLABORATION WITH GA2LEN)
This document updates the ARIA sections on the pharmacologic and anti-IgE treatment of allergic rhinitis literature published between January 2000 and December 2004. Oral H1-antihistamines, intranasal corticosteroids, intranasal H1-antihistamines, intranasal chromones, and anti-IgE mab achieved level evidence A, for seasonal and perennial rhinitis in children and adults. Anti-leukotrienes achieved an A level for seasonal rhinitis but not for perennial rhinitis for both groups. For gpersistent rhinitis,h all treatments for both groups were either A or B except for the intranasal chromones which could not be rated. Editorfs comment: Physicians have a variety of different, proven treatments for seasonal and perennial rhinitis. Bousquet J, et al. Allergy 2006; 61: 1086.

アレルギー性鼻炎ガイドラインARIAにおける抗IgE抗体療法の位置づけに関する論文。2004年12月までの臨床試験において、H1抗ヒスタミン経口および点鼻薬、ステロイド点鼻薬、抗IgE抗体療法はエビデンスレベルAの評価とされた。季節性鼻炎に対するロイコトリエン拮抗薬の効果はAであったが通年性鼻炎に対する効果は認めなかった。クロモリン点鼻薬の効果は認めることはできなかった。

7. A 10 YEAR ASTHMA PROGRAMME IN FINLAND: MAJOR CHANGE FOR THE BETTER
A National Asthma Program was undertaken in Finland from 1994-2004 to improve asthma care and prevent increased costs. Although the incidence of asthma is increasing, the number of hospital days fell by 54%, mortality decreased, and absolute numbers for disability pensions, allowances for days off work, and need for rehabilitation all decreased 30 to 50%. Most impressive was that there was an annual reduction in cost per patient of 50%. The authors conclude that diseases such as asthma require a multi-disciplinary action program with a broad commitment by the health care system and society. Editorfs comment: Optimal care and compliance led to decreased morbidity and mortality from asthma. Haahtela T, et al. Thorax 2006; 61: 663.

1994年からの10年間、フィンランドにおいていくつかの治療法や生活指導を組み合わせた喘息治療プログラムが実施された。その結果、喘息罹患率は増加したものの、入院日数は54%減少、死亡率やリハビリを要する症例は30-50%減少した。

8. PERSISTENCE, ADHERENCE, AND EFFECTIVENESS OF COMBINATION THERAPY AMONG ADULT PATIENTS WITH ASTHMA
These authors compared persistence, adherence and effectiveness between patients with asthma, 16 to 44 yrs, using either a combination of an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) in one inhaler or the individual use of two different inhalers with similar medications. It is a retrospective 1-to-1 matched cohort of newly treated asthmatics selected from a database between 1999 and 2002. Using a variety of statistical models, persistence of use of medication fell to 10% and 5% after 12 months for combination and concurrent user, respectively. Combination users were found to be 17% less likely to stop their treatment, filled on average 0.9 more prescriptions per year, and were found to be 17% less likely to have a moderate to severe asthma exacerbation. Editorfs comment: When an ICS and LABA are used in one inhaler vs. two separate inhalers, compliance and outcomes improve. Marceau C, et al. J Allergy Clin Immunol 2006; 118: 574.

喘息治療法に対するアドヒアランスやコンプライアンスについて検討した。その結果、吸入性ステロイド薬とLABAを別々に使用した場合に比して、それらの合剤ではコンプライアンスと症状の改善がみとめられた。

9. IMMUNOTHERAPY WITH A RAGWEED-TOLL-LIKE RECEPTOR 9 AGONIST VACCINE FOR ALLERGIC RHINITIS
These authors conducted a randomized DBPC trial of a vaccine consisting of Amb a 1, conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC) in 25 ragweed allergic subjects. They received six weekly injections of AIC vs. placebo before the ragweed season. The vaccine did not reduce the albumin level in nasal-lavage fluid but had positive effects on peak season rhinitis scores (P=.0006), peak-season daily nasal symptoms scores (P=0.02), and midseason overall quality-of-life (P=0.05). It also induced a transient increase in Amb a 1-specific IgG antibody and suppressed the seasonal increase in Amb a 1-specific IgE antibody. Some clinical benefits and seasonal specific IgE antibody responses were observed in the subsequent ragweed season. Editorfs comment: More studies are needed but AIC may be useful to treat allergic rhinitis. Creticos PS, et al. N Engl J Med 2006; 355: 1445.

Th1細胞を増加させるToll様受容体9のリガンドCpGをブタクサ花粉に化学結合させたワクチンの臨床治験の結果である。この花粉CpG結合物を6回シーズン前に注射するだけで、その年のみならず翌年の花粉症状を有意に改善させた。この効果は予想に反して、IL-10とは無関係であった。Th1サイトカインに関連していると思われれる。

10. KILLED MYCOBACTERIUM VACCAE SUSPENSION IN CHILDREN WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
This multi-centered study determined the effects of intradermal injection of killed M. vaccae (0.1 or 1 mg) on patients, aged 5-16, with moderate to severe AD. The primary end point was change in severity at 12 weeks using a six area, six sign, atopic dermatitis score. Secondary end points included changes in disease extent, patientfs global assessment and childrenfs dermatologic QOL index. In 166 randomized patients, M. vaccae was no more effective than placebo in ameliorating the severity of AD. Editorfs comment: Decreased exposure to mycobacterial infection does not seem to be a reason for the increased incidence of atopic dermatitis. Berth-Jones J, et al. Clinical and Experimental Allergy 2006; 36: 1115.

結核菌死菌ワクチンの小児アトピー性皮膚炎に対する効果の検討が行われた。166名の患児に対して効果が検討されたが、プラセボを凌ぐ効果は得られなかった。

11. PROBIOTICS IN THE PREVENTION OF ANTIBIOTIC-ASSOCIATED DIARRHEA (AAD) IN CHILDREN: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Six randomized, placebo-controlled trials (766 children) were included in this meta-analysis to determine whether or not treatment with probiotics vs. placebo reduced the risk of AAD. The results show that such treatment reduced the risk of AAD from 28.5% to 11.9% (RR, 0.44, 95% CI 0.25 to 0.77, random effect model). Reduction of risk was associated with the use of Lactobacillus GG, S. boulardii or B.lactis & Str. thermophilus. The authors conclude that for every seven patients that would develop AAD while on antibiotics, one fewer would occur if they also received probiotics. Editorfs comment: Give cultured yogurt or probiotics. They decrease AAD in children. Szajewska H, et al. J Pediatr 2006; 149: 367.

抗生物質により生じる下痢症に対してプロバイオティックスは有効であった。

12. PSYCHIATRIC ADVERSE EFFECTS OF CORTICOSTEROIDS
Two large meta-analyses found that severe reactions occurred from systemic corticosteroids in nearly 6% of patients and mild to moderate reactions in about 28%. Side effects include mood, cognition, sleep and behavior problems (frank delirium or even psychosis). The most common are euphoria and hypomania. Dosage seems to be most related to the incidence of adverse effects. In severe cases, where these drugs cannot be reduced, antipsychotics or mood stabilizers may be required. Editorfs comment: An excellent review of a problem that allergists/immunologists face all the time. Warrington TP, Bostwick JM. Mayo Clin Proc 2006; 81: 1361.

全身性ステロイドの精神症状に関する副作用についての論文。多幸症が最も多かった。


WAO Now: What's New in the World of WAO

WAO Secretariat Staff Change

Stanley Mandarich, WAO’s Executive Director, will be leaving the organization this month to return to Toronto, Ontario, Canada, where he will assume the position of Executive Director of the Canadian Anesthesiologists’ Society. We wish Stan well and thank him for serving WAO so ably since 2004.

We are delighted to welcome Charu Malik, PhD, as our new Executive Director of WAO from mid-January 2007. Charu, a native of India, brings considerable experience in association management; her international knowledge will be a great asset to the organization.

WAOの秘書官を長く努めていたStanley Mandarichはカナダに帰国し代わってCharu Malik博士が着任した。

WAO Long-Term Research Fellowship

Congratulations to Dr. Andrea Vereda-Ortiz, who has been awarded the first WAO Long-Term Research Fellowship, to commence in 2007. Dr. Vereda will undertake a fellowship with Dr. Hugh Sampson at Mount Sinai Hospital, New York, to study "Comparative characterization of legume reactivity between patients of Spain and the United States." WAO received a number of excellent applications, and we thank all those who applied for their interest in this program.

WAOがサポートするフェローシップの案内。


WAO Short-Term research fellowship

Dr. Eleonara Dehlink has completed her WAO Short-Term Research Fellowship at the laboratory of Dr. Edda Fiebiger, Boston’s Children’s Hospital. The fellowship funding was used to help Dr. Dehlink learn new techniques for her research project “Is Fc-epsilon-RI an antigen uptake/presentation receptor in the intestinal mucosa involved in the initiation of allergic immune responses in the gastro-intestinal tract? an in vitro approach". To read a report on Dr. Dehlink’s work, click here.


WAO Educational Needs Survey

The World Allergy Organization’s educational programs are designed to assist Member Societies by providing educational materials that bring together the expertise and experience of allergists worldwide. We are currently surveying our members, and would value the comments of the readers of WAO News and Notes about their own educational needs and preferences. Please click here to complete the short, on-line survey.

WAOの教育プログラムに関するアンケートを実施している。ご協力いただきたい。


Future World Allergy Congresses

For all future WAO Congresses, the WAO Congress Council has recently recommended that WAO solicit proposals from specific world regions on a rotational basis. This will ensure a fair, worldwide representation over the years. The WAO Board of Directors met recently and determined that Europe would be the preferred site of our 2013 Congress. The final decision on a location within Europe will be made at the WAO House of Delegates meeting during the 2007 WAC in Bangkok.

WAO会議は2005年のミュンヘンの後、2007年がバンコク、2009年がブエノスアイレス、2011年がカンクンで開催されるが、2013年はヨーロッパで開催されることが望ましいと決議された。

Future locations:
2-6 December 2007 - Bangkok, Thailand (http://www.congrex.com/wac2007/ )
2009 - Buenos Aires, Argentina
2011 - Cancun, Mexico


World Allergy Forum Held at the 2007 ACAAI Annual Scientific Meeting:

World Allergy Congress 2007 Symposium
"Global Issues in Allergy: Answers for a Worldwide Problem"
Allergic Emergencies

Our international faculty was chaired by Michael A. Kaliner and provided a worldwide update on allergic emergencies. The first speaker, Bob Q. Lanier (Fort Worth, TX, USA), presented an update on acute and severe asthma, and the presentation by Ruby Pawankar (Tokyo, Japan) focused on anaphylaxis. The symposium was concluded by Michael A. Kaliner (Wheaton, MD, USA), who discussed angioedema.

Click here to view abstracts and presentation slides.

バンコクでのWAO会議におけるシンポジウムの紹介。


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

Allergy Book Reviews

Ultrastructure of Mast Cells and Basophils
Ann M Dvorak
ISBN-10:3-8055-7864-4
ISBN-13:978-3-8055-7864-6

List price: $135.50 USD
Available from: Karger

Reviewer:
Ross Boadle
Institute of Clinical Pathology and Medical Research and Westmead Millennium Institute, Westmead, NSW, Australia

Description:
This monograph reviews the work undertaken in the laboratories of the author and her collaborators between 1991 and 2001. It follows upon an earlier (1991) monograph and begins by reinforcing the ultrastructural definitions that allow differentiation of the (closely related) mast cell and basophil, in mouse, guinea pig and human.

Purpose:
The well ordered text explores the ultrastructural localization of cytokines, proteases, histamine, Charcot-Leyden crystal protein and other factors in the organelles of mast cells and basophils. The scope of this text then broadens to include the role of vesiculo-vacuolar organelles and their role in the trans endothelial secretory pathway.

Audience:
While this book will prove to be of broad based interest to medical professionals, its most significant value should be to those researching the basic science of immunology and allergy and the interaction of mast cells in tissue based systems.

Features:
There is a balanced blend of both well established electron microscopy methodology (including immuno-gold labeling), together with enzyme affinity gold techniques and ultrastructural in situ hybridization. Techniques are adequately described and effectively referenced. The 185 illustrations are of consistently good quality.

Assessment:
For these specialized individuals, the book will find its way into personal libraries. This text should also reside on the shelves of the libraries of those institutions where basic ultrastructural cell research is undertaken.

マスト細胞と好塩基球の電子顕微鏡による構造学の教科書である。30年以上この分野の第一人者として活躍しているAnn Dvorak氏による。


Asthma in the Workplace, 3rd Edition

David I. Bernstein, et al.
ISBN 0824729773

List price: $249.95
Available from: CRC Press

Reviewer:
Mark Glaum
University of South Florida College of Medicine, Tampa, FL, USA

Description:
This is the third edition of a reference text that reviews the key components of work‑related asthma. The book is organized into four main sections, including: General Considerations, Assessment and Management, Specific Agents Causing Occupational Asthma with a Latency Period, and Specific Disease Entities and Variants.

Purpose:
The purpose is to provide the clinician with a detailed reference covering all relevant aspects of occupational asthma, especially those relating to disease mechanisms, causative agents, clinical diagnosis and treatment.

Audience:
Discussion is targeted to clinicians and clinical researchers who have an interest in occupational lung disease. Specialists most likely to utilize this resource include pulmonologists, allergists, clinical immunologists, and any physician with an interest in work‑related illnesses. Fellows in training will find this book to be an excellent reference text for the evaluation of occupational airway complaints.

Features:
Each chapter is logically organized, well‑written and concludes with an extensive bibliography. Over 100 tables and figures are clearly presented serving to illustrate relevant points. An excellent appendix is included that lists known causative agents in occupational asthma along with key references. A complete index concludes the text.

Assessment/Comparison:
This book provides a comprehensive review of clinically relevant topics in occupational asthma written by nationally and internationally recognized experts in the field. This text is an outstanding reference resource for the clinician, clinical scientist or clinical fellow with an interest in work‑related asthma.

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.orgWAO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。

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