WAO News & Notes

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

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January World Medical Journal Review

Prof. Richard F. Lockey, MD, and WAO Web Editor-in-Chief, reviewed premier January medical journal articles for practicing allergists. WAOのWeb編集委員長、南フロリダ大学Richard F. Lockey教授による1月の医学雑誌レビュー

1. Rapid effects of inhaled corticosteroids in acute asthma
Seventeen studies (470 adults and 663 children and adolescents) met the criteria for inclusion in this review of treatment with inhaled corticosteroids (ICS) within one to four hours of presentation of an asthma exacerbation. Final outcomes were admission and ED discharge rates. After the 2- to 4- hour protocol, a greater reduction of admission rate was observed in trials that used multiple doses of ICS, especially when compared with placebo (odds ratio{OR}, 0.30; 95% confidence interval {CI}, 0.16 to 0.55). ICS patients improve more rapidly when compared with placebo or systemic corticosteroids (SCS) increasing the probability of early ED discharge (OR 4.70; 95% CI, 2.97 to 7.42; p = 0.0001). Spirometric and clinical measures improved as early as 60 minutes with ICS. Benefits were obtained only when patients received multiple doses of ICS with ß-agonist compared with placebo or SCS. In conclusion, ICS used early in multiple doses administered in time intervals of < or = to 30 minutes over 90 to 120 minutes are especially beneficial. Editor's comment: High dose ICS plus β-agonists used within four hours on multiple occasions for acute asthma effectively decreases morbidity from severe asthma exacerbations. Rodrigo GJ, Chest 2006; 130: 1301

喘息急性発作にステロイド薬はしばしば使用されるが、吸入性ステロイドの有効性に関しては不明な点が多かった。本研究は470名の成人喘息患者、663名の小児喘息患者を対象に発作に対する吸入性ステロイド薬の有効性について救急室における入院と退院の割合や呼吸機能などを指標に検討している。その結果、プラセボと比較し、さらに驚くべきことに全身性のステロイド薬投与との比較においても、吸入性ステロイド薬は急性発作に対し、より有効で２－４時間後の入院の率は低下した。呼吸機能も改善した。

2. Effects of continuing or stopping alendronate (A) after 5 years of treatment
One thousand and ninety-nine (1099) postmenopausal women with a mean of five years of prior A treatment were randomized to A, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo (P) (n = 437) for five years. Compared with A, switching to P resulted in declines in bone mineral density (BMD) at the total hip (P< .001) and spine (P<.001), but mean levels remained at or were above pretreatment levels 10 years earlier. The cumulative risk for nonvertebral fractures was not significantly different between the two groups. Those on A had significantly lower risks of clinically recognized vertebral fractures (5.3% for P, 2.4% for A) but no significant reduction in morphometric vertebral fractures (11.3% for P, 9.8% for A). The authors suggest that the discontinuation of A after five years does not significantly increase the fracture risk, however, women at high risk of clinical vertebral fractures may benefit by continuation of A. Editor's comment: Physicians who treat asthma and allergic and immunologic diseases need to know how to diagnosis and treat osteopenia and osteoporosis. SG. Black DM, et al. JAMA 2006; 296: 2927. Editorial, Colón-Emeric C. JAMA 2006; 296: 2968.

全身性ステロイド薬治療では骨粗鬆症が問題となる。この研究は閉経後の女性を対象に骨代謝ホルモンalendronateの有効性について検討している。その結果、有意な改善は認めなかったとしているが、背椎の骨折の合併症に関しては減少させる可能性もあるとしている。

3. Long-term proton pump inhibitor (PPI) therapy and risk of hip fracture
This is a nested, case-control study using a research database from the United Kingdom. The cohort consisted of users of PPI therapy versus nonusers of acid suppression drugs older than 50 years. Similar nested, case-control analysis for histamine 2 receptor antagonists was performed. The adjusted odds ratio (AOR) for hip fractures associated with more than one year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30-1.59). For long-term high dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90; P<.001). The risk increased with duration of PPI therapy, i.e., up to four years. The authors conclude that PPI therapy significantly increases the risk of hip fracture, possibly secondary to acid suppression and decreased calcium absorption. Editor's comment: The risk-benefit of PPI therapy needs to be considered. Individuals with asthma commonly have gastroesophageal reflux disease. Using the lowest effective PPI dose and increasing consumption of dairy products, calcium supplements with meals, and vitamin D therapy make sense. Yang Y-X, et al. JAMA 2006; 296: 2947.

プロトンポンプ阻害薬は骨折のリスクを増強させることを示した研究成果である。

4. Asthma, influenza, and vaccination - Review
Influenza (I) viruses, like other viruses, exacerbate asthma (AS) and are frequently associated with hospitalization. Inactivated I vaccine (V) does not exacerbate AS. Likewise, medium- or high-dose inhaled or short-term systemic corticosteroids (CS) do not affect antibody responses to I A-antigens. High-dose inhaled CS may affect the response, but this is controversial. There is still a question of whether inactivated I V prevents the exacerbation of asthma. Live attenuated I V, given by nasal spray, is better accepted by children and is more efficacious. Universal I vaccination of all children will facilitate control of epidemic I and provide an infrastructure for control of future I pandemics. Editor's comment: I V is indicated for all asthmatics, and I V immunization of all children will facilitate control of this disease. Glezen W P, JACI 2006; 118: 1199.

喘息患者におけるインフルエンザワクチン注射の是非に関する総説である。

5. Anti-IL-5 (MEPOLIZUMAB) therapy for eosinophilic esophagitis
This is an open-label, phase I/II, safety and efficacy study of anti-IL-5 in four adult patients with eosinophilic esophagitis (EE) with longstanding dysphagia and esophageal strictures. They were given three infusions of anti-IL-5 without a change in current therapy. Peripheral blood eosinophils and percent of CCR3+ cells decreased by 6.4- and 7.9-fold (P<.05), respectively, as did mean and maximal esophageal eosinophilia, (P< .001) and (P<.05), respectively. Patients' clinical outcome and quality of life improved (P = .03) and therapy was tolerated. IL-5 may be a therapeutic option for EE. Editor's comment: More studies are needed with anti-IL-5 for EE. Stein ML, et al. J Allergy Clin Immunol 2006; 118: 1312.

好酸球性食道炎に対する抗IL-5抗体の効果に関する研究成果である。喘息に対する効果と異なり、臨床症状も改善した。

Numbers 6 & 7 were reviewed by Gary Hellermann, PhD, University of South Florida, Tampa, Florida　

以下６と７のレビューはGary Hellermann先生による。

6. Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells
RANKL, the ligand of RANK (receptor activator of NF-κB), is up-regulated in keratinocytes when skin is UV irradiated and binds to RANK expressed on dendritic cells of the skin, the Langerhans cells (LC). The evidence comes primarily from experiments on transgenic mice over-expressing RANKL, and these mice show 2-3 times greater systemic numbers of CD4+CD25+ T regulatory cells (Tregs) than the wild type. The Tregs from RANKL-transgenic mice suppress effector T cells and produce characteristic biomarkers such as IL-10. The authors conclude that the peripheral expansion of Tregs results from an increase in cutaneous RANKL, which stimulates LC via binding to RANK, to promote proliferation of Tregs. Editor's comment: Cutaneous stimulation of LC by increasing RANKL in the presence of a specific antigen may provide a new treatment for suppressing allergic inflammation. Loser K, et al. Nature Medicine 2006; 12: 1372.

皮膚に紫外線を照射するとケラチノサイトにRANKLが強く発現する。このRANKLを強制発現させたマウスではCD4+CD25+ 制御性T細胞（Treg）の数が２－３倍に増加し、より多くのIL-10が産生された。RANKLとは内因性のTregアジュバントなのかも知れない。

7. Natural killer T Cells and CD8+ T Cells are dispensable for T Cell-dependent allergic airway inflammation (AAI)
Das et al compare the contribution of T helper type 2 (Th2) cells, natural killer T cells (NKT) and CD8+ T cells to AAI. Ovalbumin-sensitized transgenic mice with gene knockouts that eliminated CD4+ T cells show no eosinophil infiltrate or increased mucus in the lungs after ovalbumin challenge. However, mice deficient in NKT and CD8+ T cells had ovalbumin-induced AAI comparable to the wild type. Therefore, the authors conclude that NKT cells with or without memory CD8+ cells are not required for AAI. The authors of an earlier paper (Akbari et al.), which supports the role of NKT and DC8+ cells in AAI, reply that airway hyper-responsiveness (AHR) is a better measure of asthma than eosinophilia and mucus production and cite two studies supporting involvement of NKT cells in AHR. They point out that while allergen-specific Th2 cells are necessary in allergic rhinitis, the AHR characteristic of asthma appears to involve NKT cell regulation of other factors in the lower respiratory tract. Editor's comment: The complexity of the immune system is legendary, and the jury is still out on the relative contributions of all players. Das J, et al. Nature Medicine 2006; 12: 1345.

NKT細胞とCD8陽性T細胞はTh2細胞に依存したアレルギー性気道炎症に不可欠である。編集者はまだ評決は出ていない(Jury is still out)とコメントしている。

8. Validation of current joint AAAAI & ACAAI guidelines for antibody response to the 23 pneumococcal vaccine (PPV) using a population of HIV-infected children
This case-controlled study compared changes in PPV AB titers in 95 immunocompetent children versus 22 immunodeficient HIV-infected children, ages 2 to 15 years. Authors confirm the proposed recommendations of a 4-fold increase in titers after PPV immunization for at least 50% of the serotypes tested (6 out of 12) as adequate responses in children between 2 and 15 years. For children who have previously received the 7-pneumococcal conjugate vaccine, positive responses for two out of four serotypes not included in this vaccine are considered adequate. Editor's comment: This study outlines criteria to accurately identify children who lack optimal responses to one immunization with PPV. Kamchaisatian W, et al. JACI 2006; 118: 1336. Potential conflict of interest: authors are USF colleagues of RFL.

ＨＩＶに感染した小児に対する肺炎球菌ワクチンの有効性等について検証し、有効でないものも存在すると述べている。

9. Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis (AD)?
This review article summarizes the evidence associated with house dust mite (HDM) allergens as an allergic trigger factor for AD. They offer evidence that the enzymatic activity of HDM facilitates allergenic penetration into the impaired, epidermal skin barrier of AD inducing both immediate- and delayed-type reactions which contribute to the impairment of AD. The authors review data on specific immunotherapy (SIT) and AD. They conclude that the value of SIT for treatment of AD is uncertain at this time. Editor's comment: This is must reading for all physicians who treat severe AD. More controlled studies are necessary on treatment efficacy of IT for AD. Bussmann C, et al. JACI 2006; 118: 1292.

アトピー性皮膚炎に対するアレルゲン特異的免疫療法の是非に関する論文である。現時点では有効性を示すエビデンスはないとのことである。

10. Why do we develop food allergies?
This author reviews how the immune system detects the differences between food and pathogens in a systematic discussion on how food represents a special challenge for the immune system of the gut, which is designed to guard against invaders. In-utero immunologic responses, secretory immunoglobulin A and oral tolerance all contribute to the immunologic acceptance of multiple food antigens. The author reviews work that demonstrates that oral tolerance to food is directly linked to the development of CD25+ Treg cells. He goes on to state that the current increase of allergies in industrialized countries is a small price to pay for the remarkable reduction in infant mortality, provided by the intermission of pathogens through improved hygiene. Editors comment: A wonderful update on the pathogenesis of food allergy. Brandtzaeg P, American Scientist 2006; 95: 28.

耐性ができるのが当たり前の食物に対して何故、アレルギーになってしまうのかということについて記載された総説である。

11. High prevalence of aeroallergen sensitization among infants of atopic parents
A birth cohort of infants was first identified from birth records and enrolled in this study if a parent reported allergic respiratory symptoms and had a positive skin prick test (SPT) to a common aeroallergen. At one-year, these infants were tested to the same 15 aeroallergens. Of 680 infants, 28 % were SPT positive to one or more aeroallergens and/or food and 18 % positive to one or more aeroallergens (9.7 %, pollen; 7.5 %, molds; 4.3 % house dust mite and/or cockroach; and 3.4% dog and/or cat). Sixty-six percent remained positive at 2-years. The authors conclude that infants born to atopic parents who are SPT positive are at increased risk for aeroallergen sensitization during infancy, which persists to age 2-years and suggest that SPT before age 2 may be indicated to identify such children. Editor's comment: Allergic sensitization starts early in life to both food and inhalant allergens. LeMasters G, et al. J Pediatrics 2006; 149:505. Potential conflict of interest: Drs.Grace LeMasters and James Lockey are relatives of RFL.

アレルギー疾患の親から出生した児を対象とした出生コホートの結果が記載されている。一歳の時点で28%の児が皮膚プリックテスト陽性であった。

12. Immunologic response to administration of standardardized dog allergen extract at differing doses
Cluster immunotherapy was administered to 28 patients with dog allergy randomly assigned to placebo or an acetone-precipitated extract containing 0.6 µg, 3.0 µg, or 15 µg Can f 1 per 0.5 ml maintenance dose. Results show a significant dose-dependant response in suppression of titrated skin prick tests and delayed cutaneous responses. Dog-specific IgG4 increased significantly in both high-dose and low-dose therapy, and there was a dose-dependant suppression of secreted TNF-α and increase in secreted TGF-ß. Likewise, there was a dose-dependant trend in suppression of secreted IL-4 with a significant decrease from baseline in the high-dose group. No changes occurred in symptom scores: lymphocyte proliferation; secreted IFN-γ , IL-10, or IL-5; or intracellular cytokine production. The lack of clinical response was attributed to a misunderstanding in the conduct of nasal challenges resulting in suboptimal dosing. The authors conclude that a maintenance dose of 15 µg of Can f 1 produces the greatest and most consistent immunologic response. Editor's comment: Immunotherapy with similar doses of Fel d 1 and Can f 1 produces similar immunologic responses. Lent AM, et al. JACI 2006; 118:1249.

イヌアレルゲンCan f 1による免疫療法の有効性について記載されている。15 µg の維持量が必要であった。

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

World Allergy Forum
"A Global Perspective on Genetics, the Environment and Allergy"


2007 AAAAI Annual Meeting
Monday, February 26, 2007, 4:45 pm - 6:00 pm
San Diego Convention Center
Upper Level, Room 32 AB

Moderator:
Thomas A. E. Platts-Mills, USA

Co-Moderator:
Michael A. Kaliner, USA

Is Early Exposure to Allergen Protective?
Adnan Custovic, United Kingdom

How Does the Environment Influence Genetic Responses?
Robert F. Lemanske Jr., USA

Environmental Intervention in the Management of Allergic Diseases
Erika Von Mutius, Germany

2月に開催される米国アレルギー学会の中のWAOシンポジウムの紹介である。


2007 March GLORIA Placements
 

その他の3月のGLORIAの活動の紹介。

Scientific Meeting of the Association of Allergology and Clinical Immunology of Serbia and Montenegro
22-24 March 2007
Belgrade, Serbia

International GLORIA Faculty:
Todor Popov
Presentations:
Module 7: Angioedema
Module 9: Diagnosis of IgE Sensitization

South Carolina Society of Allergy, Asthma, and Immunology
March 23-25, 2007
Charleston, South Carolina
US GLORIA Faculty:
Allen P. Kaplan
Presentations:
Module 2: Allergic Conjunctivitis
Module 8: Anaphylaxis

GLORIA is supported through unrestricted educational grants from:

The WAO Henning Løwenstein Research Award 2007
Call for Applications

若い研究者に対する研究奨励の案内。

The WAO Henning Løwenstein Research Award is a biennial award given to a young scientist who has shown excellence within the field of allergy. WAO and ALK-Abelló will present the award at the World Allergy Congress in Bangkok, 2-6 December 2007.

The winner will receive EURO 20,000 together with a travel grant to attend the Congress.For application guidelines visit www.alk-abello.com and click on "The WAO Henning Løwenstein Research Award."

Deadline: 30 June 2007

New Synopsis
Drug Allergies are the focus of the latest educational synopsis to be posted on the WAO Web site. Written by Bernard Thong, MBBS, MRCP (UK), FAAAAI, with contributions from Cassim Motala, MD FCPAED(SA) FACAAI FAAAAI , and Daniel Vervloet, MD FAAAAI, the synopsis provides a comprehensive overview of immunological and non-immunological adverse drug reactions. To read this new synopsis in WAO's Allergic Diseases Resource Center, click here.

新しいアレルギー関連小冊子の案内。薬剤アレルギーが加わった。

WAO Conversations:
We have the pleasure of announcing four new interviews with well-respected allergists. Take a moment to listen to them sharing their extensive knowledge.
 

• Prof. Stephen Durham - Mechanisms of Immunotherapy
• Dr. Thomas Platts-Mills - Indoor Allergen Control
• Prof. Carlos Baena-Cagnani - History and Vision of the World Allergy Organization
• Dr. Harold Nelson - How do you properly mix Allergen Vaccines?

MP3プレイヤーにダウンロードして聴く、WAO conversationの紹介。

El-Ghoneimy Short-Term Fellowship Report
Dr. Dalia El-Ghoneimy from Cairo, Egypt, spent her WAO Short-Term Research Fellowship in the laboratory of Prof. G. Walter Canonica in Genoa, Italy, studying skin prick testing in the early diagnosis of atopy in infants and children and immunotherapeutic modalities. The objective of her fellowship was to receive the necessary training to enable her to identify the major allergens to which infants in Egypt are sensitized and the possible immunotherapeutic interventions needed. To read Dr. El-Ghoneimy's report on her fellowship, click here.

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

Allergy in Practice
Author: Johannes Ring
Editor: Marion Philipp
ISBN #: 978-3-540-00219-2

List price: $129.00 USD
Available from: Springer Berlin Heidelberg

NOTE: The book, Allergy in Practice, was reviewed by two different reviewers, as follows.

Johannes Ring教授らによる教科書Allergy in Practiceの紹介文です。２名の批評が掲載されています。

First review of Allergy in Practice
Reviewer: Ron Purcell, MD
University of South Florida College of Medicine and James A. Haley
Veterans Hospital, Tampa, FL, USA

Description:
Allergy in Practice is a concise yet remarkably thorough overview of allergic disease and provides the reader with a basic understanding of the physiology, diagnosis, and treatment of commonly encountered allergic conditions. This is an updated version of the 2nd edition printed in 1988 and reflects the many changes in the field over the past 20 years.

Purpose:
This book is written to provide the reader with a better understanding of the recognition and treatment of allergic diseases commonly encountered in the clinical setting. It does not cover immunodeficiency, rheumatology or other immunologic conditions except as they relate specifically to allergy.

Audience:
Medical students, physicians in training, and other health care professionals looking for an introduction to the clinical practice of allergy will find this to be an excellent resource. It also serves well as a reference for health care professionals who want rapid access to clinically useful information regarding the field of allergy.

Features:
Without a doubt, the book's strong point is the author's exceptional ability to present information in a concise, straightforward manner. Despite being only 276 pages and measuring 25 X 17 cm, the book covers nearly every aspect of allergy in such a way that the reader can quickly grasp even difficult concepts. Each section is clearly delineated and rarely exceeds two pages; many are only one or two paragraphs. Despite this brevity, explanations are thorough and complete. The clinical sections are organized logically and make generous use of tables, so differential diagnosis, common physical findings, and other practical information can be quickly accessed. Extensive cross referencing of sections allows the reader to easily locate related concepts or conditions. Additional chapters covering allergen immunotherapy and diagnostic techniques, such as skin testing, provide insight into how these are accomplished by specialists trained in these procedures.

Assessment:
Anyone wishing to increase their understanding of the diagnosis and management of allergic disease in a concise, readable format will find this to be an excellent resource.
 

Second review of Allergy in Practice
Reviewer: Salvador Gala, MB BS PhD
University of Sydney

Description:
Prof. Ring states his book evolved from a series of information leaflets and short chapters for residents rotating through his Allergy Division. Thus, the underlying theme reflecting a detailed but concise introduction to allergic disease is evident throughout Allergy in Practice. There are the standard chapters on allergic mechanisms, clinical evaluation, diagnostic tests and therapy. However, grouping of allergic disorders within the main body of the text is predominantly according to the Gell and Coombs classification, wherein clinical information appears within a scheme of pathophysiology. Nevertheless, this approach works quite well; the reviewer was easily able to navigate throughout the different subsections of the book when searching for specific pieces of information. As the sole author, Prof. Ring eschews those problems of excess, irrelevant detail and redundancy so commonly observed in multi-authored comprehensive texts.

Purpose:
Allergy in Practice provides the trainee and non-specialist reader with a detailed but concise introduction to the field of allergy. Prof. Ring covers all major subject areas relevant to the basic science and clinical management of allergic disease. It is, in essence, a textbook - but written in a user-friendly style.

Audience:
Whilst easy to follow, Allergy in Practice is pitched at the specialist level. This book is, therefore, ideal as a study aid for allergy trainees and residents undertaking an allergy rotation and as a refresher for allergy specialists. Non-allergist physicians requiring specific information on allergic disorders will more readily find answers here, rather than trying to negotiate larger comprehensive allergy texts.

Features:
The positive qualities to Allergy in Practice are plentiful. Descriptions of individual allergic disorders are detailed but concise. Those aspects of basic science chosen for review are all clinically relevant. High-quality color photography is included throughout the book to demonstrate important clinical, radiological and histological points within the main text. Prof. Ring makes frequent use of schematic multi-color diagrams to convey important concepts without, however, becoming entrenched in overly complicated detail. Lists and tables accompanying the text are useful for clinical reference because they achieve a balance between sufficient detail and conciseness. References are very selective and included on the basis of clinical relevance.

Does the book have any drawbacks? Its advantages are at the same time its limitations. The reader will still need access to comprehensive textbooks and journals for details of rare conditions, in-depth reviews, and more up-to-date information. Inclusion of an Appendix serves to partly address these issues by directing the reader towards additional sources of information.

Assessment:
Prof. Ring's publication represents a clinically useful, high-quality 'entry-level' allergy textbook. As summarized by Prof. Platts-Mills in his foreword to Allergy in Practice, Prof. Ring provides a comprehensive but well planned description of allergic disorders "that are either very common or just common." Allergy in Practice is designed for use as an introductory textbook, to be studied cover-to-cover and complemented by reading of current literature.

Find more allergy book reviews on the WAO Website here.