WAO News and Notes - Medical Reviews
Volume 5, Issue 8 Reviews - August 2008
Announcing the WAO Web Site's new look at www.worldallergy.org
Medical Journal Reviews

Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief reviewed premier medical journal articles for practicing allergists. ロッキー教授によるアレルギー臨床に携わる実地医家向けの今月の医学雑誌レビュー

To read translations of past Medical Journal Reviews, click here.

1. Comparison of adjustable-and fixed-dose budesonide/formoterol (BF) pressurized metered-dose inhaler and fixed-dose fluticasone propionate/salmeterol (FS) dry powder inhaler in asthma patients
This is a randomized, open-label, multicenter study of 1225 subjects, 12 yrs and older, with moderate-to-severe persistent asthma. After 10 to 14 days of current therapy, patients were randomized 2:1 to fixed-dose BF (160/4.5 µg x 2 inhalations [320/9 µg] twice daily) or fixed-dose FS (250/50 µg x 1 inhalation twice daily) for one month, after which the fixed-dose FS group continued therapy and the fixed-dose BF group was randomized 1:1 to fixed-dose BF or adjustable-dose BF (adjustable from two inhalations [320/9 µg] twice daily to two inhalations [320/9 µg] once daily or four inhalations ([640/18 µg] twice daily) for six months. There were no significant between-group differences for asthma exacerbations (primary objective), asthma symptoms, or lung function during the 7-month treatment period. The authors conclude that adjustable-dose and fixed-dose BF versus fixed-dose FS demonstrate no difference in asthma control or tolerability. Editor's comment: Most patients respond to comparable fixed-dose inhalers containing both a long-acting beta-agonist and a glucocorticosteroid. Busse WW, et al., NCBI 2008 Jun;121(6):1407-14

12歳以上の喘息患者1225名に対してブデソニド・フォルモテロール合剤(用量可変を含む)とフルチカゾン・サルメテロール合剤のランダム化比較試験を行った。その結果、両群間に差を認めなかった。

2. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
Aluminium adjuvants are used in human and animal vaccines worldwide. The authors show that aluminium adjuvants activate an intracellular innate immune response system, called the Nalp3 (also known as cryopyrin, CIAS1 or NLRP3) inflammasome. Production of the pro-inflammatory cytokines, interleukin-1β and interleukin-18 by macrophages, in response to alum in vitro, require intact inflammasome signaling. Mice deficient in Nalp3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) or caspase-1 fail to mount a significant antibody response to an antigen administered with aluminium adjuvants, whereas the response to complete Freund's adjuvant remains intact. Editor's comment: Understanding how aluminium adjuvants work will help design more specific adjuvants. Eisenbarth SC, et al., Nature 2008; 453:1122.

水酸化アルミニウムゲル(アラム)は動物実験においてIgE抗体産生など免疫反応を増強させるアジュバントとしてしばしば使用されるが、そのメカニズムは不明であった。著者らはNalp3を欠損したマウスにおいてアラムによる抗体産生増強やインターロイキン1βやインターロイキン18産生の低下を認めたことにより、アラムに反応する分子としてNalp3を同定した。

3. T-cell regulation in chronic paranasal sinus disease
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a TH2-skewed eosinophilic inflammation, whereas chronic rhinosinusitis without nasal polyps (CRSsNP) represents a predominant TH1 milieu. Nasal mucosa tissue from 13 patients with CRSsNP, 16 with CRSwNP, and 10 control patients were analyzed. The authors demonstrate a decreased expression of FOXP3 in nasal polyp tissue, reflecting a deficiency or dysfunction of Treg cells, in CRSwNP. In addition, low levels of TGF-β1 protein expression and an upregulation of the transcription signals for TH1 (T-bet) and TH2 (GATA-3) subpopulations point to a defective suppression of their upregulation by Treg cells. The authors conclude by stating that a lack of Treg cells may contribute to the severe persistent TH2-skewed inflammation in CRSwNP, not present in the CRSsNP group. Editor's Comment: A lack of Treg cells may contribute to the pathogenesis of nasal polyps in CRSwNP. Van Bruaene N, et al., JACI 2008; 121:1435.

鼻茸を合併する慢性副鼻腔炎(CRSwNP)はTH2優位の好酸球が浸潤が特徴であるが、鼻茸を合併しない慢性副鼻腔炎(CRSsNP)はTH1優位である。13名のCRSsNP鼻粘膜と16名のCRSwNP鼻粘膜、10名の対照患者組織を比較した結果、CRSwNPではFOXP3陽性制御性T細胞数とTGF-β1値が有意に低下していた。

4. Induction and effector functions of TH17 cells
The TH17 cell, a third subset of effector T helper cells, is the subject of intense research to understand their role in immunity and disease. An excellent review of emerging data suggests that the TH17 cells have an important role in host defense against specific pathogens, some of which include Propionibacterium acnes, the Gram-negative Citrobacter rodentium, Klebsiella pneumoniae, Bacteroides spp. and Borrelia spp., the acid-fast Mycobacterium tuberculosis, and fungi such as Candida albicans. They are also potent inducers of autoimmunity and tissue inflammation. In addition, differentiation factors responsible for TH17 generation reveal an interesting reciprocal relationship with regulatory T (Treg) cells, which prevent tissue inflammation and mediate self-tolerance. Editor's comment: A fantastic review of a subject of interest to all allergists/immunologists. A must read. Bettelli E, et al., Nature 2008; 453:1051.

自己免疫疾患発症を促進するヘルパーT細胞はTH1>細胞ではなくインターロイキン17を特異的に産生する新たに見いだされたサブセットであるTH17細胞であることがあきらかになっている。炎症を促進するTH17細胞と制御性T細胞とのバランスなどが注目されている。TH17細胞に関する優れた総説であり、すべての免疫アレルギー研究者が読むべき論文である。

5. Ciclesonide (C) improves measures of small airway involvement in asthma
16 mild-to-moderate asthma patients were randomized to receive five weeks treatment with placebo (P) vs 320 µg C once daily. Small airway parameters were assessed. Seven received P and nine C. Alveolar exhaled nitric oxide (eNO) and computed tomography (CT) measurements of expiratory lung function after methacholine (MCh) challenge decreased significantly with C vs P. It did not affect mean expiratory flow between 25 and 75% of forced vital capacity (FVC), percentage fall in FVC at the provocative dose of adenosine-5'-monophosphate or MCh causing a 20% decrease in FEV1, and single-breath nitrogen closing volume. The authors conclude that C exerts anti-inflammatory effects on the small airways. Editor's comment: Optimal treatment for some patients with asthma may require that the entire airway be treated, including the small airways. Cohen J, et al., Eur Respir J 2008; 31:1213.

CTスキャンや呼気NO、メタコリン吸入試験などを指標に16名の喘息患者に対するシクレソニドの効果をプラセボと比較した。その結果、シクレソニド投与群では、末梢気道閉塞関連指標が有意に改善した。

6. Prevention of Herpes Zoster
The June 6, 2008 issue of the Morbidity and Mortality Weekly Report (MMWR) has an excellent article on recommendations for herpes zoster (shingles) vaccination. It is recommended for all persons aged ≥ 60 yrs who have no contraindications, including those with previous episodes of herpes zoster or those who have chronic medical conditions, regardless of their history of varicella (chickenpox) or serologically proven varicella immunity. Medical conditions include chronic renal failure, diabetes mellitus, rheumatoid arthritis, and chronic pulmonary disease. Since this is a live, attenuated vaccine, it should not be given to patients who are immunosuppressed or with immunodeficiency. Editor's comment: Pediatricians traditionally administer vaccines to children; allergists/immunologists should be the primary, or one of the specialty groups, that administer vaccines to adults. Harpaz R, et al., MMWR 2008; 57.

帯状疱疹ウイルスワクチンに関する優れた論文である。60歳以上のものは、抗体の有無や既往に拘わらず免疫不全でない限り全員受けるべきである。特にリウマチや腎臓病、慢性肺疾患などで持続的に薬剤投与を受けている場合は積極的に接種すべきである。

7. Molecular Origins of Cancer; Cancer Immunology
The immune system can respond to cancer cells by either reacting against tumor-specific antigens (molecules unique to cancer cells) or against tumor-associated antigens (molecules expressed differently by cancer vs normal cells). This knowledge has stimulated the invention of many new therapeutic antibodies, cell-based treatments, and vaccines which are currently being used in clinical practice. This therapy should result in increased and improved cancer treatment and possibly, eventually, even prevent cancer. Editor's comment: This is an excellent article on tumor immunology and the immunologic reagents approved by the FDA for cancer therapy. Finn OJ, N Engl J Med 2008; 358:2704.

癌免疫に関する優れた総説である。癌特異的抗原や正常組織に比較し癌組織で発現が増強している癌関連抗原のいずれかに反応する免疫システムが存在する。この免疫システムをもちいた治療開発が期待されている。

8. The ABCs of Asthma Control
The authors describe four easy steps to achieve asthma control in the ambulatory practice setting: 1) a standardized assessment of asthma symptoms using a 5-question assessment tool, the Asthma Control Test (ACT), 2) a simple mnemonic, AIRESMOG, that provides a systematic review of the comorbidities and clinical variables that contribute to uncontrolled asthma, 3) directed patient education, and 4) a schedule for ongoing care. The authors conclude that almost all patients can achieve good asthma control using this approach. The AIRESMOG Mnemonic stands for: A - Allergy and Adherence to therapy, I - Infection and Inflammation, R - Rhinitis and Rhinosinusitis, E - Exercise and Error in diagnosis, S - Smoking and pSychogenic factors, M - Medications (β-blockers, angiotensin-converting enzyme inhibitor, aspirin), O - Occupational exposures, Obesity, and Obstructive sleep apnea, G - Gastroesophageal reflux disease. Editor's comment: This AIRESMOG Mnemonic will help make asthma the most treatable of all chronic diseases. Thorsteinsdottir B, et al., Mayo Clin Prac 2008; 83:814.

喘息コントロールのABCと題した論文である。簡単で覚えやすい救急処置について記載されている。

9. Subspecialty differences in asthma characteristics and management
2407 patients (72%) with asthma were treated by allergists and 935 (28%) by pulmonologists in the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Patients treated by pulmonologists vs allergists were more likely to be African-American, less educated, have lower incomes, have more severe asthma, and use short-acting β-agonist and systemic corticosteroids more regularly. Although evidence of allergic disease was prevalent in both groups, those treated by allergists were more likely to be skin tested and receive immunotherapy. Those treated by pulmonologists also were more likely to report greater health care use for asthma in the previous 3 months. Editor's comment: Subspecialty differences do exist between allergists/immunologists and pulmonologists. Chen H, et al., Mayo Clin Proc 2008; 83:786.

アレルギー専門医に罹る喘息患者と比較して、呼吸器科医に罹る患者はアフリカ系米国人で教育や収入が低いレベルであり、重症で短時間作動型β2刺激薬や全身性のステロイド薬の投与を受けている場合が多かった。

10. Update on mechanisms of allergen injection immunotherapy
Allergen immunotherapy is indicated for allergic rhinitis, allergic asthma and Hymenoptera hypersensitivity. Unlike pharmacotherapy, it provides long-term clinical benefits, such as long-term disease remission, prevention of new atopic sensitizations and a reduction in disease progression from rhinitis to asthma. Editor's comment: This state-of-the-art review is outstanding. James LK, Durham SR, Clin Exp Allergy 2008; 38:1074.

アレルゲン免疫療法に関する最新知見に関する優れた総説である。

World Allergy Congress (WAC) 2009 - Buenos Aires, Argentina,  6-10 December 2009

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Allergy Book Review

Janeway's Immunobiology 7th Edition
Author: Kenneth Murphy, Paul Travers, Mark Walport
ISBN: 9780815341239

すでに定評のある免疫学教科書の第7版の紹介である。図や表がわかりやすく、電子ファイルも利用できるので、私も講義スライドによく利用している(訳者)。7版からはアニメーションスライドも提供されているとのこと。

Available from: Taylor and Francis Group
List Price: $95.95

Reviewer:
Dr Denise C. Hsu, BscMBBS(UNSW)
Immunology Registrar
Campbelltown Hospital
NSW, Australia

Description
This is the 7th edition of a highly regarded comprehensive textbook of basic immunology. It covers the different mechanisms utilized by the immune system to protect the host from infections as well as other aspects of immunology including allergy, autoimmunity, transplant and tumour immunology. The 7th edition has been updated throughout, with new information on topics such as NK cells, Toll-like receptors, viral evasins, innate receptors and celiac disease.

Purpose
The purpose of this book is to present in a comprehensive, yet concise manner the current knowledge on basic immunology from the viewpoint of the host's interaction with potentially harmful microbes in its environment.

Audience
This book is intended to be an introductory immunology text book for medical students, post graduate students and scientists interested in the field of immunology. It is especially useful for immunology trainees seeking current and accurate information on the immune system and for immunologists for quick reference and teaching preparation.

Features
The book is divided into 6 parts with a total of 16 chapters. It begins with an introduction on immunobiology and innate immunity, followed by sections on antigen recognition, development of lymphocyte receptor repertoires, adaptive immune response, immune system in health and disease and evolutionary history of the immune system. The appendix contains sections on diagnostic tools and summary tables on CD antigens and cytokines. There is also an easy to use glossary.

The chapters are well ordered and the language is clear and succinct. Ample well designed diagrams and tables illustrate complex ideas. Summary paragraphs further consolidate the topics discussed. Each chapter concludes with revision questions and a well organized list of references.

The accompanying CD containing animations, voice over narration and all the figures in the book, in the format of PowerPoint presentation is an invaluable resource.

Assessment
The 7th edition of Immunobiology is one of the best basic immunology textbooks available. Materials are well organised and clearly presented. It is a must have for clinicians and researcher who strive to have an understanding of basic immunology.

Find more allergy book reviews on the WAO Website here.

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