May World Medical Journal Review （医学雑誌レビュー）
Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, reviewed premier March medical journal articles for practicing allergists. 南フロリダ大学ロッキー教授による5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す。
1. LONG-TERM INHALED CORTICOSTEROIDS (ICS) IN PRESCHOOL CHILDREN AT HIGH RISK FOR ASTHMA
Two-hundred and eighty-five children, two or three years old, with a positive asthma predictive index were observed for one year and then given either fluticasone propionate (FP), 88µg 2x d, or placebo for two years. They were followed one additional year on no study medication or placebo. Treatment was associated with a significantly greater proportion of episode-free days, a lower rate of exacerbations, and less supplemental use of controller medications. At the end of the fourth year, the height increase was 0.7 cm less in the treatment group (P = 0.008). Even though the FP group did better during the two years of treatment, FP treatment did not alter the development of asthma or lung function during a third treatment-free year. Editor's comment: ICS are effective to treat pre-school children with asthma but do not alter long-term outcomes. Guilbert TW, et al. N Engl J Med 2006; 354: 1985. Gold DR, Fuhlbrigge AL, (editorial) 2058.
2. INTERMITTENT INHALED CORTICOSTEROIDS IN INFANTS WITH EPISODIC WHEEZING
Two-hundred and ninety-four infants were randomly assigned to receive budesonide or placebo at their first episode of wheezing. Proportion of symptom-free days was similar in both groups as was persistent wheezing. The outcomes were not affected by the presence or absence of atopic dermatitis, and the mean duration of the acute episodes was identical in both groups and independent of respiratory viral status. Height and bone mineral density were not affected in either group. Inhaled budesonide has no short-term benefit during episodes of wheezing during the first three years of life nor does it affect the progression from episodic to persistent wheezing. Editor's comment: Finding a way to prevent these episodes may be the best solution for early onset episodic wheezing. Bisgaard H, et al. N Engl J Med 2006; 354: 1998. Gold DR, Fuhlbrigge AL, (editorial) 2058.
上記論文と同じNEJMの号に掲載された論文である。生後6ヶ月の喘鳴を来した小児に喘鳴出現後３日目よりブデソニドを吸入させた結果、プラセボ吸入と比較し、全く効果がなかったことが記載されている。訳者注：この試験でもかなり限定された患児が対象 とされている。生後1ヵ月程度で喘息症状が強く現れて いることからも、これらの症例は遺伝的要因が強い 症例であったと考えられる。また本試験では、発作 が起きて3 日目後から吸入ステロイド薬を使用して いるが、アレルギー性の気管支喘息の場合、発作後 6 〜 24 時間の間に遅発反応が起き、3 日後の時点で は種々の炎症細胞がすでに活性化された状態にある ことから、この時点から吸入ステロイド薬を投与し ても効果は期待できない。すなわち、発作が起きて 3 日目後から吸入ステロイド薬を投与するのは遅すぎると思われる。さらに、本試験で使用されたブデソニド製剤は乳幼児によく使用される懸濁液ではなく、成人用の製剤をスペーサーをもちいて使用している。以上の点を考慮すると、この論文の解釈は相当、慎重に行うべきである。
3. EFFECT OF CODEINE ON OBJECTIVE MEASUREMENT OF COUGH IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
Twenty-one patients with physician-diagnosed stable COPD with cough (77% male; mean age, 68 years; mean predicted FEV1, 53%; median smoking history, 43.5 pack-years) were studied in a DBPC crossover study. Cough frequency, cough seconds/hours, citric acid cough threshold, and subjective measurements were obtained. Codeine phosphate 60 mg or matched placebo was administered, in random order, at the start of each cough recording (0 and 12 hours). There were no significant differences in median time spent coughing, challenge thresholds, or subjective cough measures for codeine vs. placebo. Editor's comment: Codeine was no better than placebo to treat cough in patients with COPD. Smith J, et al. J Allergy Clin Immunol 2006; 117: 831.
4. SELF-ADMINISTRATION OF C1-INHIBITOR CONCENTRATE IN PATIENTS WITH HEREDITARY OR ACQUIRED ANGIOEDEMA (A) CAUSED BY C1-INHIBITOR DEFICIENCY
Thirty-one patients who had frequent A attacks participated in an hereditary or acquired C1-inhibitor deficiency study. Patients were trained to self-administer IV C1-inhibitor concentrate on-demand (31 patients) or prophylactically (12 patients). Mean follow-up was 3.5 years. Patients were able to self-administer the concentrate. The time between the onset of an attack and relief or complete resolution of symptoms in the on-demand group was shortened to 2.2 hours vs. 7.9 hours (baseline date) in the on-demand group. Prophylactic treatment decreased the A attack rate from 4.0 to 0.3 (baseline data) attacks per month. Editor's comment: Self-administered IV C1-inhibitor concentrate is effective both on-demand and prophylactically. Levi M, et al. J Allergy Clin Immunol 2006; 117: 904
5. RESPIRATORY SYNCYTIAL VIRUS (RSV), AIRWAY INFLAMMATION, AND FEV1 DECLINE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
RSV RNA was detected by PCR in 32.8% of 241 sputum samples collected quarterly over two years from 74 patients with stable COPD. Patients in whom RSV was more frequently detected (> than 50% of samples RSV PCR-positive, n = 18) had higher airway inflammation and faster FEV1 decline over the study period compared with those with less frequent detection of RSV. This relationship was independent of smoking status, exacerbation frequency, and lower airway bacterial load. Persistent RSV in COPD is associated with airway inflammation and accelerated decline in FEV1. Editor's comment: RSV infection may accelerate lung function decline in COPD. Wilkinson TMA, et al. Am J Respir Crit Care Med 2006; 173: 871.
6. HIGH LEVELS OF MEDICAL UTILIZATION BY AMBULATORY PATIENTS WITH VOCAL CORD DYSFUNCTION (VCD) AS COMPARED TO AGE- AND GENDER-MATCHED ASTHMATICS
Twenty-five ambulatory patients with VCD were gender matched to 25 control patients with moderate persistent asthma. Total physician visits and subspecialty care visits were significantly greater among the VCD vs. the asthma cohort. Both groups had comparable utilization of prescriptions, frequency of hospitalizations, and urgent care visits. The authors conclude that VCD patients use significantly more medical services and similar pharmaceutical assets compared to patients with moderate persistent asthma. Editor's comment: VCD must be ruled out in every patient who presents with symptoms of asthma. Mikita J, Parker J, Chest 2006; 129: 905. Christopher K, (editorial) 842.
7. CYSTEINYL LEUKOTRIENE RECEPTOR 1 PROMOTER POLYMORPHISM IS ASSOCIATED WITH ASPIRIN-INTOLERANT ASTHMA (AIA) IN MALES
Cysteinyl Leukotrienes (CysLTs) are important in the pathogenesis of AIA. Three CysLTR 1 promoter single nucleotide polymorphisms (SNPs) were associated with AIA risk in males, and males with AIA had significantly higher frequencies of the minor alleles (T,C,G) at the three SNPs than male control subjects. Moreover, the two common three-SNP haplotypes were also associated with AIA risk in males. The ht1 [C-A-A] haplotype was associated with decreased risk and ht2 [T-C-G] haplotype with increased risk. Males were younger than females in the AIA group. Male AIA patients carrying ht2 [T-C-G] may be at greater risk to develop AIA at an earlier age. There were no significant associations of CysLTR1 genotypes or three-SNP haplotypes with AIA risk in female patients. Genetic variants of CysLTR 1 are associated with AIA in a Korean population and may modulate CysLTR 1 expression. Editor's comment: Understanding the genetics of AIA will go along way in understanding its pathogenesis. Kim S-H, et al. Clin Exp Allergy 2006; 36: 433.
8. SAFETY OF SPECIFIC IMMUNOTHERAPY (SIT) USING A FOUR-HOUR ULTRA-RUSH INDUCTION SCHEME IN BEE AND WASP ALLERGY
Sixty-seven Hymenoptera allergic individuals received 80 outpatient courses of ultra-rush SIT. In 78 courses (97.5%), the maintenance dose of 111.1 µg was reached within four hours and was tolerated in 82.5% without any adverse reaction. Allergic reactions were observed in 17.5% (n = 14), all of which were local reactions and none of which was life-threatening. Ultra-rush IT to Hymenoptera (wasp and honeybee venoms) was safe, convenient,and completed within 4 hours in an outpatient setting. Editor's comment: Venom immunotherapy using a four-hour-ultra-rush IT schedule was safe. Roll A, et al. J Investig Allergol Clin Immunol 2006; 16: 79.
9. INTRANASAL DELIVERY OF THE CYTOPLASMIC DOMAIN OF CTLA-4 USING A NOVEL PROTEIN TRANSDUCTION DOMAIN PREVENTS ALLERGIC INFLAMMATION
CTLA-4 is a negative regulator of T-cell activation. CTLA-4 was fused to a novel protein-transduction domain in human transcriptional factor Hph-1 to suppress allergic inflammation. The Hph-1-ctCTLA-4 fusion protein (FP) inhibited the production of IL-2 and downregulated CD69 and CD25. Intranasal administration of the FP, reduced infiltration of inflammatory cells, secretion of TH2 cytokines, serum IgE levels, and airway hyper-responsiveness in a mouse model of allergic airway inflammation. Thus, CTLA-4 might block the TH2 cell-polarized T-cell activation and potentially could be used intranasally to treat allergic asthma. Editor's comment: Another molecule which could possibly be used intranasally to downregulate allergic inflammation. Choi J, et al. Nature Medicine 2006.
CTLA-4はCD28と競合し、また抑制性T細胞を介して、T細胞の活性化を制御する。著者らはCTLA-4の細胞内ドメイン蛋白質をつくり、マウスの喘息モデルに投与したところTh2の活性化が抑えられ、アレルギー反応が抑制されたことを報告している。訳者注：しかし、同様なコンセプトで開発されマウスとサルでは有用性が証明されたヒト化抗CD28抗体は、ヒトに対し、治験薬として使用したところ、注射後、1-2時間で被験者が頭痛、血圧低下を訴え多臓器不全に陥った。そして、４名が危篤で２名が重体であると報告されている（Nature 2006; 440.853）。
10. AN ANTIBODY-DEFICIENCY SYNDROME DUE TO MUTATIONS IN THE C19 GENE and INHERITED AND SOMATIC CD3ζ IN A PATIENT WITH T-CELL DEFICIENCY
Four patients with mutations in the CD19 gene had increased susceptibility to infection, hypogammaglobulinemia, and normal numbers of B-cells. The CD19 gene is responsible for generating CD19, a protein on the B-cell surface which forms a complex with other proteins that participate in activation of B-cells by antigens. In a SECOND article a child with greatly increased susceptibility to viral, bacterial, and fungal infections was found to have inherited a homozygous germ-line mutation of the CD3ζ gene. CD3ζ is a component of the CD3 T-cell-receptor complex and is essential for T-cell activation. These articles are accompanied by a superb editorial entitled, "Disabled Receptor Signaling and New Primary Immunodeficiency Disorders." Editor's comment: These articles and the editorial are must reading for physicians who do not understand the multiple defects that cause T-cell and B-cell immunodeficiencies. van Zelm MC, et al. N Engl J Med 2006; 354: 1901, Rieux-Laucat F, et al. 1913, Rudd CE, (editorial) 1874.
11. REVIEW OF THE USE OF INTRAVENOUS GAMMA GLOBULIN (IGIV) IN HUMAN IMMUNODEFICIENCY DISEASES
This is an evidence-based review of the use of IGIV for primary immunodeficiency,
secondary immunodeficiency, autoimmune diseases, asthma, and neurological disorders. Editor's comment: Article is full of wonderful tables and references and is excellent reading. Orange JS, et al. J Allergy Clin Immunol 2006; 117: S525
WAO Member Society Spotlight - Austrian
Society of Allergology and Immunology (OGAI)
Dear colleagues and friends,
Here is the news from the Austrian Society of Allergology and Immunology (ÖGAI). We really enjoyed hosting so many of you at the Congress of the EAACI in Vienna, June 10 ? 14, 2006.
The booth of the Austrian Society of Allergology and Immunology in the "National Village" of this EAACI congress was a real success. You may remember that in our booth we offered not only information about Vienna but also delicious "Mozartkugeln," the famous sweets created in honor of Wolfgang Amadeus Mozart!
Last but not least, we would like to announce a newly funded Doctoral College CCHD (Cellular Communications in Health and Disease) at the Medical University Vienna, where we offer 24 doctoral positions for a newly established, high-quality PhD program. We cordially invite you to suggest that your best students apply for these truly attractive positions by the July 30, 2006 deadline.
The program offers cutting-edge education in the field of Neurobiology, Vascular Biology, Immunology and Inflammation Research and integrates basic, applied, and clinical sciences, as well as a huge spectrum of experimental techniques.
Admitted PhD Students will receive funding for at least three years including support to visit international conferences and specialized workshops. Applicants must hold a final degree in the diploma studies of Medicine, Dentistry, or in any scientific/technical subject-related diploma (such as cell or molecular biology) by the commencing term of the program.
Further information on research topics and courses, as well as application forms, is available at: www.phd-cchd.at. Applications must be submitted by email to: email@example.com.
Prof. Erika Jensen-Jarolim, MD
WAO delegate of the ÖGAI
WAO Now: What's New in the World of WAO
Introducing New GLORIA Modules
The World Allergy Organization is excited to announce the launch of two new modules of our flagship educational program, GLORIA? (Global Resources in Allergy?) at the meeting of the Singapore Society of Immunology, Allergy & Rheumatology, 15 July 2006, Tan Tock Seng Hospital.
Module 8: Anaphylaxis
15 July 2006 from 8:20 a.m. ? 9:20 a.m. in the TTSH Theatrette
Module 9: Diagnosis of IgE Sensitization
15 July 2006 from 10:40 a.m. ? 11:40 a.m. in the TTSH Theatrette
GLORIA Faculty: Cassim Motala, South Africa
New on the WAO Web Site
In WAO Conversations, hear Allen P. Kaplan share his informal ideas on the treatment of Urticaria. To hear the interview, click here.
I-podで聞く、WAO conversationの第２弾です。Allen P. Kaplan先生による蕁麻疹に関する最新の考え方が述べられています。簡単に紹介すると、「蕁麻疹が急性であれば食物などに関するアレルギープリックテストを行う価値はあるが、慢性症状の場合、ほとんど意味はない」「ピロリ菌やビタミンB12欠乏が原因とは思えない」その他、慢性特発性蕁麻疹に対するロイコトリエン拮抗薬やサイクロスポリン、プレドニン治療の是非について考えが述べられています。医学英語リスニングの練習にどうぞ。
We are pleased to announce two new Interactive Case Reviews that are based on Clinical Case Reports published in the ACII-JWAO.
- "The approach to recurrent upper respiratory infections," presented by Patrick J. DeMarco and Richard F. Lockey
- "Exercise -induced anaphylaxis," presented by Alexander T. Vu and Richard F. Lockey
To read the reviews, then make your diagnosis and learn if you agree with the experts, click here.
WAO Short-Term Research Fellowships Awarded
WAO has awarded three Short-Term Research Fellowships of $2,500 to enable young researchers to visit centers abroad and learn techniques to further their research programs. Congratulations to:
Eleonora Dehlink, Vienna, Austria who will visit Edda Fiebiger, Children's Hospital Boston, USA to further develop her 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-intenstinal tract? An in-vivo approach.
Daniel P. Potaczek, Cracow, Poland who submitted an application to visit Hideoki Ogawa, Juntendo University School of Medicine, Tokyo where he will develop skills for his project: Genetic variability of alpha chain of high-affinity IgE receptor gene and its expression.
Dahlia Al-Ghoneimy, Cairo, Egypt who will study skin prick testing in the early diagnosis of atopy in infants and children, and the immunotherapeutic modalities. Her Fellowship will be hosted by G. Walter Canonica at DIMI, Genoa, Italy.
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 firstname.lastname@example.org, noting "Free Journal Subscription" in the subject line, with the following details:
City, State/Province and postal code
Name of Member Society
And In Other News （その他のニュース）
Allergy Book Review
Allergy and Asthma in Modern Society: A Scientific Approach
R. Crameri, Editor
List Price: $167.25 USD
Available from: Karger Publishing
Dr David Sutherland, FRACP
Nineways Specialist Clinic, Broadmeadow NSW 2292
The prevalence of allergic diseases and bronchial asthma has increased throughout the industrialized world. This book is a collection of papers which seeks to explore the complex interactions between genetic and environmental factors that may have contributed to this increase. Contributions from a total of 40 authors have allowed a very broad coverage, ranging from epidemiology through to modern advances in molecular biology.
This book was compiled as a tribute to Professor Kurt Blaser, Director of the Swiss Institute of Allergy and Immunology Research, Davos, to celebrate his 65th birthday.
No doubt this book was edited for those with a scientific interest in the etiology and management of bronchial asthma and allergic disease. However, this very scope and the large number of invited authors, means that there would be very few amongst the intended audience that would find all of the topics, ranging from epidemiology through to molecular immunology, equally helpful, or indeed, comprehensible.
This volume is divided into six sections: Introduction, The Environment, The Lung Eosinophils and Asthma, The Skin, Molecular Aspects of Allergy and Asthma, and Immunotherapy. Within this format, there are a total of 18 chapters. The Foreward to the volume is a tribute to Professor Blaser, and it concludes with a brief subject index. It is a slim well-presented volume of 224 pages.
Presumably as the result of the celebratory nature of this book, its contents are extremely varied, and perhaps idiosyncratic. The end result has been an in depth assessment of numerous aspects of asthma and allergic disease, rather than a comprehensive coverage. The scientific quality of the contributions is variable also. Those dealing with epidemiology and basic immunology are of a high quality. A chapter on allergic conjunctivitis includes 22 references. Only four of those references are from 2000 or later publications, and the author's name is included in all but one of the references. Some chapters, such as an examination of the affect of high altitude on bronchial asthma, and the role of sensitization to Malassezia sympodialis in atopic eczema, would be unlikely to warrant a whole chapter in another publication.
Overall, this is a book to be used as a resource, rather than to be read from cover to cover. It would be a valuable addition to institutional libraries, and a useful purchase for clinical immunologists and allergists with wide-ranging scientific interests across the whole field of bronchial asthma and allergy. Others will find significant parts of this volume outside of their own areas of interest.
Find more allergy book reviews on the WAO Website here.