Medical Journal Reviews
Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, reviewed premier medical journal articles for practicing allergists. 南フロリダ大学ロッキー教授による実地医家向けの医学雑誌レビュー
1. INVARIANT NATURAL KILLER T CELLS (NK) IN ASTHMA (A) AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
These authors studied the frequency of NK in the airways of subjects with mild (8 not treated with inhaled corticosteroids) and moderate (16 treated with inhaled corticosteroids) A, 10 subjects with COPD and 10 controls. NK were enumerated with flow cytometry with the use of CD1d tetramers loaded with α-galactosylceramide and antibodies specific to the NK receptor in samples of BAL, induced sputum, and bronchial-biopsy specimens. Real-time PCR analysis was performed on bronchoalveolar-lavage cells for evidence of gene expression of the NK receptor. The authors found that fewer than 2% of the T cells obtained from all subjects were similar and no expression of messenger RNA for the NK-receptor domains Vα24 and Vβ11 were present. NK are found in low numbers in the airways of subjects with asthma, COPD, and controls. Editor’s comment: More studies are needed to determine a possible role for NK in asthma. Vijayanand P, et al. N Engl J Med 2007; 356: 1410. Editorial, Ho LP: 1466.
2006年4月のWAO News & Notesにて、N Engl J Med 2006; 354: 1117.を紹介し、「Akbariらは喘息患者の気管支洗浄液や肺生検試料をもちいて肺に存在するCD3+CD4+T細胞のうち約60%がこのNKT細胞であることを見いだした。正常試料（T細胞の浸潤はほとんどない）やサルコイドーシス患者肺試料で同様にNKT細
ことは記憶に新しい。今回は別なグループが同様な手法をもちいて調査したところ、再現性は得られず、喘息患者においてさえも、NKT細胞の割合はT細胞の2%以下であったとしている。このdiscrepancyに関しては、著者およびNEJMの編集者はNKT細胞に特異的な抗体をもちいる際に十分なブロッキング抗体を使用していなかったと推測している。訳者注：ブロッキング抗体の適切な使用は初歩的な技術であり、もし本当にそうであればこのようなことを見逃したNEJM編集担当者の責任は大きいのではないか。サルコイドーシス患者ではAkbariらもNKTの増加は認めていないが、ブロッキング抗体ではこの説明もつかない。訳者が2006年4月のWAO News & Notes日本語版で記載した批判的なコメントを以下に引用させていただく。「訳者注：従来の報告では喘息患者において増加しているIL-4とIL-13を産生するCD3+CD4+細胞はTh2細胞であると考えられていた。そしてTh2細胞はダニなどの抗原に特異的に反応して活性化されると想像されていた。今回の発表は喘息病態として最も本質的な概念を覆すものでまさに世紀の発見といえる。しかし、もし環境中や生体内に存在することが予測される未発見のNKT活性物質により非特異的に多くのNKT細胞が活性化された場合、大量のIL-4やIL-13が分泌されるのでIgE抗体が異常に増加するはずである。だが、この論文に記載されている症例のうち、数例はIgE抗体が低値の非アレルギー性喘息のようにみえる。そのような症例では肺にNKT細
2. OPIATE THERAPY IN CHRONIC COUGH (CC)
27 patients with CC enrolled into a randomized DBPC study using four weeks of slow-release morphine sulfate (MS) 5 mg 2X/day and a corresponding period of matched placebo. An open-labeled extension of the core study allowed dose escalation to MS 10 mg 2X/day. CC was assessed using the Leicester Cough Questionnaire (LCQ), daily symptom diary and citric acid cough challenge (CACC). A significant improvement of 3.2 points over baseline was noted on the LCQ (p < 0.01). A rapid reduction of 40% in CC scores was noted in subjects on slow-release MS ( p < 0.01). CACC test results did not show any significant changes. Two-thirds of the 18 patients in the extension study opted to increase the MS to 10 mg 2X/day, and at the end of three mo, there was a similar improvement in CC between the 5- and 10-mg groups. MS is an effective antitussive in CC at doses of 5 to 10 mg twice daily. Editor’s comment: The risk (side-effects, dependence and sedation) – benefits (decreased cough) have to be weighed when prescribing MS for CC. Morice AH, et al. Am J Respir Crit Care Med 2007; 175: 312.
3. OVERWEIGHT, OBESITY, AND INCIDENT ASTHMA–A META-ANALYSIS OF PROSPECTIVE EPIDEMIOLOGIC STUDIES
This is an online bibliographic database search for studies evaluating body mass index (BMI) and incident asthma in adults. Independent observers extracted data from studies meeting predetermined criteria [defined categories of normal weight (BMI < 25), overweight (BMI, 25-29.9), and obesity (BMI ≥ 30)]. Seven studies of 333,102 subjects met inclusion criteria. Overweight and obesity conferred increased odds of incident asthma, with an OR of 1.51 (95% CI, 1.27 – 1.80). A dose-response effect was observed. The observations were present in both men (OR, 1.46; 95% CI, 1.05 – 2.02) and women (OR, 1.68; 95% CI, 1.45 – 1.94; p = 0.232 for the comparison). The authors conclude that overweight and obesity are a dose-dependent risk in the odds of incident asthma. Editor’s comment: This is the best review available indicating that overweight and obesity are risk factors for asthma. Beuther DA, et al. Am J Resp Crit Care Med 2007; 175: 661.
4. SAFETY OF ANTI-IMMUNOGLOBULIN E THERAPY WITH OMALIZUMAB (O) IN ALLERGIC PATIENTS AT RISK OF GEOHELMINTH INFECTION (GI)
137 subjects (12 -30 years) at high risk of GI were included in a randomized DBPC trial. All received pre-study anthelminthic treatment followed by 52 weeks’ treatment with O or placebo (P). 50% (34/68) of the O subjects experienced at least one intestinal GI vs. 41% (28/69) of P subjects [OR 1.47, 95% CI 0.74 – 2.95, one-sided p = 0.14; OR (adjusted for study visit, baseline infection status, gender and age) 2.2 (0.94 – 5.15); one-sided p = 0.035], providing some evidence for a potential increased incidence of this form of infection in subjects on this medication. Infection severity and response to anthelminthics appeared to be unaffected by O therapy. The authors conclude in this exploratory study that O therapy may be associated with a modest increase in the incidence of GI. However, such therapy was safe and well tolerated. Editor’s comment: More information is needed to determine whether anti-IgE therapy is associated with an increased risk of intestinal helminth infections. Cruz AA, et al. Clin Exp Allergy 2007; 37: 197.
5. SHORT-COURSE MONTELUKAST (M) FOR INTERMITTENT ASTHMA (IA) IN CHILDREN–A RANDOMIZED CONTROLLED TRIAL
220 children (aged 2 – 14 yr) with IA were randomized in this multicenter, DBPC clinical trial over 12 months, 107 to M and 113 to placebo (P), to determine whether a short course of M in children with IA would modify the severity of an asthma episode. There were 681 treated episodes (345 M, 336 P) provided by 202 patients. The M group had 163 unscheduled health care resource utilizations for A compared with 228 in the P group (OR, 0.65; 95% CI, 0.47 – 0.89). There was a nonsignificant reduction in specialist attendances and hospitalizations, duration of episode, and ß-agonist and prednisolone use. Symptoms were reduced by 14% and nights awakened by 8.6% (p = 0.043), days off from school or childcare by 37% and parent time off from work by 33% (p < 0.0001 for both). The authors conclude that M introduced at the first signs of an A episode results in a modest reduction in acute health care resource utilization, symptoms, time off from school, and parental time off from work in children with IA. Editor’s comment: More studies are necessary to determine the effects of M on viral respiratory tract infections, particularly when M is used to prevent viral infections. Robertson CF, et al. Am J Respir Crit Care Med 2007; 175: 323.
6. PREVALENCE OF VIRAL RESPIRATORY TRACT INFECTIONS IN CHILDREN WITH ASTHMA (A)
Respiratory specimens from children aged 2 to 17 years with A exacerbations (case patients, n = 65) and with well-controlled A (control subjects, n = 77), frequency matched by age and season of enrollment, were tested for rhinoviruses, enteroviruses, respiratory syncytial virus, human metapneumovirus, coronaviruses 229E and OC43, parainfluenza viruses 1 to 3, influenza viruses, adenoviruses, and human bocavirus. Respiratory viruses were associated with A exacerbations (63.1% in case patients vs. 23.4% in control subjects; OR, 5.6; 95% CI, 2.7 – 11.6). Rhinoviruses were the most prevalent viruses (60% among case patients vs. 18.2% among control subjects) and the only ones significantly associated with exacerbations (OR, 6.8; 95% CI, 3.2 – 14.5). The authors conclude that rhinoviruses should be a target for therapies as a means to decrease asthma exacerbations. Editor’s comment: This article confirms that rhinoviruses are the most important viruses associated with asthma exacerbations in children. Khetsuriani N, et al. JACI 2007; 119: 31.
7. CORRELATION BETWEEN BRONCHODILATOR RESPONSIVENESS AND QUALITY OF LIFE (QOL) IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
63 subjects with COPD, mean age 71.7 yr, were investigated to determine the relationship between reversibility and QOL. Post-bronchodilator FEV1, % predicted, was positively correlated with both the total scores of 2 different QOL questionnaires (p < .0001 and p < 0.006). For the most part, reversibility of FVC was also positively correlated. The reversibility of FEV1 was neither correlated with the total score nor any other items in the scales. The authors conclude that patients who have a FVC that respond to a bronchodilator at rest might result in improvement of QOL after Rx. Editor’s comment: Bronchodilators probably improve the QOL in patients with COPD primarily because of increased respiratory function. Omata M, et al. Allergol Internatinal 2007; 56: 15.
8. ASYMMETRIC T LYMPHOCYTE DIVISION IN THE INITIATION OF ADAPTIVE IMMUNE RESPONSES
Reviewed by Gary Hellermann, Ph.D.
T cell activation through interaction with MHC-peptide at the immunological synapse is the key feature of adaptive immunity, but it is only part of the picture. Activation also produces memory T cells that generate a rapid response when faced with the same antigen. In this intriguing article, the authors hypothesize that polarization of specific proteins between the synapse and the opposite pole in T cells during prolonged contact with antigen-presenting cells results in an asymmetric cell division producing two daughter cells--one an effector T cell bearing markers from the synapse side and the other a memory T cell with markers from the distal pole. Editor’s comment: The reason for the extended interaction between T cells and antigen-loaded dendritic cells appears to be co-generation of effector and memory T cells by asymmetric cell division. Chang JT et al. Science 2007, 315:1687. Editorial, Littman DR, et al.: 1673.
9. A POOLED ANALYSIS OF FEV1 DECLINE IN COPD PATIENTS RANDOMIZED TO INHALED CORTICOSTEROIDS (ICS) OR PLACEBO (P)
This is a pooled study of patient-level data from seven long-term randomized controlled trials of ICSs vs. P lasting ≥ 12 mo in patients with moderate-to-severe COPD. 3,911 randomized participants (29.2% female) were included in the analysis. In the first six mo after randomization, ICS use was associated with a significant mean (± SE) relative increase in FEV1 of 2.42 ± 0.19% compared with P (p < 0.01). However, from 6 to 36 months, there was no significant difference between P and ICS therapy in terms of FEV1 decline (-0.01 ± 0.09%; p = 0.86). The authors conclude that ICS therapy is more effective in ex-smokers than in current smokers with COPD and that women have larger responses to ICS than men. However, this effect only lasts for approximately six months, and thereafter, does not modify the decline in FEV1. Editor’s comment: Is it possible there are phenotypes within this cohort with reversible airways disease that responds better and over a longer period than others who have minimal or no reversibility? Soriano JB, et al. Chest 2007; 131: 682.
10. EVIDENCE-BASED SELECTION OF INHALED CORTICOSTEROID (ICS) FOR TREATMENT OF CHRONIC ASTHMA
This is an excellent evidence-based article on the published literature comparing various ICSs. There is considerable heterogeneity in the published results on these medications and their efficacy, and side-effects depend on their formulation, dosing, device used, and the subjects’ age, severity of asthma, and inhaler technique. Each medication is reviewed and the pros and cons of using it elaborated upon. The article is 12 pages with 137 citations. Editor’s comment: This is a nice review on a subject of importance to every physician who treats asthma. Abdullah AK, et al. J Asthma 2007; 44: 1
11. UPDATE IN ASTHMA 2006
Drs. Moore and Peters update asthma 2006. New concepts discussed include long-acting beta-agonists, risk, and the genetics of the β2-adrenergic receptor. They also review the pros and cons of whether early inhalational corticosteroids prevent development of asthma in transient wheezing infants. Anti-tumor necrosis factor-α is discussed as a potential new asthma medication. In addition, gene-environment interactions, pharmacogenomics, endotoxin and ozone, remodeling in asthma (vascular remodeling and remodeling in children), and ADAM33, the gene that best exemplifies the increasing significance of extracellular matrix proteins and mesenchymal cells in asthma pathogenesis, are discussed. Editor’s comment: Great review for physicians who care for patients with asthma. Moore W et al. Am J Resp Crit Care Med 2007; 175: 649.
WAO Now: What's New in the World of WAO
New Synopsis Available
A new synopsis on Pharmacotherapy for Allergic Diseases has been posted on the WAO Web site. Authored by Dr. Saha Siddiqui, Prof. Peter Bradding, and Prof, Stephen Holgate from the UK, this synopsis reviews currently available therapies for the treatment of allergic diseases, explaining their mechanisms of action, major side effects, and general comments about their use. To read the synopsis, click here.
WAO's Allergen Specific Immunotherapy Document
The World Allergy Organization (WAO) convened a group of experts to provide guidelines for the methodology of future immunotherapy studies to ensure that patients are treated based on sound scientific evidence and to minimize the risk of misusing limited financial resources for scientific studies. The document summarizes the recommendations for study design, patients’ selection, appropriate outcomes and statistical treatment to be used in planning and performing clinical trials with specific immunotherapy.
The document was recently published in the March 2007 Issue of Allergy: European Journal of Allergy and Clinical Immunology and is now available to you free from PubMed.
You may also access the document from WAO’s Allergic Disease Resource Center.
New Interactive Case Review
Take a moment to test your knowledge with the new Interactive Case Review based on a Clinical Case Report - ACE Induced Angioedema by Dr. Byol Shin.
Call for Applications
WAO Short-Term Research Fellowship 2007 Applications
The World Allergy Organization (WAO) offers three Short-Term Research Fellowships, to commence in the latter half of 2007, to support junior allergists to visit a center of their choice to learn a research technique. The expected duration of each attachment is 2-3 weeks. WAO will contribute up to a maximum of $2,500 USD, to include travel and accommodations, for each Short-Term Fellowship.
Priority will be given to junior clinicians within five years of award of the most recent professional degree, who are specializing in allergy and who are affiliated to an academic department or clinical institute. Applicants must be current members of a WAO member society.
The Short-Term Fellowships will be applied to a project which meets one of the WAO Research Priorities:
- Genetic factors involved in the development of allergic disease and response to treatment
- Allergen characterization and standardization
- Clinical and basic studies in allergy and asthma
Application forms may be downloaded here
Applications must be received by WAO head office not later than 31 May 2007
The WAO Henning Løwenstein Research Award 2007
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.
WAO Henning Løwenstein賞、賞金は2万ユーロ（３００万円強）。
The winner will receive EURO 20,000 together with a travel grant to attend the World Allergy Congress.
For application guidelines, visit www.alk.abello.com and click on "The WAO Henning Løwenstein Research Award."
Deadline: 30 June 2007
World Allergy Congress (WAC) Travel Grants
WAO, in partnership with Schering-Plough Corporation (SPC), the European Academy of Allergology and Clinical Immunology (EAACI), and the American Academy of Allergy, Asthma and Immunology (AAAAI), is sponsoring several Travel Grants for young scientists to attend WAO’s World Allergy Congress (WAC) in Bangkok, Thailand, 2-6 December 2007. For further information, click here.
You are invited to attend…
WAF Symposium: Immune Tolerance
XXVI EAACI Congress
Tuesday, 12 June 2007, 8:30 - 10:00
Göteborg Convention Centre, Room K2-K3
Michael A. Kaliner, United States
Anthony J. Frew, United Kingdom
Concepts in tolerance induction in the lung
Dale Umetsu, United States
Modulation of IgE-related diseases in children: atopic asthma as a paradigm
Patrick Holt, Australia
Can omalizumab synergize immunotherapy?
Thomas Casale, United States
World Allergy Forum is supported through an unrestricted educational grant from
2007 World Allergy Congress Symposium: Masqueraders of Allergic Disease
XXVI EAACI Congress
Tuesday, 12 June 2007, 15:30 – 17:00
Göteborg Convention Centre, Room K2-K3
Chair: Michael A. Kaliner, United States
Connie Katelaris, Australia
Ronald Dahl, Denmark
Michael A. Kaliner, United States
June Educational Program Placements
The Asthma and Allergy Society of Virginia
16-17 June 2007
Virginia Beach, Virginia
US GLORIA Faculty:
Module 5: Treatment of Severe Asthma
Louisiana Society of Allergy, Asthma & Immunology
23-24 June 2007
New Orleans, Louisiana
US GLORIA Faculty:
Module 2: Allergic Conjunctivitis
Module 5: Treatment of Severe Asthma
GLORIA is supported through unrestricted educational grants from:
GLORIA Module 5: Treatment of Severe Asthma Now Available!
WAO is excited to announce the completion of the Treatment of Severe Asthma Module, with is now available for download.
Seminars & Conferences Placement
Mexican National Congress on Clinical Immunology and Allergy
27-30 June 2007
WAO Invited Lecturer:
Emerging Societies Meeting - Cancun, Mexico
WAO's first Emerging Societies Meeting (ESM) of 2007 will take place during the LXI National Congress of Clinical Immunology and Allergy, 27-30 June 2007 in Cancun, Mexico. The ESM is intended as a follow-up to the ESM that was held in Latin America in 2006 and will include representatives from Honduras, Guatemala, Cuba, El Salvador, Nicaragua and Martinique. This meeting is jointly funded by the American College of Allergy, Asthma and Immunology, the Mexican College of Allergy, Asthma and Clinical Immunology and the World Allergy Organization.
For more information on the Mexican College of Allergy, Asthma and Clinical Immunology’s meeting 27-30 June 2007, please click here.
Sign up for Online Journal Subscription -
WAO and Hogrefe & Huber Publishers are offering a limited number of free online 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, online subscription, please send an e-mail to email@example.com, noting "Free Journal Subscription" in the subject line, with the following details:
Last (Family) name
City, State/Province and postal code
Name of Member Society
And In Other News
Two Allergy Book Reviews
Bronchial Asthma: A Guide for Practical Understanding and Treatment
Edited by: M Eric Gershwin, MD and Timothy E Albertson, MD, MPH, PhD.
List price: $125.00 USD (hardcover and eBook)
$99.50 USD (paperback)
Available from: Humana Press
Dr David C Sutherland, FRACP
Nineways Specialist Clinic, Broadmeadow, NSW, Australia
This is the 5th edition of a comprehensive guide to the diagnosis and management of bronchial asthma. Previous editions have been well reviewed in the medical press. The current edition provides an update of recent developments and relatively new drug therapy, along with a greater use of tables and charts, which are deemed to make the book more "user friendly". The coverage of the topic is encyclopaedic, with each chapter, and indeed sections within chapters, written so that they will stand alone. This is both the strength and the weakness of this volume.
The textbook is designed to provide rapid access to practical information regarding the diagnosis and management of bronchial asthma, gleaned from an enormous number of scientific studies and reviews, published over the last thirty years.
This volume is designed to provide practical information for generalists, and for specialists other than chest physicians and allergists/immunologists, as at least all clinicians will be required to manage this common condition, as part of the total care of their patients.
The scope of the book is very comprehensive, ranging from basic immunology and pulmonary physiology, through management issues and specific clinical problems, to lifestyle issues. The format of the book allows rapid access to information, through the use of “key points”, numerous tables and figures, and summaries. Most of the chapters provide comprehensive, and up-to-date lists of references.
This volume succeeds in its aim of providing practical, readily accessible, information about the diagnosis and management of bronchial asthma for those without a specialist interest in the area. However, this format means that the volume is not designed to be read from cover to cover, and even within single chapters, there is a great deal of repetition. This format does allow for the inclusion of a great deal of detailed information which may be of interest to individual clinicians, or perhaps relevant to the management of specific patients, but not necessarily of interest to the general reader. Much of the information (for example epidemiology, drug information, health delivery issues and the management of asthma in "minorities") is directed to the North American audience, and has less relevance to clinicians elsewhere.
Overall, this is a very useful resource text, and should be included in all institutional libraries. The ease of access to detailed information will make it an attractive resource for undergraduate and postgraduate students outside of the areas of respiratory medicine and allergy/immunology.
Oxford Handbook of Clinical Immunology and Allergy
Edited by: Gavin Spickett
List Price: $45.00 USD
Available from: Oxford University Press
Thomas Chacko, MD
Division of Allergy and Immunology
University of South Florida College of Medicine, Tampa, FL, USA
This handy pocket reference is a practical and clinically relevant guide for the diagnosis and management of diseases in clinical immunology and allergy.
It provides the physician and other healthcare professionals with a quick reference and covers a wide range of clinical topics, basic laboratory tests, and the latest advances in the field.
The book is geared toward the novice student, sub-specialty resident in allergy and immunology, and other physicians who want a quick reference book for high yield information.
The pocket handbook is divided into 2 sections. The first section covers clinical diseases, including primary and secondary immunodeficiencies, allergic diseases, autoimmunity, connective tissue diseases, and vasculitis. There are multiple tables within each chapter but few treatment algorithms. Even rare diseases are highlighted with key clinical points. The second section covers diagnostic tests, and summarizes the methodology and pros and cons of each test.
This is an excellent pocket reference for clinical immunology and allergy. The sections are arranged to allow for quick retrieval of key facts. It is small and convenient to carry. Other sources are necessary for a more in depth review of these topics, but this is a good start.
In summary, the Oxford Handbook of Clinical Immunology and Allergy will be particularly helpful to the student or physician who wants a quick convenient resource to retrieve key facts, in a broad range of topics, related to this field.
Find more allergy book reviews on the WAO Website here.