World Medical Journal Reviews
Prof. Richard F. Lockey, MD,
and WAO Web Editor-in-Chief, reviewed premier medical journal articles for
1. BUDESONIDE/FORMOTEROL MAINTENANCE PLUS RELIEVER THERAPY, A NEW STRATEGY
IN PEDIATRIC ASTHMA
(A)Three hundred and forty-one (341) children (4-11 years) with A,
uncontrolled with inhaled corticosteroids (ICS), were included in a 12-month,
double-blind, randomized study to determine whether budesonide/formoterol (B/F) 80/4.5 µg qd maintenance plus prn inhalations versus B/F 80/4.5 µg qd maintenance or budesonide 320 µg qd reduced A exacerbations. The B/F qd plus prn use prolonged the time from first
exacerbation versus fixed dose B (P = 0.02) and fixed dose combination (P<
0.001). Mild exacerbation days and awakenings were significantly lower with
B/F qd plus prn use, and
yearly growth improved by one centimeter versus B 320 µg qd (P< 0.01). B/F used daily plus prn use versus
fixed dose B and fixed dose combination reduces exacerbation rates (both
P<0.001). Editor's comments: Daily use of combination therapy plus prn use may become a new accepted treatment for A. Bisgaard H, et al. Chest 2006; 130: 1733.
randomized controlled trial）によった。その結果、定時吸入プラス増悪時の合剤使用は、合剤の定時吸入あるいはブデソニド高用量使用群に比して、無症状期間の延長などの臨床効果において優れており、また、ブデソニド高用量使用群に比べ、成長抑制効果は年間1cm少なかった。編集者注：一日１回定時吸入プラス増悪時のステロイドLABA合剤使用は喘息治療の新しい戦略になりうる。
2. TYMPANOSTOMY TUBES AND DEVELOPMENTAL OUTCOMES AT 9 TO 11 YEARS OF AGE
Four hundred and twenty-nine (429) children, before 3 years, with persistent
effusion were randomly assigned to undergo the insertion of tympanostomy tubes either promptly or up to nine months
later if effusion persisted. In a previous report, the authors concluded that
prompt versus delayed insertion did not result in improved cognitive
language, speech or psychosocial development at 3, 4 or 6 years. They now
assess literacy, attention, social skills and academic achievement in 391 of
these children at 9 to 11 years and conclude that mean scores of 48
developmental measures in children who underwent early insertion of tympanostomy tubes did not differ significantly from the
scores in the group that was assigned to undergo delayed insertion at the
later age.Editor's comment: The authors suggest that watchful
waiting for at least six additional months with bilateral infusions and for
an additional nine months with unilateral infusions is the preferred
management option in most cases. Recommendations should be individualized.
JL, et al. N
Engl J Med 2007; 356: 248. Editorial, Berman S. N
Engl J Med 2007; 356: 300.
3. MULTIPLE CHEMICAL SENSITIVITIES (MCS): A SYSTEMATIC REVIEW OF
This is a review of provocation studies of persons reporting MCS from a
database search from inception to May 2006. Most studies were insufficiently
controlled. The authors conclude that persons with MCS react to chemical
challenges; however, responses only occur when they can discern differences
between active and sham substances. This suggests that the mechanism of
action is related to expectations and prior beliefs rather than to the
chemical itself. Editor's comment:
Fortunately, humans are not as sensitive to a variety of different
environmental agents as believed by some individuals and physicians. Das-Munshi J, et al. JACI 2006; 118: 1257.
4. LONG-TERM COMPARISON OF 3
CONTROLLER REGIMENS FOR MILD-MODERATE PERSISTENT CHILDHOOD ASTHMA (A) : THE
PEDIATRIC A CONTROLLER TRIAL
This DB 48-week trial of 285 children (6-14 years) with A compared the
efficacy of 3 treatment regimens: fluticasone 100
µg 2x/d (F2X), fluticasone 100 µg/salmeterol 50 µg (FS) in the A.M. and salmeterol 50 µg (S) in the P.M., and montelukast 5 mg (M) in
the P.M. F2X and the FS and S were comparable but the F2X was superior for
clinic-measured FEV1/FVC (P = .015), maximum bronchodilator response (P =
.009), exhaled nitric oxide (P <.001), and methacholine PC20 (P<.001). F2X was superior to M for A control days (64.2% vs. 52.5%;
P = .004) and other control outcomes. Growth over 48 weeks was not
statistically different among groups. The study confirms the current
guideline recommendations favoring inhaled glucocorticoid monotherapy in mild-moderate persistent A. Editor's
comment: Inhaled glucocorticosteroids should be the
primary treatment for mild-moderate persistent childhood A. Sorkness C, et al. J Allergy Clin Immunol 2007; 119: 64.
5. HISTAMINE H4
RECEPTOR (H4R) ANTAGONISTS ARE SUPERIOR TO TRADITIONAL ANTIHISTAMINES IN THE
ATTENUATION OF EXPERIMENTAL PRURITUS
The authors demonstrate that scratching responses in mice, induced by
histamine and selective H4R agonists, were almost completely attenuated in
H4R knockout mice or by pretreatment with a selective H4R antagonist, JNJ
7777120. Pruritus induced by allergic mechanisms
was also inhibited by the H4R antagonist or in H4R knockout mice. The
inhibitory effect of JNJ7777120 was greater than with a histamine H1 receptor
antagonist. The H4R pruritus was shown to be
independent of mast cells or other hematopoietic cells and may result from actions on peripheral neurons. The authors conclude
that the H4R is involved in pruritic responses in
mice more so than the histamine H1 receptor. Editor's comment: Will this new agent provide an alternative and
effective therapy for chronic pruritus? I hope so. Dunford PJ, et al. J Allergy Clin Immunol 2007; 119: 176.
6. IMPACT OF
SALMETEROL/FLUTICASONE PROPIONATE VERSUS SALMETEROL ON EXACERBATION IN SEVERE
After a 4-week, run-in period, 994 clinically stable patients were randomized
to one of two treatment groups, 507 received the salmeterol/fluticasone combination 50/500 µg 2x/d (SFC) and 487 received salmeterol 50 µg 2x/d (S) for 44 weeks. There were 334 exacerbations in the SFC and 464
in the S (P <0.0001). The annualized rate of moderate and severe
exacerbations per patient was 0.92 in the SFC and 1.4 in the S group (35%
decrease). Mean time to first exacerbation in SFC was significantly longer versus
S (128 vs. 93 d, p<0.0001). QOL, PEF and use of rescue medication were
significantly improved in the SFC group. The authors conclude that SFC is
better than monotherapy with S for severe COPD. Editor's comment: SFC reduces exacerbation
frequency in high risk patients with severe COPD. Kardos P, et al. Am J Respir Crit Care Med 2007; 175: 144.
7. ANTIBIOTIC (AB)
TREATMENT OF EXACERBATIONS OF COPD; A RANDOMIZED, CONTROLLED TRIAL COMPARING
PROCALCITONIN (P)-GUIDANCE WITH STANDARD THERAPY
Serum levels of P increase rapidly in the presence of infection. Two hundred
and eight (208) consecutive COPD patients requiring hospitalization for COPD
exacerbation were randomized to P-guided or standard AB therapy. Those
receiving P-guided therapy were treated with AB according to serum P levels;
standard-therapy patients received AB according to the attending physician.
The primary outcome was the AB exposure at the index exacerbation and
subsequent AB requirements for COPD exacerbation within six months. Secondary
outcomes were clinical recovery, symptom scores, length of hospitalization,
need for ICU stay, death, lung function, exacerbate rate, and time to the
next exacerbation. P-guidance reduced AB prescriptions (P< 0.0001), AB
exposure (RR, 0.56; 95% CI, 0.43 to 0.73; P <0.0001), and permitted
significant reduction in total AB exposure for up to 6 months (RR, 0.76; 95%
CI, 0.64 to 0.92; P = 0.004). Outcomes at 14 days to 6 months did not differ,
neither did the exacerbation rate, re-hospitalization rate or the mean time
to next exacerbation. The authors conclude that P-guidance reduces AB use for
up to 6 months with a number-needed-to-treat of 3. Editor's comment: P levels seem to indicate
whether AB will or will not benefit patients with a COPD exacerbation. Stolz D, et al. Chest 2007; 131: 9.
8. FEATURES OF SEVERE
ASTHMA IN SCHOOL-AGE CHILDREN: ATOPY AND INCREASED EXHALED NITRIC OXIDE
This study identified features of severe versus mild-to-moderate asthma in
school children by assessing lung function, presence of atopy and airway
inflammation. A total of 75 children with asthma had lung volume testing, methacholine challenge, allergy evaluation and offline
measures of exhaled nitric oxide (FENO). The severe asthma sub-group (N=39)
required high doses of inhalational corticosteroids (ICS). These 39 children
had more symptoms, greater airway obstruction, more gas trapping, increased methacholine sensitivity, higher concentrations of FENO,
and greater sensitization to aeroallergens. Both the reduction of FEV1 and
increased FENO persisted in the severe versus mild-to-moderate group
throughout the study. Despite adjustments in ICS, the number of exacerbations
was significantly higher in subjects with severe (83%) versus the
mild-to-moderate group (43%). Editor's
comment: Repeated exacerbations, greater allergen sensitization, increased
airflow obstruction, and increased FENO all characterized more severe asthma
in children. Fitzpatrick AM, et al. JACI 2006;118:1218.
9. EGG (E) ORAL
IMMUNOTHERAPY (OIT) IN NONANAPHYLACTIC CHILDREN WITH E ALLERGY
E allergic subjects (positive ingestion hx. within
6 months of beginning the study with a + serum CAP of 7 kU/L
or greater (2 kU/L or greater for subjects =2
years) or with a + allergic reaction to E within 6 months of beginning the
study without a history of anaphylaxis to E underwent a 24-month E OIT
involving modified rush, build-up and maintenance phases. DBPC food
challenges were performed at study conclusion and E-specific IgE and IgG concentrations
measured. E-specific IgG increased significantly,
whereas E-specific IgE did not change in the seven
subjects who completed the protocol. All tolerated significantly more E
protein than at study onset. Two subjects demonstrated oral tolerance. The
authors conclude that allergen-specific OIT to protect subjects with food
allergy may represent a significant advancement in treatment. Editor's comment: Double-blind control studies
with placebo and E oral therapy are now necessary. Buchanan
AD, et al. J Allergy Clin Immunol 2007; 119: 199.
MEASUREMENTS OF MITE AND PET ALLERGEN LEVELS IN HOUSE DUST OVER A TIME PERIOD
OF 8 YEARS
The authors investigated the variability of house dust mites (Der p 1, Der f 1) and cat (Fel d 1) allergens in Dutch homes. Mite allergen
concentrations for the child's mattress, the parents' mattress and the living
room floor were moderately correlated between time-points. Agreement was
better for cat vs. mite allergens. They conclude that over a period of 4
years, mite and cat allergens measured in house dust are sufficiently stable
to use single measurements with confidence in epidemiologic studies. The
within home variance was larger when samples were taken 8 years apart, so
that over a longer period, repetition sampling is recommended. Editor's comment: Dust mite and pet allergen
levels in homes vary little for at least 4 years. Antens CJM, et al. Clin Exp Allergy 2006; 36: 1525.
PHARMACOLOGY OF THE H1 ANTIHISTAMINES
This supplement begins with a review of the discovery of histamine and
antihistamines. It contains chapters on comparative pharmacology, effects on
the cardiovascular system, the central nervous system and their interactions.
It concludes with a section on H1 antihistamines and their effects on
psychomotor performance and driving. Editor's
comment: A complete and excellent review of this subject.
del Cuvillo A, et al. J
Investig Allergol Clin Immunol 2006; 16: Supplement 1.
WAO Now: What's New in the World of WAO
World Allergy Forum Held at the 2007 AAAAI Annual Scientific Meeting, San Diego, CA, USA, 26 February 2007
"A Global Perspective on Genetics, the Environment and Allergy"
Our international expert faculty was chaired by Thomas A.E. Platts-Mills and Michael A. Kaliner, and provided a worldwide update on genetics, the environment and allergy to almost 300 attendees. The first speaker, Adnan Custovic (United Kingdom), discussed whether or not early exposure to allergen is protective, and the presentation by Robert F. Lemanske Jr. (United States) focused on the environment's influence on genetic responses. The successful symposium was concluded by Erika Von Mutius (Germany), who discussed environmental intervention in the management of allergic diseases.
Presenter slides and audio recordings will soon be available for download on the WAF web page.
先月開催された米国アレルギー学会においてWAO共催のWorld Allergy Forumが開催された。全てのスライドが上記ウェブからダウンロードすることができる。
World Allergy Forum is funded through an unrestricted educational grant from
Updated GLORIA Module Now Available
An updated version of GLORIA Module 2: Allergic Conjunctivitis, authored by Prof. Connie H. Katelaris and Dr. Allen P. Kaplan, is now available for downloading on the US GLORIA web site
2007 April GLORIA Placements
V European Asthma Congress and I World Congress on COPD
21-24 April 2007
International GLORIA Faculty:
Allen P. Kaplan
Module 5: The Symptoms and Treatment of Asthma
Module 7: Agioedema
Romanian National Congress of Allergy and Clinical Immunology
26-27 April 2007
Tirgu Mures, Romania
International GLORIA Faculty:
Module 1: Allergic Rhinitis
Module 4: Immunotherapy
GLORIA is supported through unrestricted educational grants from:
New Interactive Case Review
Take a moment to test your knowledge with the new Interactive Case Review based on a Clinical Case Report published in the ACII-JWAO - Trouble in Your Own Backyard: Case Report and Review of Imported Fire Ant Sensitivity. Link
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
Application forms may be downloaded here: Link
*Allergen characterization and standardization
*Clinical and basic studies in allergy and asthma
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.
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
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:
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And In Other News
Allergy Book Reviews
今月の書籍紹介は微生物と免疫に関する本とCollegium Internationale Allergologicumの記録集の２冊である。前者は臨床医から学生まで広く対象となりうるが、後者は最先端の研究者の短い研究報告集であり対象は研究者に限られる。としている。
Microbial Subversion of Immunity: Current Topics
Editors: Peter J. Lachmann, M.B.A. Oldstone
ISBN #: 1904455050
List price: $230.00 USD
Available from: Caister Academic Press
Reviewer: Gary Hellermann PhD
University of South Florida, Tampa, Florida
This is a collection of nine reviews focusing on the strategies used by bacteria, viruses and parasites to avoid detection or destruction by the host's immune system. It begins with an overview of the subversion process and its effects on complement, natural killer cells and other parts of the mucosal innate immune system. This is followed by general reviews of the subversive techniques of viruses, bacteria and helminths. Lastly, there are three papers dealing more specifically with the humoral immune response and dendritic cell reaction to viruses, and a description of the measles virus serving as a model for the mechanisms of inhibition of human antiviral defenses.
The editors point out that all human pathogens by definition have achieved some degree of success in blocking attacks by the immune system and that this review of their methods 'on the battleground' should yield valuable insights into the workings of the immune system. Considering that humans are under constant threat by these highly adaptive organisms, this book fills an important need by bringing together the current findings on microbial subversion of the immune system. The difficulty of the task is matched by the high level of expertise of the contributing authors.
The book's subject, how some viruses, bacteria and parasites manage to avoid our immune defenses, is one of interest to a wide audience teachers, students, researchers and clinicians. The language and concepts are not dauntingly technical, and the current findings are brought out within a logical framework that makes them easy to understand. The contributors to the work all seem to be highly competent and knowledgeable.
While the book's main emphasis is on the various ways that microbes circumvent the innate immune response, there is an excellent review chapter on the innate immune system itself that highlights the host's defense mechanisms and sets the stage for a better understanding of microbial subversion.
The authors of the reviews have done an excellent job combing the literature for the latest information and condensing and summarizing it into a comprehensive report on the state of knowledge about microbial evasion of the human immune system. Each review has an extensive bibliography providing a complete cross section of the current literature.
Chapter 4 on Viral Immune Evasion is especially well written, comprehensive and illustrated with numerous figures showing the pathways blocked by specific viruses. The chapter on immune system subversion by helminths at 70 pages (35 pages of references!) may well be the definitive work on this subject.
Together with chapters on viral inhibition of the humoral immune response, viral effects on dendritic cells and a detailed discussion of the measles virus, the book affords a virtually complete overview of the current research findings. These recent advances in virology demonstrate the great variety of mechanisms employed by these consummate pathogens, and this improved knowledge should provide us with insights to design better vaccines and antiviral drugs.
The subjects are covered in good detail and with competent explanations, but the text seems to suffer in places from a lack of editing that could have improved the clarity and readability.
After reading this book, one comes away with a new appreciation of the value of a healthy and well prepared immune system. The immunocompromized individual is at far greater risk of infection and may even die as a result of an illness that would otherwise be just an inconvenience. By gathering together and evaluating the latest research in this important area of immunology, the authors and editors deserve much credit for producing a work that should be the reference standard in the field for some time.
From Genes to Phenotypes - The Basis of Future Allergy Management
Proceedings of the 25th Symposium of the Collegium Internationale Allergologicum (Supplement 2, 2005 of Allergy & Clinical Immunology International - Journal of the World Allergy Organization)
Editors: H. Løwenstein, J.B. Bienenstock, J. Ring
List Price: $64.95 USD
Available from: Hogrefe & Huber
Reviewer: John B. Ziegler, MB BS, FRACP, MD, DipHEd, FAAAAI
Head, Department of Immunology & Infectious Diseases
Sydney Children's Hospital, RANDWICK NSW, Australia
The Collegium Internationale Allergologicum holds biennial meetings and invites about 200 allergy investigators for an informal gathering to discuss recent allergy research and future therapeutic options. This hard cover volume of 252 pages collects papers presented at the 2004 meeting held in Denmark, covering topics such as gene-environment interaction, T cell regulation, basic mechanisms of effector cell function, mast cells, psychoneuroallergology, asthma, food allergy, eczema, drug reactions, diagnostics and progress in pharmacotherapy, as well as nonspecific and specific immunotherapy.
The stated purpose, implied by the title, is to bridge the gap between genetics and mechanisms of allergic responses and office allergy practice. Evolving from the proceedings of a conference, however, the content is clearly determined by the interests and research programs of the participants with no clear themes emerging. The purpose is perhaps better described to allow allergy research groups to present recent findings and interests. The book does not present discussion of genotype-phenotype correlations, which the title seems to promise, but of course, none could really be expected for allergic diseases, which appear to be multigenic disorders.
This is not a reader-centered book. It does not provide a revue of any broad areas of allergy research, theory or practice. It does not describe current knowledge about genetic factors leading to allergic phenotypes. It does not describe allergic phenotypes. Its audience is not students, trainees or physicians in other disciplines seeking an update on current thinking. Rather, its audience is academic allergists, researchers working in allergy and practicing allergists and immunologists seeking a window on current research trends.
The book comprises about 70 papers of about 3-4 pages mostly presented in the format of journal articles with abstracts, methods, results, discussion and a short reference list. Some are short reviews presenting published work, though even this type of paper generally has fewer than 20 references. Unusual for a bound volume, it does not have a subject index. There is an author list and an index based on keywords (which are not necessarily standard terms) provided by authors. This has some unusual effects. An Australian contribution on latex immunotherapy is indexed under "latex allergy," "basophils," and "Hev b 6.01" but not "immunotherapy." Many of the terms are abbreviated names, for example, of cell surface molecules. Although its role is of great interest, few readers would search for IRp60 (a recently described inhibitory receptor on mast cells).
This book, published in 2006, presents papers presented in August 2004, so the reader does not benefit from the immediacy afforded to the delegates. The content is largely in the form of short scientific papers but is apparently not peer reviewed. In fact, there is usually insufficient methodological detail to allow critical appraisal. This, at first glance may be a weakness, but it is also a strength since it affords the opportunity, for example, to publish methods which, though not necessarily new technology, are novel approaches to problems in allergy research (basophil histamine release assay to detect circulating dietary allergens; CD63 expression as a marker for basophil activation). It allows for short reviews to encourage readers to enquire further into emerging areas (epitope diversity as a correlate of severity of food allergic reactions). It provides an opportunity to put forward hypotheses which remain largely untested but may prove to be very important (antibodies against membrane bound IgE spacer sequences to modulate IgE synthesis). All those wishing to keep abreast of current thinking in allergy will enjoy thumbing through this book. Many might prefer to spend that time on recent issues of peer-reviewed journals.
Find more allergy book reviews on the WAO Website here.