November World Medical Journal Review
Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, reviewed
premier November medical journal articles for practicing allergists.
1. THE NATURAL HISTORY OF ASTHMA IN CHILDREN AND ADULTS BY DRS CHARLES REED & GAIL SHAPIRO
Dr. Reed lists six predictors of persistence and severity of adult asthma to include continued exposure to allergens, including occupational agents, older age onset, aspirin sensitivity, socioeconomic status, smoking and coexisting disease (COPD, bronchiectasis, etc.). For children, both Drs. Reed and Shapiro include a family history of atopy, early sensitization, and airway hyper-responsiveness. Dr. Shapiro also includes early onset; low lung function; female sex; smoking, passive smoking and smoking during pregnancy; and maternal asthma. Dr. Reed, for children, covers more frequent and severe asthma, onset during school age, increased serum IgE, increased URIs, lack of contact with other children, parenting problems and childhood psychological problems. Dr. Shapiro concludes, regardless of the prognosis of childhood wheezing, that parents of children with both low and high risk for persistent disease can be comforted and reassured if they follow an action plan for daily maintenance treatment and for acute exacerbations of asthma. Editor’s comment: Two outstanding articles discuss the vexing problem of who will and who will not have persistent childhood and adult asthma. Reed CE, J Allergy Clin Immunol 2006; 118: 543; the late Dr. Shapiro GG: 562.
2. THE EFFECTS OF A MONOCLONAL ANTIBODY DIRECTED AGAINST TUMOR NECROSIS FACTOR-α IN ASTHMA
Infliximab (I) (Remicade), a recombinant human-murine chimeric monoclonal antibody that specifically and potently binds and neutralizes the soluble TNF-α homotrimer and its membrane-bound precursor, was used in a DBPC, parallel-group study in 38 patients with moderate asthma treated with inhaled corticosteroids who were symptomatic during a run-in-phase. Lung function, symptoms and inhaled β2-agonist usage were monitored. There was no change in morning PEF, however, it was associated with a decrease in mean diurnal variation in PEF at wk 8 (p = 0.02). Likewise there was a decrease in exacerbations in the treatment group (p = 0.01) and an increased probability of freedom from exacerbation with time (p = 0.03). I decreases levels of TNF-α and other cytokines in sputum supernatants. No serious adverse events occurred. Editor’s comment: I looks like a promising therapy for moderate asthma. Erin EM, et al. Am J Respir Crit Care Med 2006; 174: 753.
3. URINE LEUKOTRIENE E4 LEVELS ARE ASSOCIATED WITH DECREASED PULMONARY FUNCTION IN CHILDREN WITH PERSISTENT AIRWAY OBSTRUCTION
This study was designed to assess the relationship between daily variability in urinary leukotriene E4 (LTE4) levels and daily lung function in 50 children with moderate to severe asthma primarily taking an inhaled corticosteroid (ICS) and long-acting β-agonist (LABA). Urinary LTE4, monitoring of FEV1, and albuterol use were measured. Daily variability in LTE4 levels is associated with clinically significant decreases in pulmonary function. In children who demonstrate a response associated with an increase in urinary LTE4 levels, leukotriene receptor antagonists protect against daily FEV1 decreases, which may be greatest in those with persistent airway obstruction despite the use of combined ICS and LABA therapy. Editor’s comment: Asthma is a complex disease and what is good for the goose may not be good for the gander. Rabinovitch N, et al. J Allergy Clin Immunol 2006; 118: 635.
4. THE COMPLEMENT INHIBITOR ECULIZUMAB IN PAROXYSMAL NOCTURNAL
Patients (87) underwent randomization to receive either placebo
(P) or eculizumab (E, a humanized monoclonal antibody against terminal
complement protein C5 that inhibits terminal complement activation)
intravenously. Subjects were given 600 mg weekly for four weeks,
followed one week later by a 900-mg dose and then 900 mg every other
week through week 26. Stabilization of hemoglobin levels in the
absence of transfusions was achieved in 49% of treated vs. P
(P<0.001). During the study, no packed red cells were administered to
the treatment group vs. 10 to the P group (P<0.001). E reduced
intravascular hemolysis vs. P (P<0.001). There was a statistical
improvement in quality of life in the treated group (P<0.001). There
were no serious adverse events considered to be treatment-related.
Editorfs comment: E is an effective therapy for PNH. Hillmen P, et
N Engl J Med 2006; 355: 1233.
5. CONCLUSIONS FROM THREE SEPARATE PAPERS FROM THE EUROPEAN HEALTH
The first study determined cat allergen levels in approximately 3,000
mattresses during home visits in 22 communities. It showed that people
who do not own cats may be exposed to high levels of cat allergen in
their homes, particularly if they live in communities with high cat
ownership. The second article determined that there are large
qualitative and quantitative differences in house dust mite allergen
levels partially explained by geographic and housing characteristics.
They recommend that mite allergen levels could be reduced by replacing
mattresses and increasing ventilation of the bedroom, particularly in
the winter. The third article, perhaps the most interesting, determined
that selective avoidance of cats subsequent to the onset of asthma and
allergy was observed for childhood cat-keeping and adult cat
acquisition, implying that part of the protective effects of childhood
cats on asthma and allergy can be attributed to selective avoidance.
Editorfs comment: Allergen avoidance is complex in spite of the best
intentions of the physician and patient. Heinrich J, et al. J
Allergy Clin Immunol 2006; 118: 674; Zock J, et al: 682; Svanes C,
et al: 691.
Cat allergen level: Its determinants and relationship to specific IgE to
cat across European centers
Distribution and determinants of house dust mite allergens in Europe:
The European Community Respiratory Health Survey II
Do asthma and allergy influence subsequent pet keeping? An analysis of
childhood and adulthood
6. PHARMACOLOGIC AND ANTI-IgE TREATMENT OF ALLERGIC RHINITIS ARIA
UPDATE (IN COLLABORATION WITH GA2LEN)
This document updates the ARIA sections on the pharmacologic and
anti-IgE treatment of allergic rhinitis literature published between
January 2000 and December 2004. Oral H1-antihistamines,
intranasal corticosteroids, intranasal H1-antihistamines,
intranasal chromones, and anti-IgE mab achieved level evidence A, for
seasonal and perennial rhinitis in children and adults. Anti-leukotrienes
achieved an A level for seasonal rhinitis but not for perennial rhinitis
for both groups. For gpersistent rhinitis,h all treatments for both
groups were either A or B except for the intranasal chromones which
could not be rated. Editorfs comment: Physicians have a variety of
different, proven treatments for seasonal and perennial rhinitis.
Bousquet J, et al.
Allergy 2006; 61: 1086.
7. A 10 YEAR ASTHMA PROGRAMME IN FINLAND: MAJOR CHANGE FOR THE
A National Asthma Program was undertaken in Finland from 1994-2004
to improve asthma care and prevent increased costs. Although the
incidence of asthma is increasing, the number of hospital days fell by
54%, mortality decreased, and absolute numbers for disability pensions,
allowances for days off work, and need for rehabilitation all decreased
30 to 50%. Most impressive was that there was an annual reduction in
cost per patient of 50%. The authors conclude that diseases such as
asthma require a multi-disciplinary action program with a broad
commitment by the health care system and society. Editorfs comment:
Optimal care and compliance led to decreased morbidity and mortality
from asthma. Haahtela T, et al.
Thorax 2006; 61: 663.
8. PERSISTENCE, ADHERENCE, AND EFFECTIVENESS OF COMBINATION
THERAPY AMONG ADULT PATIENTS WITH ASTHMA
These authors compared persistence, adherence and effectiveness
between patients with asthma, 16 to 44 yrs, using either a combination
of an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA)
in one inhaler or the individual use of two different inhalers with
similar medications. It is a retrospective 1-to-1 matched cohort of
newly treated asthmatics selected from a database between 1999 and 2002.
Using a variety of statistical models, persistence of use of medication
fell to 10% and 5% after 12 months for combination and concurrent user,
respectively. Combination users were found to be 17% less likely to stop
their treatment, filled on average 0.9 more prescriptions per year, and
were found to be 17% less likely to have a moderate to severe asthma
exacerbation. Editorfs comment: When an ICS and LABA are used in one
inhaler vs. two separate inhalers, compliance and outcomes improve.
Marceau C, et al.
J Allergy Clin Immunol 2006; 118: 574.
9. IMMUNOTHERAPY WITH A RAGWEED-TOLL-LIKE RECEPTOR 9 AGONIST
VACCINE FOR ALLERGIC RHINITIS
These authors conducted a randomized DBPC trial of a vaccine
consisting of Amb a 1, conjugated to a phosphorothioate
oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC) in 25
ragweed allergic subjects. They received six weekly injections of AIC
vs. placebo before the ragweed season. The vaccine did not reduce the
albumin level in nasal-lavage fluid but had positive effects on peak
season rhinitis scores (P=.0006), peak-season daily nasal symptoms
scores (P=0.02), and midseason overall quality-of-life (P=0.05). It also
induced a transient increase in Amb a 1-specific IgG antibody and
suppressed the seasonal increase in Amb a 1-specific IgE antibody. Some
clinical benefits and seasonal specific IgE antibody responses were
observed in the subsequent ragweed season. Editorfs comment: More
studies are needed but AIC may be useful to treat allergic rhinitis.
Creticos PS, et al.
N Engl J Med 2006; 355: 1445.
10. KILLED MYCOBACTERIUM VACCAE SUSPENSION IN CHILDREN WITH
MODERATE-TO-SEVERE ATOPIC DERMATITIS: A RANDOMIZED, DOUBLE-BLIND,
This multi-centered study determined the effects of intradermal
injection of killed M. vaccae (0.1 or 1 mg) on patients, aged
5-16, with moderate to severe AD. The primary end point was change in
severity at 12 weeks using a six area, six sign, atopic dermatitis
score. Secondary end points included changes in disease extent,
patientfs global assessment and childrenfs dermatologic QOL index. In
166 randomized patients, M. vaccae was no more effective than
placebo in ameliorating the severity of AD. Editorfs comment:
Decreased exposure to mycobacterial infection does not seem to be a
reason for the increased incidence of atopic dermatitis. Berth-Jones
J, et al.
Clinical and Experimental Allergy 2006; 36: 1115.
11. PROBIOTICS IN THE PREVENTION OF ANTIBIOTIC-ASSOCIATED DIARRHEA
(AAD) IN CHILDREN: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Six randomized, placebo-controlled trials (766 children) were
included in this meta-analysis to determine whether or not treatment
with probiotics vs. placebo reduced the risk of AAD. The results show
that such treatment reduced the risk of AAD from 28.5% to 11.9% (RR,
0.44, 95% CI 0.25 to 0.77, random effect model). Reduction of risk was
associated with the use of Lactobacillus GG, S. boulardii
or B.lactis & Str. thermophilus. The authors conclude that for
every seven patients that would develop AAD while on antibiotics, one
fewer would occur if they also received probiotics. Editorfs comment:
Give cultured yogurt or probiotics. They decrease AAD in children.
Szajewska H, et al.
J Pediatr 2006; 149: 367.
12. PSYCHIATRIC ADVERSE EFFECTS OF CORTICOSTEROIDS
Two large meta-analyses found that severe reactions occurred from
systemic corticosteroids in nearly 6% of patients and mild to moderate
reactions in about 28%. Side effects include mood, cognition, sleep and
behavior problems (frank delirium or even psychosis). The most common
are euphoria and hypomania. Dosage seems to be most related to the
incidence of adverse effects. In severe cases, where these drugs cannot
be reduced, antipsychotics or mood stabilizers may be required.
Editorfs comment: An excellent review of a problem that
allergists/immunologists face all the time. Warrington TP, Bostwick
Mayo Clin Proc 2006; 81: 1361.
WAO Now: What's New in the World of WAO
WAO Secretariat Staff Change
Stanley Mandarich, WAO’s Executive Director, will be leaving the organization this month to return to Toronto, Ontario, Canada, where he will assume the position of Executive Director of the Canadian Anesthesiologists’ Society. We wish Stan well and thank him for serving WAO so ably since 2004.
We are delighted to welcome Charu Malik, PhD, as our new Executive Director of WAO from mid-January 2007. Charu, a native of India, brings considerable experience in association management; her international knowledge will be a great asset to the organization.
WAOの秘書官を長く努めていたStanley Mandarichはカナダに帰国し代わってCharu Malik博士が着任した。
WAO Long-Term Research Fellowship
Congratulations to Dr. Andrea Vereda-Ortiz, who has been awarded the first WAO Long-Term Research Fellowship, to commence in 2007. Dr. Vereda will undertake a fellowship with Dr. Hugh Sampson at Mount Sinai Hospital, New York, to study "Comparative characterization of legume reactivity between patients of Spain and the United States." WAO received a number of excellent applications, and we thank all those who applied for their interest in this program.
WAO Short-Term research fellowship
Dr. Eleonara Dehlink has completed her WAO Short-Term Research Fellowship at the laboratory of Dr. Edda Fiebiger, Boston’s Children’s Hospital. The fellowship funding was used to help Dr. Dehlink learn new techniques for her research 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-intestinal tract? an in vitro approach". To read a report on Dr. Dehlink’s work, click here.
WAO Educational Needs Survey
The World Allergy Organization’s educational programs are designed to assist Member Societies by providing educational materials that bring together the expertise and experience of allergists worldwide. We are currently surveying our members, and would value the comments of the readers of WAO News and Notes about their own educational needs and preferences. Please click here to complete the short, on-line survey.
Future World Allergy Congresses
For all future WAO Congresses, the WAO Congress Council has recently recommended that WAO solicit proposals from specific world regions on a rotational basis. This will ensure a fair, worldwide representation over the years. The WAO Board of Directors met recently and determined that Europe would be the preferred site of our 2013 Congress. The final decision on a location within Europe will be made at the WAO House of Delegates meeting during the 2007 WAC in Bangkok.
2-6 December 2007 - Bangkok, Thailand (http://www.congrex.com/wac2007/ )
2009 - Buenos Aires, Argentina
2011 - Cancun, Mexico
World Allergy Forum Held at the 2007 ACAAI Annual Scientific Meeting:
World Allergy Congress 2007 Symposium
"Global Issues in Allergy: Answers for a Worldwide Problem"
Our international faculty was chaired by Michael A. Kaliner and provided a worldwide update on allergic emergencies. The first speaker, Bob Q. Lanier (Fort Worth, TX, USA), presented an update on acute and severe asthma, and the presentation by Ruby Pawankar (Tokyo, Japan) focused on anaphylaxis. The symposium was concluded by Michael A. Kaliner (Wheaton, MD, USA), who discussed angioedema.
Click here to view abstracts and presentation slides.
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
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And In Other News
Allergy Book Reviews
Ultrastructure of Mast Cells and Basophils
Ann M Dvorak
List price: $135.50 USD
Available from: Karger
Institute of Clinical Pathology and Medical Research and Westmead Millennium Institute, Westmead, NSW, Australia
This monograph reviews the work undertaken in the laboratories of the author and her collaborators between 1991 and 2001. It follows upon an earlier (1991) monograph and begins by reinforcing the ultrastructural definitions that allow differentiation of the (closely related) mast cell and basophil, in mouse, guinea pig and human.
The well ordered text explores the ultrastructural localization of cytokines, proteases, histamine, Charcot-Leyden crystal protein and other factors in the organelles of mast cells and basophils. The scope of this text then broadens to include the role of vesiculo-vacuolar organelles and their role in the trans endothelial secretory pathway.
While this book will prove to be of broad based interest to medical professionals, its most significant value should be to those researching the basic science of immunology and allergy and the interaction of mast cells in tissue based systems.
There is a balanced blend of both well established electron microscopy methodology (including immuno-gold labeling), together with enzyme affinity gold techniques and ultrastructural in situ hybridization. Techniques are adequately described and effectively referenced. The 185 illustrations are of consistently good quality.
For these specialized individuals, the book will find its way into personal libraries. This text should also reside on the shelves of the libraries of those institutions where basic ultrastructural cell research is undertaken.
Asthma in the Workplace, 3rd Edition
David I. Bernstein, et al.
List price: $249.95
Available from: CRC Press
University of South Florida College of Medicine, Tampa, FL, USA
This is the third edition of a reference text that reviews the key components of work‑related asthma. The book is organized into four main sections, including: General Considerations, Assessment and Management, Specific Agents Causing Occupational Asthma with a Latency Period, and Specific Disease Entities and Variants.
The purpose is to provide the clinician with a detailed reference covering all relevant aspects of occupational asthma, especially those relating to disease mechanisms, causative agents, clinical diagnosis and treatment.
Discussion is targeted to clinicians and clinical researchers who have an interest in occupational lung disease. Specialists most likely to utilize this resource include pulmonologists, allergists, clinical immunologists, and any physician with an interest in work‑related illnesses. Fellows in training will find this book to be an excellent reference text for the evaluation of occupational airway complaints.
Each chapter is logically organized, well‑written and concludes with an extensive bibliography. Over 100 tables and figures are clearly presented serving to illustrate relevant points. An excellent appendix is included that lists known causative agents in occupational asthma along with key references. A complete index concludes the text.
This book provides a comprehensive review of clinically relevant topics in occupational asthma written by nationally and internationally recognized experts in the field. This text is an outstanding reference resource for the clinician, clinical scientist or clinical fellow with an interest in work‑related asthma.
Find more allergy book reviews on the WAO Website here.