WAO News and Notes - Medical Reviews
Volume 5, Issue 3
March 2008

wao journalIntroducing a new resource, the World Allergy Organization Journal (WAO Journal), the official publication of the World Allergy Organization (WAO). Packed full of original research, in-depth reviews and up-to-the-minute reports, this online-only journal offers the ideal forum for allergy/immunology professionals worldwide to share knowledge and explore groundbreaking topics.

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Medical Journal Reviews
Prof. Richard F. Lockey, MD, WAO Web Editor-in-Chief, reviewed premier medical journal articles for practicing allergists.

1. Oral or IV prednisolone (P) in the treatment of COPD exacerbations - A randomized, controlled, D-B study.
435 patients were referred for a COPD exacerbation warranting hospitalization. 107 received P, 60 mg IV and 130, 60 mg orally. Rx failure, the primary outcome, was defined as death, admission to ICU, readmission to ICU because of COPD, or intensification of pharmacologic Rx during a 90-day follow-up period. Overall Rx failure within 90 days was similar in both groups. The authors conclude that oral P is equally effective as is IV Rx for up to 90 days after starting Rx. Editor's comment: Oral vs. IV P Rx for COPD is easier and probably more cost effective; findings are similar for Rx of asthma exacerbations. de Jong YP, et al., Chest 2007; 132(6):1741-47. (editorial: Tashkin, pp. 1728-29).


2. Budesonide/formoterol (B/F) maintenance and reliever Rx: impact on airway inflammation in asthma.
After two weeks of usual therapy, 1538 patients were randomized for six months to open-label B/F maintenance and reliever Rx 160/4.5g 2X/day and as needed or guideline-based conventional best practice. Severe asthma exacerbations, reliever medication use and total inhaled glucocorticosteroid (IC) dose were analyzed in all patients. No differences were seen in time to severe exacerbation and severe asthma exacerbation rate. However, there were numerically fewer ED visits/hospitalizations with B/F maintenance and reliever Rx (4.4 vs. 7.5/100 patients/year; 41% reduction; p=0.09). Mean total IC dose, reliever use, asthma medication costs and total annual costs per patient were all significantly lower with B/F maintenance and reliever Rx (all p<0.01). The authors conclude that B/F maintenance and reliever Rx is superior compared to conventional best practice in patients with persistent asthma. Side-effects were similar in the 2 groups. Editor's comment: B/F 160/4.5g 1 spray 2X/daily plus additional doses as needed up to 12 inhalations daily is effective asthma therapy. Sears MR, et al., ERJ Express 2008; doi: 10.1183/09031936.00104007.


3. Clarithromycin (CL) targets neutrophilic (N) airway inflammation in refractory asthma.
45 patients with severe refractory asthma were randomized to receive CL 500 mg 2X/daily or placebo for eight weeks. The primary outcome was sputum IL-8 concentration. Other inflammatory outcomes included sputum N numbers and concentrations of N elastase and matrix metalloproteinase (MMP)-9. Clinical outcomes included lung function, airway hyperresponsiveness to hypertonic saline, asthma control, QOL and symptoms. CL significantly reduced airway concentrations of IL-8, N numbers, and improved QOL scores vs. placebo. Non-significant reductions in N elastase and MMP-9 concentrations were also observed. The authors conclude that CL can modulate IL-8 levels and N accumulation and activation in the airways of refractory asthma and could reduce noneosinophilic, particularly N inflammation, in asthma. Editor's comment: CL could be helpful in individuals with N airway inflammation and refractory asthma. Simpson JL, et al., Am J Res Crit Care Med 2008; 177:148-55. (Abstract: http://ajrccm.atsjournals.org/cgi/content/abstract/177/2/148) atsjournals

難治性重症喘息患者に対してクラリスロマイシンを投与し、好中球炎症のマーカーであるIL-8、MMP-9, 好中球エラスターゼ、喀痰中好中球などで評価した。MMP-9, 好中球エラスターゼは有意な変化を認めなかったが、IL-8, 好中球数、QOLで改善を認めた。

4. Platelet-activating factor (PAF), PAF acetylhydrolase (PAFA), and severe anaphylaxis (A).
PAFA activity was measured in 41 patients with A and 23 controls. PAFA was also measured in nine patients who had fatal A to peanuts and compared to 26 nonallergic pediatric controls (C), 49 nonallergic adult C, 63 patients with mild peanut allergy, 24 patients with nonfatal A, 10 people who died of nonanaphylactic causes, 15 with life-threatening asthma, and 19 with non-life threatening asthma. PAF levels were significantly higher in the A (805595 pg per ml) than in C (127104 pg per ml, P<0.001 after log transformation) and were correlated with the severity of A. There was an inverse correlation between PAF and PAFA activity (P<0.001). The authors postulate that failure of PAFA to inactivate PAF may contribute to the severity of A. Editor's comment: The lack of adequate amounts of PAFA may contribute to increased severity of A. Vadas P, et al., N Engl J Med 2008; 358: 28-35. (editorial: Burks, pp. 79-81).


5. Allergology International.
The December issue of Allergology International contains 3 reviews on airway remodeling and asthma. The first, by Yamauchi K, et al., is entitled "Airway Remodeling in Asthma and Irreversible Airflow Limitation - ECM Deposition in Airway and Possible Therapy for Remodeling"; the second, by Tagaya E, et al., is entitled "Mechanisms of Airway Remodeling in Asthma"; and the third, by Sumi Y, et al., is entitled "Airway Remodeling in Asthma". Editor's comment: This is a nice update on the subject of airway remodeling and asthma. Yamauchi K, et al., Allergology International 2007; 56: 321-29. Tagaya E, et al., 331-40. Sumi Y, et al., 341-48.

Allergology Internationalの紹介である。山内編集委員らによる気道リモデリングの特集について nice update on the subject of airway remodeling and asthmaと紹介している。

6. Atopic features of cough variant asthma (CVA) and classic asthma (CA) with wheezing.
These authors examine specific IgE levels to seven common aeroallergens in 74 CVA patients (subjects who had a cough in absence of wheezing or dyspnea, the presence of airway hyperresponsiveness to methacholine, and a symptomatic response of coughing to bronchodilators) vs 115 CA patients of varying severity. Patients with CA had higher total IgE levels (P<0.0001), more sensitization to allergens (P = 0.03), and higher rates of sensitization to dog dander (24% vs 3%, P<0.0001), HDM (46% vs. 28%, P = 0.02), and moulds (17% vs. 7%, P = 0.047) vs. CVA. Wheezing developed in 6 (15%) patients with CVA, who were sensitized to a larger number of allergens (P = 0.02) and had higher rates of sensitization to HDM (P = 0.01) and dog dander (P = 0.02) than the 34 patients in whom wheezing did not develop. The authors conclude that atopy is related to the development of wheezing in CVA and that to prevent progression from CVA to CA, avoidance of relevant allergens may be helpful. Editor's comment: This is a nice study on CVA, a disease which is rarely studied and with which all physicians who care for patients with CA are familiar. Takemura M, et al., Clin Exp Allergy 2007; 37:1833-39.


7a. British Society for Allergy and Clinical Immunology (BSACI) guidelines for the management of allergic and non-allergic rhinitis
7b. BSACI guidelines for the management of rhinosinusitis and nasal polyposis
These two clinical guideline articles are on the subject of allergic and non-allergic rhinitis and rhinosinusitis and nasal polyposis. They summarize the medical science behind these diseases and how they should be treated. Editor's comment: Nice articles and must reading for all those interested in these subjects. Scadding GK, et al., Clin Exp Allergy 2008; 38:19-42. Scadding GK, et al., Clin Exp Allergy 2008; 38:260-75.


8. HLA-B*5701 screening for hypersensitivity to Abacavir (A)
The presence of the HLA-B*5701 allele is associated with hypersensitivity reactions to A. 1956 patients infected with HIV type 1 who had not previously received A were studied in this D-B prospective randomized study to establish the effectiveness of prospective HLA-B*5701 screening to prevent hypersensitivity reactions to A. Screening eliminated immunologically confirmed hypersensitivity reactions (0% in the prospective-screening group vs. 2.7% in the control group, P<0.001), with a negative predictive value of 100% and a positive predictive value of 47.9%. The authors conclude that HLA-B*5701 screening can prevent a specific toxic effect of A. An editorial entitled "Pharmacogenomic Biomarkers for Prediction of Severe Adverse Drug Reactions" accompanies this article. There are now at least seven biomarkers which predict reactions to: 6-mercaptopurines, irinotecan, warfarin, tricyclic anti-depressants, abacavir, carbamazepine, and ximilagatran. Editor's comment: Some pharmacogenomic biomarkers can predict severe adverse drug reactions. Mallal S, et al., N Engl J Med 2008; 358:568-79. (editorial: Ingelman-Sundberg, pp. 637-38).


9. Seafood allergy (SA) and radiocontrast media (RCM): Are physicians propagating a myth?
This is an anonymous survey of 231 faculty radiologists and interventional cardiologists at six Midwest academic medical centers to question whether SA is related to RCM reactions. 69% of the responders indicated that they inquire about a history of SA before RCM administration and 37.2% replied that they withhold it or recommend premedication on the basis of this history. The authors conclude that the myth that SA is a risk factor for RCM reactions is common among physicians. Editor's comment: SA is not a risk factor for RCM reactions. Beaty AD, et al., Am J Med 2008; 121:158.e1-158.e4.


10. Proceedings of the American Thoracic Society
This entire journal is devoted to adult and pediatric sleep-disordered breathing. It covers the epidemiology, pathophysiology, diagnosis, medical and surgical treatment, as well as potential sequelae from this disease. Editor's comment: A wonderful symposium on a very common problem in patients seen by allergists/immunologists. Mokhlesi B, Gozal D (guest eds). Proc of the Am Thoracic Society 2008; 5:135-284.


11. Supplement to the Journal of Allergy and Clinical Immunology entitled "Mini-Primer on Allergic & Immunologic Diseases."
This issue contains CME review articles on "Lymphocytes," "Dendritic Cells as Regulators of Immunity and Tolerance," "Adhesion Molecules and Receptors," "Gastrointestinal Mucosal Immunity," "Genetics of Allergic Disease," "Secondary Immunodeficiencies, Including HIV Infection," "Immunologic Lung Disease," " Hereditary Angioedema," "Anaphylaxis," and "Occupational Asthma." Editor's comment: Drs. Ed Shearer and Don Leung (eds) and the authors are to be congratulated for this wonderful JACI CME issue. JACI (Suppl) 2008; 121: S363-S411.


12. Effect of glucosamine sulfate (GS) on hip osteoarthritis (O).
This is a 222 patient randomized, controlled trial study of hip O to determine whether or not GS affects symptoms and structural progression of hip O during 2 years of Rx. Primary outcomes include pain and function subscales over 24 months and joint space narrowing after 24 months. Secondary outcomes include pain, function, and stiffness after 3, 12 and 24 months. There are no statistical differences between the Rx vs. the placebo groups. Editor's comment: GS is not effective treatment for hip O. Rozendaal RM, et al., Annals of Int Med 2008; 148:268-77.


13. Snoring (S) in preschool children: prevalence, severity and risk factors.
6,811 children aged 1-4 yrs were evaluated for the prevalence, severity and risk factors for S, especially habitual S. In 59.7% of the children, parents reported S in the previous 12 months, including 7.9% with habitual S and 0.9% with habitual S and sleep disturbance. Prevalence increased with age from 6.6% in 1-yr-olds to 13.0% in 4-yr-olds. Habitual S was associated with: one and both parents smoking (adjusted odds ratio (OR) 1.46 and 2.09, respectively); road traffic (OR 1.23); single parent (OR 1.60); and in White but not South Asian children, socioeconomic deprivation (OR 1.25 and 2.03 for middle and upper thirds of Townsend score, respectively). There was a strong association with atopic disorders, viral infections and environmental exposures suggesting a complex etiology. Editor's comment: S occurs in children and adults. Physicians should be aware that children develop sleep disorders leading to educational and behavioral problems. Kuehni CE, et al., Eur Respir J 2008; 31:326-33.


14. Systemic responses after bronchial aspirin challenge in sensitive patients with asthma.
19 patients with a history of aspirin-induced asthma underwent placebo (P)-controlled bronchial challenges with lysine-aspirin (LA). Peripheral blood was collected before and then 1 and 20 hours after challenge with P or LA and numbers of leukocyte and eosinophil progenitors determined. The challenge was positive in 13 with six having an isolated local bronchial reaction and seven systemic (bronchial and extrabronchial symptoms). Leukocyte progenitors increased significantly at 1 and 20 hours (P<0.05). Eosinophil progenitors increased significantly from mean 0.017% before challenge to 0.04% (P<0.05) at 20 hours after the challenge. At the 20 hour challenge, the increase in leukocyte and eosinophil progenitors was observed only in patients with systemic reactions. Eotaxin was also increased with positive challenges in two subjects. Bronchial challenge with LA causes a systemic reaction associated with mobilization of leukocyte and eosinophil progenitor cells from the bone marrow. Editor's comment: Aspirin sensitive asthmatics have a systemic disease, not just asthma. Makowska JS, et al., JACI 2008; 121:348-54.


Allergy Book Review

Lippincott's Illustrated Reviews: Immunology
Authors: Thao Doan, Roger Melvold, Susan Viselli, and Carl Waltenbaugh
Editors: Richard A. Harvey, Pamela C. Champe
ISBN-10: 0-7817-9543-5
ISBN-13: 978-0-7817-9543-2


Available from: Wolters Kluwer/Lippincott Williams & Wilkins
List Price: 46.95 USD

Josh Phillips, MD
Division of Allergy & Immunology, University of South Florida College of Medicine

Lippincott's Illustrated Reviews is a highly-regarded series designed to provide a review of essential topics for undergraduate, graduate, and medical students. The series is recognized for their full-color illustrations, chapter summaries, study questions, and case studies. Such learning tools synthesize clinical and scientific concepts, giving students a more complete review. This latest addition to the series lives up to their high standards.

The authors have divided the text into four units, representing larger immunological concepts: Self/Non-self, Innate Immune System, Adaptive Immune System, and Clinical Aspects of Immunity. These broad topics are subdivided into chapters, with emphasis on molecular aspects, MHC recognition, lymphocyte development and activation. Later chapters focus on specific topics such as immunodeficiency, transplantation, and laboratory techniques to evaluate immunity.

This series is well-known for its figures, and an early figure stands out in its depiction of infection as a monopoly-style board game. A roll of the dice may land a microbe on a natural killer cell (depicted as a rabid dog) or an immune defect, in which the microbe advances to the end (sepsis). Another figure depicts the neutrophil as a restaurant patron selecting from a limited menu, while the lymphocyte can mix-and-match from dozens of palatable options. This effectively illustrates the contrast of the relatively limited innate response vs. the adaptive response in which clonally-derived lymphocytes can respond to 10 10 different receptors.

At the conclusion of each chapter there are five-to-ten USMLE-style questions to solidify core concepts, accompanied by answers and explanations on the same page. This is preferred over other texts, which may refer back to a page number for the explanation, but some may be tempted to merely read the explanations rather than answer the questions. Also, the clinical applications and case presentations are short, too few in number, and not followed by questions.

The preliminary chapters oversimplify some concepts, but later chapters are quite thorough, using molecular cell biology to explain complex ideas. As such, this text may be too advanced for undergraduate study and overly broad for PhD candidates in immunology. However, medical students looking for more detail than the typical "high-yield" review may find the balance ideal. While this review is by no means all-inclusive, it provides a thorough review of important topics and concepts in immunology.

Find more allergy book reviews on the WAO Website here.

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