Lanny J. Rosenwasser

Regulatory T cells control the development of allergic disease and asthma.

The role of T(H)2 cells in the pathogenesis of allergy and asthma has been well described. However, the immunologic mechanisms that downmodulate and protect against the development of these disorders are poorly characterized. A spectrum of CD4+ T cells, including T(H)1 cells, T(H)3 cells, regulatory T cells, CD25+ T cells, and natural killer T cells might play a critical role in regulating these diseases and are discussed in this review.

Allergy Practice Worldwide: A Report by the World Allergy Organization Specialty and Training Council

In 2004 the World Allergy Organization’s Specialty and Training Council conducted a survey of World Allergy Organization (WAO) member societies to obtain information about the status of the specialty of allergy worldwide. Responses were received from 33 countries, representing a population of 1.39 billion people, of whom it was estimated that 22% may suffer from some form of allergic disease. Allergy was reported by 23 respondents to be a certified or accredited specialty in their country, and the number of certified allergists per head of population ranged from 1:25 million to 1:16,000. Allergists were ranked as the fifth most likely clinicians to see cases of allergic asthma, third most likely to see allergic rhinitis, and fourth most likely to see eczema or sinusitis. Nine countries only reported that children with allergic diseases would be seen by a pediatrician with appropriate training. The survey results highlight a pressing need for the development of allergy services worldwide.

Association of Transforming Growth Factor-β1 Single Nucleotide Polymorphism C-509T with Allergy and Immunological Activities

Background: A single nucleotide polymorphism (SNP) C-509T within the tumor growth factor β1 (TGFβ1) gene has been associated with atopic asthma and asthma severity. To further understand the mechanisms involved, the association of C-509T with allergy, T-lymphocyte proliferation and plasma TGFβ1 concentration has been explored in a case-control study with allergic and non-allergic subjects. Methods: The recruited subjects including allergic (n = 38) and nonallergic (n = 25) participants have been genotyped for C-509T using allele discrimination assay. Association of C-509T with allergy status was examined using logistic regression analysis in both dominant and recessive models. Association of C-509T with T-cell proliferation in control and antigen-stimulated peripheral blood mononuclear cells (PBMCs), plasma TGFβ1 and total IgE level were tested by multiple regression analysis. Results: Individuals with homozygous mutant TT genotype showed a higher risk of allergy (TT: odds ratio = 5.099, 95% confidence limit: 1.355–19.190, p = 0.016) after covariates were adjusted. A trend to increased plasma TGFβ1 in subjects with T allele has been discovered. In the meantime, the T allele is associated with lower T cell proliferation in controls and maximum response to above antigens. A low T-cell proliferation is correlated with higher plasma TGFβ1 concentration (p < 0.01). The in vitro studies confirmed the suppressing effect of TGFβ1 on T-cell proliferation at physiological range. A significant inhibitory effect on IL-4 production was also observed. Conclusions: A C to T base change in TGFβ1 SNP C-509T has been associated with a higher risk of allergy. The mechanisms are not clear. Elevated TGFβ1 levels associated with the C-509T polymorphism might suppress immune activation as well as Th2 cytokine production.

Characterization of aerosol output from various nebulizer/compressor combinations

OBJECTIVESnDifferent commercially available nebulizers and compressors are available. However, the optimal combination for drug delivery is unknown.nnnMETHODSnFlow rates of five different compressors (n = 3/compressor) tested alone and in combination with five different commercial nebulizers (n = 9 of each brand of nebulizer) were evaluated. Thereafter, the performances of the different nebulizers were evaluated using 2.5 mg albuterol solution (0.5 mL) added to 2.5 mL saline at flow rates of 2, 3, 4, and 5 L/minute using a laser particle analyzer. Volume median diameter and percentage of particles in the respirable range (1-5 microm) were calculated from this data. Time for nebulization (in seconds) and residual volume (in milliliters) were also recorded.nnnRESULTSnThe mean flow rates for the compressors evaluated without a nebulizer attached ranged from 6.6 L/minute (LifeCare Freedom-neb; LifeCare International, Lafayette, CO) to 12.2 L/minute (DeVilbiss Pulmo-Aide; DeVilbiss Health Care, Somerset, PA). Flow rates for the nebulizer/compressor combinations ranged from 2.08 L/minute (Pari LC Jet Proneb; Pari Respiratory Equipment, Richmond, VA) to 5.42 L/minute (Puritan Bennett Raindrop; Puritan Bennett, Lenexa, KS/Omron Compare; Omron, Health Care,Vernon Hills, IL). Using the repeated measure ANOVA model, the interaction between flow rate and device was significant (P < 0.001) for both percentage of particles in the respirable range and log volume median diameter. It was observed that the percentage of particles in the respirable range for the Pari LC Jet did not increase across flow rates in contrast to the other 4 nebulizers. All comparisons to the Pari LC Jet at 2 L/minute were significant.nnnCONCLUSIONSnMarked variability exists in the flow rates among different commercially available compressors used for home nebulization of inhaled pulmonary medications. Different nebulizer/compressor combinations have markedly different performance characteristics which could result in different efficacy and safety profiles of the medications being administered via these devices. We recommend that this type of information be used as a starting point for selecting different nebulizer/compressor combinations. Further clinical evaluation is warranted.

Systemic allergy to endogenous insulin during therapy with recombinant DNA(rDNA) insulin

BACKGROUNDnClinically significant allergic reactions with insulin therapy are known to occur. There have been rare reports of allergic reactions to endogenously secreted insulin manifested as insulin resistance. No reports of systemic or local allergic reactions to endogenous insulin have previously been cited, and no immunologic reactions to endogenous insulin have been reported during therapy with recombinant (rDNA) insulin.nnnMETHODSnWe report a case in which the patient, a 28-year-old black woman who initially presented with gestational onset diabetes but postpartum continued to require insulin, developed generalized allergic reactions during therapy with subcutaneously injected rDNA insulin. Similar reactions occurred with sulfonylurea therapy. She was unable to tolerate any pharmacologic therapy for diabetes without concurrent use of at least 10 mg of prednisone per day.nnnRESULTSnSkin testing with the insulin preparations were positive, while skin testing to the sulfonylurea hypoglycemic agents were negative. IgE antibodies to insulin where present in high titer. Oral challenge to sulfonylurea hypoglycemic agents produced generalized urticarial reactions coinciding with time of peak insulin secretion. Oral challenge to other medications containing sulfa produced no adverse reaction. Biphasic hypersensitivity reactions occurred during attempts at desensitization which were futile without simultaneous glucocorticoid therapy.nnnCONCLUSIONSnThis is the first report of local and systemic allergic reactions to endogenously secreted insulin in association with rDNA insulin therapy. Although immunologic complications with rDNA therapy appear less frequently than with insulin preparations, this case illustrates the need for continued awareness for potential allergic complications occurring with rDNA insulin therapy.

Requirements for physician competencies in allergy: key clinical competencies appropriate for the care of patients with allergic or immunologic diseases: a position statement of the world allergy organization.

Allergic diseases are quite prevalent worldwide, and the incidence of allergy is increasing everywhere [1-7]. Because allergic and immunologic processes overlap all organ systems, allergy is not always taught in medical schools as a separate subject. Indeed, lack of recognition of the specialty and of the need to teach about allergic and immunologic diseases results in allergy not being included at all in some medical school curricula [8]. With an estimated 22% of the global population experiencing allergic and immunologic diseases, it is time to recognize and strengthen education in allergy and immunology [8]. n nThe World Allergy Organization (WAO), an alliance of 74 national and regional allergy societies, created this consensus document to establish educational guidelines for worldwide application to help identify and correct allergy education and training deficiencies and to define appropriate competencies. In creating this consensus, it is recognized that each country has its own principles and goals in medical education at the undergraduate and postgraduate levels. This document defines what WAO considers medical practitioners should know to care appropriately for allergic patients.

What is an Allergist? Reconciled Document Incorporating Member Society Comments, September 3, 2007

An allergist is a physician who has successfully completed both a specialized training period in allergy and immunology and a training period in either internal medicine, or a sub-specialty of internal medicine such as dermatology, pneumology, or otorhinolaryngology, and/or pediatrics. Subject to national training requirements, allergists are also partially or fully trained as clinical immunologists, because of the immune basis of the diseases that they diagnose and treat. In most countries, the approved period of specialty training in allergy and immunology will be two to three years of specific, intense training. Depending on national accreditation systems, completion of this training will be recognized by a Certificate of Specialized Training in Allergy, in Allergy and Immunology, or in Allergy and Clinical Immunology, awarded by a governing board. In some countries this will follow successful completion of a certification test, and in other countries by competencies being signed-off by a training supervisor. n nFully trained allergists make an important contribution to designing local care systems and delivering the necessary care for patients with allergic diseases. Allergists act as advocates for patients, and support and argue the case for better education of the primary and secondary care physicians and other health care professionals who also care for allergic patients. Allergists should be available to provide care for the more complicated problems that are beyond the purview of well-trained primary and secondary care physicians and other health care professionals. The main defining characteristics of an allergist are the appreciation of the importance of external triggers in causing disease, and the knowledge of how to identify and manage these diseases, together with ex-pertise in appropriate drug and immunological therapies. This approach to diagnosis and therapy is a core value of the allergy specialist, and contrasts the allergist with many of the organ-based specialists whose patient bases may overlap with the specialty. n nThe unique training requirements for an allergist are detailed in Requirements for Physician Training in Allergy: Key Clinical Competencies Appropriate for the Care of Patients with Allergic or Immunologic Diseases: A Provisional Position Statement of the World Allergy Organization.[1] In that document, the levels of allergy training required of first-, second-, and third-level physicians are documented, differentiating the training and knowledge base of an allergy specialist from that of primary care physicians and organbased specialists. The American Academy of Allergy, Asthma and Immunology has also published guidelines: Consultation and Referral Guidelines Citing the Evidence: How the Allergist/Immunologist Can Help.[2] The European Union of Medical Specialists Allergy Training Syllabus [3,4] is available online at the World Allergy Organization Web site:http://www.worldallergy.org/allergy_certification/index.shtml.

Critical Documents on Cow's Milk Allergy and Anaphylaxis: Two Recent WAO Position Papers.

The purpose of this editorial is to highlight the recent ratification as WAO Position Papers of 2 important documents published in the World Allergy Organization Journal (WAO Journal). n nThe World Allergy Organization (WAO) Guidelines on the Diagnosis and Rationale against Cows Milk Allergy (DRACMA) Guidelines, ratified as a WAO Position Paper by the WAO House of Delegates, March 21, 2011, involves a significant pediatric food allergy problem and provides invaluable guidelines for the clinician. This impressive collection of information on this worldwide problem will help in the management of cows milk allergy, which has profound implications for growth and development and the health of children worldwide. Under the able leadership of Professor Alessandro Fiocchi (Italy), the Chair of the WAO Special Committee on Food Allergy, an international group has put together a scholarly and well-appointed review of all the issues related to cows milk allergy (CMA), ranging from methodology and epidemiology through a variety of other aspects of the clinical syndrome. DRACMA provides the guidelines for diagnosing CMA, and the proper natural history treatment alternatives ranging from avoidance through identification of milk derived from a variety of other sources, including unusual sources, which can be used for dietary supplementation. DRACMA employed evidence-based methodology utilizing the criteria of Grading of Recommendations Assessment, Development and Evaluation (GRADE) in its analysis of the literature. n nWorld Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis, the WAO Position Paper ratified on February 18, 2011, is a thorough, extensive work completed by worldwide anaphylaxis and allergy experts of the WAO Special Committee on Anaphylaxis led by Chair, Professor F. Estelle Simons. In addition to clearly defining, in a concise manner, the syndrome, its severity, and the possibility for treatment, the document has also provided a very clear and detailed management plan for acute anaphylaxis in both high- and low-resource areas. This is an important stride forward and the WAO Journal as always looks to better care for allergy sufferers at risk for anaphylaxis and for significant morbidity and mortality. This position paper is an excellent resource to help those circumstances. n nThe Position Paper series within the WAO Journal is intended to address the needs of the profession worldwide. Along with the 2 most recent documents, and another on the state of sublingual immunotherapy (SLIT), the series also includes a treatise on defining an allergist, basic qualities of an allergist, training required for allergists, and educational requirements--all to impart allergy education to students, residents, and practitioners. The WAO and the WAO Journal will continue to invest in the development and identification of guidelines for treating important, clinically relevant syndromes associated with allergic disease such as cows milk allergy or anaphylaxis. n nThe recently ratified position papers and other WAO documents published in WAO Journal can be accessed in the following linked list of titles: n n• World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cows Milk Allergy (DRACMA) Guidelines n n• World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis n n• Sub-Lingual Immunotherapy: World Allergy Organization Position Paper 2009 n n• Recommendations for Competency in Allergy Training for Undergraduates Qualifying as Medical Practitioners: A Position Paper of the World Allergy Organization n n• Requirements for Physician Competencies in Allergy: Key Clinical Competencies Appropriate for the Care of Patients With Allergic or Immunologic Diseases: A Position Statement of the World Allergy Organization n n• What Is an Allergist?: Reconciled Document Incorporating Member Society Comments, September 3, 2007

A 49-year-old male with intractable dyspnea, wheeze, and cough

HISTORY OF PRESENT ILLNESS A 49-year-old nonsmoking male initially presented to our institution 3 years ago with a history of steroid-dependent asthma since age 14. Before this evaluation he had been on glucocorticoid (GC) doses as high as 120 mg prednisone daily and had rarely been weaned completely from oral GCs. Chronic symptoms included dyspnea on exertion, episodic wheeze that symptomatically responded to bronchodilator, and cough that was productive of clear sputum. There was no history of chest pain or hemoptysis. Viral upper respiratory tract infections frequently led to exacerbations requiring a transient increase in his oral GC dose. He had noted that the duration of these increases was becoming longer over time. Repeated chest imaging in the past did not show evidence of infiltrates or other significant abnormalities. Confounding factors related to his asthma included allergic rhinitis, gastroesophageal reflux disease, and aspirin intolerance. His aspirin allergy resulted in flares of his asthma and rhinitis symptoms, but he had been successful in avoiding all overthe-counter preparations containing aspirin before and during our evaluation. His medication regimen for his asthma included oral GC, a high-dose inhaled steroid, a long-acting -agonist, and a rescue inhaler. Skin testing demonstrated sensitivity to trees, grasses, weeds, and cats. He was treated aggressively for his rhinitis complaints with nasal steroids as well as new generation antihistamines. His reflux disease was also treated with twice-daily proton pump inhibitor. With this therapy his rhinitis as well as reflux symptoms improved, but he did not experience relief with regard to his wheeze and dyspnea on exertion. Given his aspirin allergy it was decided that he should undergo aspirin desensitization. We felt that his asthma symptoms may improve if his upper respiratory symptoms responded favorably to this procedure. He completed the desensitization procedure without difficulty and was maintained on 650 mg twice a day. His medication regimen was also augmented at that time to include a leukotriene receptor antagonist as well as a 5-lipoxygenase inhibitor. Six months after this, he again reported that his lower respiratory symptoms were progressive. His dose of oral prednisone at that point was 20 mg daily. His past medical history was remarkable for eczema that resolved as a child and osteopenia associated with chronic oral steroid use. There was no history of trauma to the chest. He was a lifelong nonsmoker and had no occupational exposures or occupation-related triggers for his symptoms. He has been employed as a software engineer for the past 25 years. Hobbies were confined to watching movies and walking. Family history was positive for atopy and asthma. The patient lived in a new home, which was carpeted. The house had forced air heating and a humidifier. He also had 3 dogs as pets, but they remained outdoors. Review of systems was remarkable for weight gain associated with his steroid use and profound snoring according to his wife.

New Initiatives at the WAO Journal.

Since the January 2009 posting, there have been changes at the World Allergy Organization Journal that are worth noting. Prof. Johannes Ring, who led the Journal as Editor-in-Chief in the first critical year of the WAO Journal, has moved to the position of Executive Editor. In this position, he will oversee issues related to Editorials that are published in the WAO Journal. As Editor-in-Chief, Prof. Ring skillfully handled the transition from the prior Allergy and Clinical Immunology International Journal to the new online-only WAO Journal. Prof. Rings effort placed the Journal on the right track to achieve an advantageous position in the pursuit of goals that have been set out for it by the World Allergy Organization (WAO). n nEditor-in-Chief responsibilities now reside with Dr. Lanny J. Rosenwasser. In addition to the possibility of easier and immediate worldwide access, the other major benefit of an online journal is the accelerated production process, allowing monthly postings of accepted manuscripts. I am working with the editorial team not only to further streamline the review process for submitted manuscripts but also to continue to reduce production time so that quality manuscripts are made available to readers as quickly as possible. n nThe overall quality of WAO Journal has been excellent and there are a number of new initiatives I have planned for this year to maintain and extend this excellence. To supplement the flow of unsolicited submissions, we will be publishing reviews and papers under three separate content banners. We intend to publish a review series entitled Clinical Reviews in Allergy and Immunology with specific clinical relevance and practical measures that are critical for the practice of allergy anywhere in the world. The papers within this series will examine issues of drug and aspirin sensitivity, drug desensitization, natural history of allergic diseases, asthma, atopic dermatitis, and environmental and socio-economic concerns that impact the practice and delivery of care for allergic diseases and that have so far not received the attention they deserve. This series will also provide a vehicle to highlight newer approaches for the evaluation of disease and outcomes concerning treatments and interventions, and keep abreast with evolving developments in informatics, telemedicine, and web-based learning. Focusing on the practical and the new, this series will aim to become indispensable to the clinical practitioner. n nA second series of papers will be on Basic and Clinical Translational Science in Allergy and Immunology. These papers will address pathogenic mechanisms in allergic diseases and examine new, cutting-edge information that extends our understanding of pathogenesis and disease function. Technical advances (including evaluation of systems biology, nanotechnology, and other new approaches to the science of allergy and immunology) and the application of new paradigms and technologies influencing our understanding of the pathogenesis of allergic disease will also be detailed within this series. In keeping with its aim of capturing and discussing the latest advances, this series will have papers on the new roles of cytokines, innate immune system reactions, tissue remodeling, immunopharmacology, pharmacogenomics, and so forth. n nComplementing the practical and the latest will be a more personal series, Notes of Allergy Watchers, published within the editorial portion of the Journal. This series will invite individuals from our field to share their varied experiences and insights by submitting viewpoints and recollections concerning the science and practice of allergy and immunology. These submissions will be encouraged to include individual personal recollections and interpretation of important issues. The Notes of Allergy Watchers will provide not only a look backward but also observations and speculations concerning the science of our discipline and projections for potential changes within our field in the future. n nNot every posting will have a selection from each of these three banners, but it is hoped that these will be ongoing series of great interest for the practice and science of allergy and immunology and WAO members all over the world. The worldwide platform of the WAO Journal offers a great opportunity for exchange of information and ideas among different regions of the world. But it is worth remembering that we are all dedicated to the care of patients with allergic diseases, and the WAO Journal is dedicated to promoting any activity that enhances our capabilities in this area and extends new knowledge and information.