Insights, strategies, asthma and allergy risk factors, and the allergist/immunologist: Challenges to be met and promises to keep!

Abstract

The woods are lovely, dark, and deep, But I have promises to keep, And miles to go before I sleep, And miles to go before I sleep. —Robert Frost True to the publication of diverse issues that comprise and challenge the field of allergy and immunology and the allergist/immunologist, this issue of the Allergy and Asthma Proceedings features a spectrum of articles that we hope will provide greater insight and clinical utility for the readership in seven major areas of current research. These include the following: asthma, allergens and allergy immunotherapy, the interplay of environment on the development of allergic disease, hereditary angioedema, drug allergy and immunodeficiency, and the inner city asthma epidemic. The idea that certain features of life in poor urban areas could promote asthma dates back to more than a half century ago when researchers began to describe an “inner-city asthma epidemic” of high asthma prevalence and morbidity in disadvantaged populations living in poor areas of large cities. In more recent years, major research efforts are being directed to the study of the causes of inner city asthma that contribute to high morbidity and mortality, particularly to vulnerable children who live in these inner-city disadvantaged populations. In school children, it manifests as absences and decreased academic performance attributable to frequent asthma exacerbations. In an insightful article, Szefler 1 used a case-based format to overview the unmet needs associated with inner-city asthma and discussed the myriad of factors that contribute to asthma exacerbations in this setting, including obesity, allergic sensitization, and lack of medication adherence. His report offers novel strategies to predict and prevent seasonal exacerbations of asthma, use new medications, and initiate school-centered asthma programs designed to assure optimal adherence. Because of the great interest and importance of the myriad of environmental, medical, and socioeconomic asthma risk factors that contribute to the “inner-city asthma epidemic,” the article by Szefler 1 was chosen for this issue's “For the Patient” section. The topic holds special interest and offers an important role for the allergist/immunologist in addressing this important national problem and presented both promises to keep and challenges to be met. The challenges are before us, and, in the ensuing decades, the allergist/immunologist will have a dual responsibility: one is scientific, the other is social. First, as a clinician at the translational interface of science and clinical applicability, the allergist/immunologist must take an active role in identifying substantive asthma and allergy risk factors, and new areas for clinical application to patient management unimaginable in past years. The promise of allergy immunology is to assure that the health of our patients, and particularly of children, flourishes and is attended to by professionals with competencies and skills necessary to provide optimal patient management. The challenge for the allergist/immunologist then is to guarantee that the promise is kept. The article by Szefler 1 is a gentle reminder that the allergist/immunologist must also assume the responsibility as physician-educator and child advocate that children might prosper on this earth. Another innovative asthma treatment strategy that is addressed in this issue of the Proceedings is the use of a single inhaler (inhaled corticosteroid/long-acting β-agonist combination) for both maintenance and reliever therapy. Lin et al. 2 performed a 12-week, multicenter, open-label therapeutic phase IV study in which patients with partially controlled or uncontrolled asthma were switched from their usual asthma treatment to a budesonide/formoterol (160/4.5 μg, one inhalation twice daily and as needed) regimen. The authors found that asthma control and quality of life improved in Chinese patients who received treatment with the budesonide/formoterol maintenance and reliever therapy. Inhaled corticosteroids, although efficacious for the treatment of persistent asthma, have the potential for adverse effects, including adrenal suppression when used at high doses or in susceptible individuals. Kowalski et al. 3 performed a systematic review and quantitative analysis of 64 published studies with the goal of synthesizing all currently available studies on novel, freon-free inhaled corticosteroid preparations. From their analysis, they reported that the strongest dose-response urinary cortisol suppression was observed in patients treated with beclomethasone, followed by fluticasone and budesonide, but that no significant urinary cortisol suppression was associated with ciclesonide. Although antioxidant dietary supplements have long been proposed for the treatment of asthma, no convincing evidence has been available. Tenero et al. 4 attempted to provide efficacy data by retrospectively evaluating the effect of an antioxidant dietary supplement on exhaled nitric oxide and lung function over a 1-month period in 47 pediatric patients on stable antiasthma treatment. Based on their findings, the authors indicated that supplementation with a nutraceutical regimen of antioxidants and anti-inflammatory compounds may be associated with reduced airway inflammation. Omalizumab, the anti- IgE flagship monoclonal antibody, has established therapeutic efficacy for the treatment of patients 12 years of age and older with moderate-to-severe persistent allergic asthma who are not controlled on inhaled steroids. More recent studies demonstrated that omalizumab may also provide benefit in the management of selected patients with chronic rhinosinusitis (CRS). In this issue of the Proceedings, Clavenna et al. 5 performed a retrospective case-control study to examine the clinical efficacy of omalizumab in patients with both asthma and CRS compared with those with asthma alone. The authors reported that improved pulmonary function associated with omalizumab treatment was more likely to be observed in patients with both asthma and comorbid CRS than in those without CRS. There exists a great need and considerable potential clinical utility to identify biomarkers that would serve as predictors of favorable responses of patients with severe asthma to treatments, e.g., omalizumab. In this issue of the Proceedings, Tsybikov et al. 6 evaluated chronic rhinitis biomarkers in an attempt to better assess upper airway inflammatory phenotypes in subjects with allergic rhinitis, nonallergic rhinitis, and CRS. They propose that chronic rhinitis can be categorized into several disease phenotypes by assessment of four chronic rhinitis biomarkers: endothelin-1, thymus and activation-regulated chemokine (TARC/CCL17), and α-defensins. Transitioning from asthma to a focus on allergens and allergy immunotherapy are two articles of studies that examined the diagnostic dependence of antibody levels and allergen potency on allergic disease management. The first article, by Ciprandi et al., 7 investigated the practical role of Bet v 1 IgE in differentiating birch allergy from oral allergy syndrome. The authors indicated that a serum IgE cutoff value to Bet v 1 could be a useful marker for differentiating among different birch pollen sensitization phenotypes. The second article addressed a comparison of the potency of allergy extracts used in Europe compared with those used in the United States. Larenas-Linnemann and Mosges 8 performed further data analysis to facilitate interpretation of SLIT dosing, as recommended by European manufacturers, relative to U.S. SCIT maintenance dosing. They reported that, for more than half of the products, SLIT is not “high dose,” as has originally been recommended; however, how this potency relates to efficacy is not clear. The association of the environment and infectious disease on allergic disease expression is addressed in three articles found within this issue. Kim et al. 9 demonstrated that exposure to elevated carbon monoxide levels during infancy increases the risk of development of allergic rhinitis and of atopic dermatitis symptoms in South Korean children. Kim et al. 10 investigated the effects of ethnicity and environmental exposures on eczema in Hispanic white and non-Hispanic white children who participated in the Southern California Children's Health Study. They reported finding an ethnic difference, with Hispanic white children having a lower prevalence of eczema than non-Hispanic white children, which could not be accounted for by sociodemographic differences. The effects of parental history of allergic disease and indoor environmental exposures on eczema varied by ethnicity indicating that the etiology of eczema may differ in different ethnic groups. The role of infectious disease was next examined by Imbalzano et al., 11 who performed a systematic review about the association between urticaria and viral infections. They presented their data analysis, which indicated viral infection as a potential trigger and sometimes as the main etiologic agent in causing acute or chronic urticaria. Unlike chronic urticaria, hereditary angioedema is a rare and potentially life-threatening disease characterized by recurrent angioedema, which has been a frequently visited theme in recent issues of the Proceedings. 12–27 Abdominal symptoms of hereditary angioedema typically mimic numerous abdominal emergencies and may delay the correct diagnosis and inappropriate treatments. Ucar et al. 28 report on the difficulties experienced by patients with hereditary angioedema in Turkish emergency departments, which is representative of the unmet needs reported globally. Drug allergy, in particular, nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity has been a recurrent theme in the Proceedings. 29–33 Within this issue, Topal et al. 34 sought to determine the diagnostic value of the clinical history and also to determine safe alternative medications in 64 children who were evaluated for immediate-type reactions to NSAIDs. They reported that two historical features, the emergence of symptoms within an hour of taking the drug and the presence of hypersensitivity to multiple NSAIDs increased the possibility of true NSAID hypersensitivity. In addition, they identified three safe alternative drugs in patients with multiple NSAID hypersensitivity: nimesulide, low-dose acetaminophen, and tolmetin sodium. This issue's Patient-Oriented Problem Solving “POPS” case presentation shifts our focus to immunodeficiency. The POPS case presentation is a recurring feature of the Proceedings, which, as per tradition, is written by an allergy/immunology fellow-in-training from one of the U.S. allergy/immunology training programs. The purpose of the POPS series is to provide an innovative and practical learning experience for the novice allergist/immunologist in-training by using a didactic format of clinical presentation and deductive reasoning. In this issue's POPS, Buyantseva et al.,35 from the Penn State Hershey Medical Center, lead the reader through this process by describing the evaluation of a 73-year-old woman who presented with chronic watery diarrhea, weight loss, and frequent sinus and nail fungal infections. This case report illustrated the complexity of the differential diagnostic process for this clinical presentation and the importance of a detailed history, physical examination, and appropriate laboratory assessment in arriving at a correct diagnosis. In summary, the collection of articles found within the pages of this issue provides further insight into important allergic, cutaneous, and respiratory disorders that afflict patients whom the allergist/immunologist serve. In keeping with the overall mission of the Proceedings, which is to distribute timely information regarding advancements in the knowledge and practice of allergy, asthma, and immunology to clinicians entrusted with the care of patients, it is our hope that the articles found within this issue will help foster enhanced patient management through efficient workup and optimal therapy for a great diversity of clinical problems. On behalf of the editorial board, we hope you enjoy the diversity of literature offered in this issue of the Proceedings.