Allergy and immunology: At the crossroad of inflammation and disease

The collection of articles found within the pages of this issue provides insight into the intersecting crossroads of inflammation and disease that manifest as allergic, immunologic, and respiratory disorders that afflict patients whom the allergist/immunologist serves. A classic example of this intersection is provided by Bahna,¹ in his review of the association of modernization with the increased likelihood for the development of allergic diseases and asthma. He concludes that the marked reduction in infectious diseases in recent decades has permitted the immune system to switch from fighting infectious disease agents to reacting adversely (hypersensitivity) to benign environmental agents (allergens) and even to self-antigens (autoimmunity). In a related study with regard to immune response in children who are atopic, Stamataki et al.² report that children who are atopic are more susceptible to viral respiratory infection than nonatopic controls. The authors suggest that these clinical findings support the idea of altered maturation of innate immunity in subjects who are atopic.

Transitioning to the topic of respiratory disorders (asthma and/or aspirin-exacerbated respiratory disease) are three articles, the first of which is an up-to-date summary of asthma management during pregnancy by Bravo-Solarte et al.³ This is followed by the report of Zhao et al.,⁴ who present an insightful case series of 44 patients with eosinophilic granulomatosis with polyangiitis in a matched case-control study designed to compare patients with eosinophilic granulomatosis with polyangiitis with patients with allergic asthma. In completing this trilogy of allergic, immunologic, and respiratory disorders, Tripathi et al.⁵ expand our knowledge of the long-term benefits of aspirin therapy after desensitization in patients with aspirin-exacerbated respiratory disease. Measuring the benefits of this procedure after 6 months of aspirin therapy by the 22-item Sino-Nasal Outcome Test scoring system, they demonstrate this time point to be a highly significant predictive value for long-term quality-of-life outcomes. Based on this insight, the authors suggest that low 6-month 22-item Sino-Nasal Outcome Test scores could serve as a basis for consideration of alternative therapies.

Transitioning to the topic of anaphylaxis are four articles, starting with Duffey et al.,⁶ who conducted a cross-sectional survey study of allergy/immunology and emergency medicine providers in the University of Colorado affiliated hospitals and Colorado Asthma and Allergy Society, comparing the variation in management approaches for allergic reactions between the specialties. Reassuringly, the authors report finding that, across the specialties, there were high rates of recognition of epinephrine as first-line treatment for anaphylaxis. Interestingly, most emergency medicine providers prescribed scheduled corticosteroids and antihistamines after resolution of anaphylaxis, whereas most allergy/immunology providers did not. This is consistent with the 2015 anaphylaxis practice parameter recommendations, which state that, “H1 and H2 antihistamines or corticosteroids should be considered as optional agents or adjunctive therapy” and that “The expectation that they produce a decrease of biphasic or prolonged reactions is not supported by strong evidence.”⁷ The importance of first-line epinephrine is further emphasized by Kim et al.,⁸ who convened a group of adult and pediatric allergists with the goal of providing an evidence-based expert clinical perspective on how physicians might best tailor epinephrine autoinjector (EAI) selection (device and dosage) to their patients with anaphylaxis. The authors found that personalized EAI selection was influenced by intrinsic individual factors as well as extrinsic factors, such as the properties of the individual EAI (e.g., dose, needle length, overall design); however, an unmet need was identified in that there currently are no EAIs with customizable dose and needle length. The important role of the allergist in the long-term management of anaphylaxis is the focus of a literature review by Navalpakam et al.,⁹ who outlines the allergist's responsibilities as identifying risk factors, instructing on allergen avoidance, prevention of recurrences, and patient education.

Completing this tetrad on anaphylaxis is this issue's Patient-Oriented Problem Solving (POPS) case presentation that explores the differential diagnosis and evaluation of anaphylaxis in a 62-year-old woman who received a cardiac transplantation from a nonatopic donor. 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 allergist/immunologist in-training by using a didactic format of clinical presentation and deductive reasoning. In this issue's POPS, Zhang et al.¹⁰ from the Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, lead the reader through this learning process, which illustrates 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.

One article in this issue addresses the clinical utility of molecular allergy diagnostics. In an effort to reduce the need for oral food challenges, Nieminen et al.¹¹ used molecular diagnostics to determine serum sIgE cutoff levels for cow's milk allergens in predicting oral milk challenge outcomes in children with suspected cow's milk allergy. They studied 135 Finnish children with suspected cow's milk allergy who underwent open oral food challenge with unheated cow's milk. sIgE levels to milk (f2), casein (Bos d 8), alpha lactalbumin (Bos d 4), beta lactoglobulin (Bos d 5), and bovine serum albumin (Bos d 6) were measured by using SIgE and compared with the challenge outcomes. They identified age-dependent levels of milk serum sIgE that were >90% specific for positive food challenge; however, the authors found that no individual allergen sIgE had a better area under the curve than milk. They conclude that molecular allergy diagnostics did not improve the predictive performance compared with milk sIgE.

Transitioning to the topic of chronic urticaria, Do et al.¹² provide a review of current literature on standard and novel therapeutics in the management of chronic urticaria. The authors not only report that second-generation antihistamines, omalizumab, and cyclosporine continue to provide the most proven therapeutic options but also review the status of ongoing clinical trials using dupilumab, mepolizumab, benralizumab, tezepelumab, and CDX-0159 biologics. Because of the importance of this information to patients who have this condition, it was chosen as the basis for this issue's “For the Patient” section entitled “Chronic urticaria: New treatment options.” This segment, found in the final pages of the print version of this issue and also available online, consists of a one-page article synopsis written in a readily comprehensible fashion to help patients better understand the content of the full article.

In summary, the collection of articles found within the pages of this issue provides further insight into the intersecting crossroads of inflammation and disease that manifest as allergic, immunologic, and respiratory disorders that afflict patients whom the allergist/immunologist serves. The articles in this issue exemplify how the complexities of allergic disease pathogenesis and development continue to challenge the allergist/immunologist. In keeping with the overall mission of the Proceedings, which is to distribute timely information with regard to 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 continue to foster enhanced patient management and outcomes. On behalf of the Editorial Board, we hope that you are able to make practical use of the diversity of literature offered in this issue of the Proceedings.