Asthma, allergy, and psychiatric disease

True to the diverse issues that comprise and challenge the field of allergy and immunology, this issue of the Proceedings features a spectrum of articles that, although seemingly disparate and unrelated, focuses on seven major areas of research that coalesce into a cohesive framework that we hope will be of clinical utility for the readership. These are summarized below in the following order: asthma, psychiatric associations of allergic disease, drug allergy, allergic dermatoses, autoimmune associations in allergic disease, rhinitis, and food allergy.

Lang¹ leads off with a timely review of severe asthma, an area of particular interest to clinicians because of the substantial unmet need of morbidity and cost attributable to poor asthma control. Based on his assessment of the literature, Lang¹ suggests a revised paradigm for asthma management that entails categorizing patients with asthma via the use of biomarkers and prescribing mechanism-specific therapy with the goal of achieving improved asthma care outcomes. Biomarkers that Lang¹ discusses include blood eosinophils, sputum eosinophils, periostin, exhaled nitric oxide, and serum immunoglobulin E (IgE).

Extending the knowledge of asthma biomarkers beyond the review by Lang¹ are two additional articles within this issue. The first of these focuses on the antimicrobial proteins of leukocyte granules, which have long been considered as important elements of innate host defense. In recent years, evidence has been accumulating that indicates that some eosinophil granule–derived antimicrobial proteins may also act as chemoattractants for various types of leukocytes. Among these is eosinophil-derived neurotoxin (EDN), which, together with eosinophil cationic protein, belongs to the ribonuclease A (RNase) superfamily. Research regarding EDN and eosinophil cationic protein provides a molecular basis for a better understanding of the links of eosinophils and IgE with asthma. In this vein, Gon et al.² report their efforts to elucidate the correlation between the serum EDN level and markers of severity in adult asthma. They indicate that the serum EDN level may be a useful marker for monitoring persistent airflow limitation in adult patients with allergic asthma who are positive for house-dust–specific IgE antibodies. Also within this issue, Aydın et al.³ report on the potential utility of total serum IgE as a biomarker for responsiveness to omalizumab in patients with allergic bronchopulmonary aspergillosis. They report that patients with allergic bronchopulmonary aspergillosis, characterized by a total IgE level of <1000 IU/mL, seem to be more responsive to omalizumab than those whose total IgE level was >1000 IU/mL.

Variation in therapeutic response to asthma treatment may also be influenced by the route of administration, particularly with inhaled medications. For example, with dry powder inhalers, sufficient inspiratory flow is required to achieve optimal lung deposition. Lores-Obradors et al.⁴ report on the assessment of inspiratory flow in bronchial asthma when using a portable meter. The authors conclude that “before selecting the inhalation system, and especially in older patients and in overweight or sedentary individuals, it is very important to ensure that the inspiratory flow is sufficient to guarantee optimal drug deposition, to improve asthma control and thus patient quality of life.”

Achieving sufficient inspiratory flow requires patient education regarding proper inhaler technique and is but one example of the in-depth understanding of asthma that patients need to acquire. Whether the clinician provides asthma education or the patient self-educates, acquiring asthma knowledge is one of the most important aspects of comprehensive asthma management necessary to achieve optimal asthma outcomes. For self-directed patients, the Internet provides the fastest-growing source of patient-directed asthma education available outside the clinical setting; however, the quality of what is available has not been critically appraised. In this issue, Gonzalez-Estrada et al.⁵ report on their efforts to determine the educational quality of asthma education videos available on YouTube (YouTube, LLC, San Bruno, CA). They found that YouTube asthma videos are generally a poor source of accurate health care information. However, videos by asthma health-care providers were rated highest in quality. They conclude that the allergy/immunology community has a clear opportunity to enhance the value of educational material on YouTube.

As forecasted by the title of this editorial, within the pages of this issue, several articles are presented that focus on the associations of anxiety and depression with asthma and allergies. Li et al.⁶ sought to determine whether anxiety and depression are associated with greater respiratory discomfort in asthma. Through analysis of objective pulmonary function tests, methacholine challenge, and validated questionnaires, they report that anxiety, but not depression symptoms, is associated with greater perceived dyspnea in asthma. In continuing this psychiatric theme, Kõlves et al.⁷ performed a systemic literature review to analyze the existing literature regarding the relationship between allergies and fatal and nonfatal suicidal behaviors. Their results indicate a link between allergies and suicidality, particularly suicide mortality. Comert et al.⁸ investigated the association of patient anxiety with the results of drug tests, together with the other contributing factors. Objective drug tests were performed in conjunction with a validated psychiatric questionnaire. Based on their findings, the authors conclude that patients who experience drug hypersensitivity reactions manifest high levels of anxiety, which, although unrelated to drug allergy test results, can be equally important in patient management.

To continue with drug hypersensitivity reactions, Spriet and Banks⁹ authored a “Pearls and Pitfalls” article that presents an interesting case of recurrent drug reaction with eosinophilia and systemic symptoms, a potentially life-threatening adverse drug reaction important for the clinician to include in the differential diagnosis of adverse reactions to pharmacologic agents. Supplementing the dermatologic theme of this article are an additional four articles that address allergic dermatoses, including atopic dermatitis and angioedema. De Marchi et al.¹⁰ provide novel insight regarding the pathophysiology of atopic dermatitis in their attempt to correlate objective measures of skin barrier impairment (transepidermal water loss and Corneometer) with aeroallergen sensitization. They conclude that patients with atopic dermatitis are affected by barrier function impairment, even on noneczematous skin, and that this defect is associated with greater aeroallergen sensitization. In furthering pathophysiologic research on atopic dermatitis, Tsybikov et al.¹¹ investigated Toll-like receptor (TLR) expression (TLR2 and TLR4 expression) on peripheral blood monocytes during exacerbations of atopic dermatitis and assessed the relationships between TLR expression with atopic dermatitis clinical severity and serum interleukin (IL) 4, IL-10, and IL-17a levels. The authors conclude that peripheral blood CD14⁺ HLA–DR⁺ TLR2⁺ monocytes might have a role in the skewing of a Th 2/Th 17 mediated immune response during flares of atopic dermatitis.

Next, Banerji and Kuhlen¹² provide a review of the ever-increasing advancements in hereditary angioedema, which focuses on the occurrence of this disorder in special populations, viz. children, women of childbearing age, and the elderly. The authors provide clinically useful insights regarding the unique aspects of hereditary angioedema in women with regard to contraception, hormone replacement therapy, pregnancy, lactation, and menopause.

In contrast to hereditary angioedema, idiopathic isolated angioedema is often suspected as being of an autoimmune origin. Karagol et al.¹³ studied the association between thyroid autoimmunity and recurrent angioedema in children. The authors conclude that recurrent, idiopathic, histaminergic, acquired angioedema in children may be related to or associated with autoimmune thyroid diseases; however, the authors were not able to determine whether this association is a causal link or an epiphenomenon. Because of the great interest in the association of autoimmunity and allergic disease, the article by Karagol et al.¹³ was chosen for this issue's “For the Patient” section. 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 and its diagnostic and therapeutic implications. It is printed in a format to allow reproduction on the practitioner's letterhead for distribution to patients.

The association of autoimmunity with allergic disease is also addressed in this issue by Tsybikov et al.¹⁴ who investigated the incidence and role of anticytokine autoantibodies in chronic rhinosinusitis (CRS) with and without nasal polyps. They report that, in patients with CRS, IgA class anticytokine autoantibodies were detected in nasal secretions, with the highest levels of anti–IL-5 and anti–IL-17A anticytokine autoantibodies detected in patients with CRS and with nasal polyps.

In turning the focus from CRS to the disease state of rhinitis, three articles in this issue address this disorder from epidemiologic and therapeutic perspectives. Tseng et al.,¹⁵ in an analysis of a large Taiwanese national insurance claims data set of 1 million enrollees, report finding a decreased risk of acute ischemic stroke in rhinitis. Valerieva et al.¹⁶ performed a double-blind placebo-controlled trial in adults and report on the effect of micronized cellulose powder on the efficacy of topical oxymetazoline in allergic rhinitis. Meltzer and Johnson¹⁷ assessed the objective and subjective benefits and the tolerability of mechanical external nasal dilators in healthy children and in children with nasal congestion due to allergic rhinitis. They report that mechanical external nasal dilators were well tolerated, provided significant objective increases in nasal patency, and reduced subjective nasal airway stuffiness.

In an effort to better understand the changing prevalence of food allergy in adults over the course of the past decade, Verrill et al.¹⁸ analyzed both self-reported and physician-diagnosed food allergy in >4000 U.S. adults who participated in the 2010 U.S. Food and Drug Administration Food Safety Survey. They compared their findings with the prevalence of self-reported food allergy in U.S. adults over the previous decade and found that the prevalence of self-reported food allergy increased among U.S. adults from 2001 to 2010. These results indicate that U.S. adults are increasingly self-reporting food allergies without obtaining a proper medical diagnosis, therefore, which indicates the existence of an unmet need for improved food allergies education.

This issue's “Patient-Oriented Problem Solving” (POPS) case presentation further expands the theme of immunologic food reactions. This recurring feature of the Proceedings, 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, Mourad et al.¹⁹ lead the reader through this process by describing the evaluation of a 17-month-old with severe anemia and respiratory distress. This case report 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.

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.