The continuing “1000 faces of asthma”

In a previous issue of the Proceedings, we dubbed asthma with the term, “a disease of 1000 faces,” because of the wide spectrum of clinical expressions that the many faces of asthma express.¹ True to the moniker, this issue of the Proceedings includes articles that focus on three additional faces of asthma, with topics that range from the risk for asthma development, the effect of perceived stress and/or anxiety, and biologics for oral corticosteroid (OCS) dependent asthma. In the first article, Meireles-Neto et al.² conducted a case-control study in Salvador, Brazil, to determine predictors of asthma development in children with recurrent wheezing during the first three years of life. The subjects included 125 cases and 375 controls; all the subjects were between 6 and 12 years of age.² The authors reported finding that children with a history of ≥3 episodes of wheezing during the first 3 years of life were at least 37 times more likely to develop asthma than children without this history.² A maternal history of asthma and a personal history of atopic rhinitis were also predictors of asthma in children. Because of the importance of this article and its clinically useful implications, it 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 1-page, article synopsis, written in a readily comprehensible fashion to help patients better understand the content of the full article.

To continue with the theme of pediatric asthma, Luria et al.³ conducted a study to characterize the relationship between asthma symptoms and perceived stress and trait anxiety in an adolescent population. They hypothesized that adolescents with asthma may represent a unique population that is particularly vulnerable to perceived stress and anxiety. They found that, among 38 adolescents who reported current asthma, four of six asthma symptom assessments had significant associations based on the Perceived Stress Scale, the most widely used psychological instrument for measuring the perception of stress; these included symptoms of anxiety on awakening, nocturnal awakening due to asthma, activity limitation, and shortness of breath.³ Trait anxiety was measured by using the State-Trait Anxiety Inventory, which demonstrated significant associations with nocturnal awakening and symptoms on awakening. Based on these findings, the authors concluded that asthma symptom severity was associated with increased perceived stress and trait anxiety, and emphasized the importance of considering these factors when providing asthma counseling in the adolescent population.³

In transitioning to one of the most challenging faces of severe asthma to manage, Yilmaz⁴ provided a review of the role of biologic treatments in OCS-dependent asthma. More specifically, he focused on mepolizumab, benralizumab, and dupilumab, three of the currently marketed monoclonal antibody products available for the treatment of asthma. Whereas double-blind placebo controlled studies have demonstrated efficacy and safety with dupilumab in OCS-dependent patient populations, he pointed out that, for reslizumab and omalizumab, similarly designed trials have yet to be reported.⁴ Yilmaz⁴ concludes that biologics are effective in “OCS-dependent asthma” phenotype as add-on therapy but that real-life studies that compare biologics in OCS-dependent severe asthma are urgently needed.

Two articles in this issue deal with the very important issues of patient education and cessation counseling for users of electronic cigarettes (e-cigarettes) and for cigarette smokers. As the number of patients who use e-cigarettes continues to increase, there is an urgent need for all physicians to be comfortable and knowledgeable about cessation counseling. In this regard, Zhou and Baptist⁵ addressed the question, “How confident and effective are allergists, pulmonologists, and primary care physicians in their practice behavior regarding e-cigarettes?” After completing a survey of 291 physicians, the authors reported finding that allergists lacked sufficient knowledge and confidence in providing education and cessation counseling for e-cigarette users.⁵ On a closely related topic, Bobrowska-Korzeniowska et al.⁶ studied the effectiveness of ongoing “face-to-face” anti-tobacco intervention for smoking parents of children with asthma in comparison with simply providing educational leaflets alone. These authors reported finding that “face-to-face” interventions among family members who smoked were effective and lowered cotinine levels in children with asthma and the number of cigarettes smoked when assessed 3 years later.⁶

Three articles in this issue addressed topics of food allergy, ranging from prevention of peanut allergy; the development of jelly fish allergy; to co-sensitization among shrimp, cockroach, and moth. The 2017 addendum to the National Institute of Allergy and Infectious Diseases (NIAID) guidelines on peanut allergy prevention significantly altered recommendations for patients at risk of developing peanut allergies.⁷ However, it is unknown if primary care physicians are aware or follow these guidelines. Alvarez et al.⁸ developed a survey to assess the knowledge, awareness, and practice behaviors of the NIAID guidelines and distributed it to 605 pediatric, family medicine, and medicine-pediatric residents as well as to attending physicians at two large academic centers. A significant knowledge gap was identified. Primary care providers incorrectly answered one-third of the questions related to the prevention of peanut allergy. The authors concluded that there is an urgent need to develop innovative educational strategies to publicize the NIAID guidelines to improve patient outcomes.

In transitioning from peanut to a more exotic food, Amato et al.⁹ reviewed the published literature that chronicles anaphylaxis associated with jellyfish. Although anaphylaxis caused by jellyfish is a rare event, repetitive stings during bathing, as well as during marine sports and occupational exposure, may be an important risk factor that can increase the probability of exhibiting symptoms of sensitization after future contact with or even ingestion of these gelatinous sea creatures. The results of the authors’ Medline (National Library of Medicine, Bethesda, MD) search identified numerous cases that confirmed that dangerous allergic reactions can be caused both by contact and ingestion of jellyfish.⁹

Liao et al.¹⁰ hypothesized that there may be significant co-sensitization between crustacea (shrimp or crab) with moth, cockroach, and dust mite, and performed a study in southern China, where moth is a common allergen. The authors obtained serum samples from 212 patients sensitized to shrimp and tested them for specific immunoglobulin E (IgE) to Dermatophagoides pteronyssinus, crab, cockroach, and moth. High rates of cross-sensitization between moth, D. pteronyssinus, cockroach, and crab were identified among patients sensitized to shrimp, and a strong correlation was found between shrimp, moth, and cockroach sensitization.¹⁰ The authors concluded that shrimp and cockroach co-sensitization might be related to moth allergens, which may contain cross-reacting antigens with these other species.¹⁰

Another topic frequently addressed in previous issues of the Proceedings as well as in the current issue is hereditary angioedema (HAE), a condition that manifests as episodic swelling, most often resulting from deficiency of C1-inhibitor and associated with dysregulation of the contact activation system.^11–25 Currently, there is limited real-world evidence on characteristics of patients with HAE and health-care resource utilization. To help fill this void, Tachdjian et al.²⁶ performed a retrospective cohort study by using data from PharMetrics Plus, an administrative claims data base that includes a large U.S. cohort of adult and pediatric patients who received treatments indicated or used for HAE. The authors report finding substantial burden of attacks, which reflects a need for long-term prophylactic treatments.²⁶

Chronic urticaria (CU) is another topic frequently addressed in previous issues of the Proceedings.^27–36 The urticaria control test (UCT) is a patient-reported outcome measure designed to determine the current level of disease control in patients with CU. Recently, a Brazilian UCT was developed, but its validity and reliability were unknown. Dortas Junior et al.³⁷ conducted a validation study to determine the clinimetric properties of the Brazilian UCT in 130 patients with CU. Based on their findings reported in this issue, they concluded that the Brazilian UCT is a valid and reliable tool for assessing control of CU.³⁷

The presence of IgE, which cross-reacts with allergen components, such as profilins, polcalcins, and cross-reacting carbohydrate determinants (CCD), creates a problem when selecting patients for allergen immunotherapy. Kowal et al.³⁸ sought to evaluate the prevalence of sensitization to profilins, polcalcins, and CCDs in 112 patients from northeastern Poland with seasonal pollen allergic rhinitis. They reported finding that sensitization to rBet v 2/Phl p 12 was demonstrated in 28.6%, to Bet v 4/Phl p 7 in 8.9%, and to CCDs in 25%.³⁸ In 29.3% of the patients, serum IgE reactivity to one or more of the cross-reactive components could be demonstrated.³⁷ Serum IgE reactivity to rBet v 2 was always accompanied by IgE reactivity to rPhl p 12, and IgE reactivity to rBet v 4 was always accompanied by IgE reactivity to rPhl p 7.³⁸ The authors concluded that evaluation of sensitization to cross-reacting components may be useful in the evaluation of patients with pollen allergy who are being assessed for allergen immunotherapy to optimize the constitution of their immunotherapy vaccines.³⁸

This issue’s “Patient-Oriented Problem Solving” (POPS) case presentation explored the differential diagnosis in a 27-year-old man with recurrent sinopulmonary and cutaneous infections. 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, Wu et al.³⁹ from University Hospitals Cleveland Medical Center lead the reader through this learning process, illustrating 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.³⁹

In summary, the collection of articles found within the pages of this issue provides further insight into the intersecting crossroads of genetics and the environment that manifest as the allergic, cutaneous, and respiratory disorders that afflict patients served by the allergist/immunologist. In particular, these articles exemplify how the complexities of asthma, allergic rhinitis, CU, HAE, immunodeficiency, and food allergy 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 help 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.