Peanuta non grata

In diplomacy, a persona non grata (Latin: “person not appreciated”) is a form of exclusion of a foreign person whose entry or domicile in a particular country is prohibited. It is a form of censure directed at individuals inimical to and protective of those more amicable to that country by diplomatic immunity. In a similar way, “peanuta non grata” may be considered a deleterious form of immune response triggered by invasion of an unwelcomed peanut food agent in a subject who is genetically predisposed and supplanting a more tolerable, non-innocuous immune response in an otherwise non-predisposed individual … A.K.A. peanut allergy.

The burden of illness attributable to peanut allergy is of growing concern in the United States. Unfortunately, the only available treatment options for peanut allergy have been limited to avoidance of peanut ingestion, establishment of an individualized acute reaction treatment plan and non–U.S. Food and Drug Administration (FDA) approved peanut oral immunotherapy (POIT). To better understand current peanut allergy management in the United States, Blaiss et al.¹ surveyed 34 allergists and nurse food allergy specialists across the United States, 50% of whom offered their patients self-developed approaches to POIT or offered POIT in clinical studies. The authors reported finding a substantial variability in POIT approaches among practitioners, which they attribute to the absence of an FDA-approved POIT product. Furthermore, all the physicians interviewed expressed a need for effective, FDA-approved, disease-modifying treatments. The future is promising that this unmet need will be addressed in the very near future.

In transitioning from the burden of illness attributable to food allergy to the burden attributable to asthma are four articles in this issue. The burden of asthma is in large part attributable to poor disease control. Sullivan et al.² helps us better understand the factors that affect control by comparing asthma control and medication use among patients with persistent asthma based on whether or not they were allergic. The authors used both a retrospective and prospective analysis of survey responses and medication claims data of patients ages ≥ 12 years and with persistent asthma in a U.S. health maintenance organization. The study subjects were divided into 971 patients with persistent asthma and with evidence of allergy and 312 patients without evidence of allergy.² The authors reported finding that patients with allergy had worse asthma control and greater asthma medication use. They suggested that patients with allergy and with asthma may need more vigilant clinical oversight and treatment management to ensure adequate asthma control. 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 one-page article synopsis, written in a readily comprehensible fashion to help patients better understand the content of the full article.

Another, less well-studied comorbidity, which may contribute to poor asthma control, is depression. Khurana et al.³ sought to evaluate the association between depressive symptoms and markers of asthma control in patients with uncontrolled, severe eosinophilic asthma by means of performing a post hoc analysis of data derived from large clinical trials of mepolizumab in a severe eosinophilic asthma population. These data included the Beck Depression Inventory and a quality-of-life assessment by using the St. George's Respiratory Questionnaire, Asthma Control Questionnaire 5, polypharmacy, and sleep symptoms. The authors reported finding an increased severity of depressive symptoms to be associated with worse respiratory-related quality of life and asthma control in patients with severe eosinophilic asthma.³ Based on the results of their study, the authors suggested a multidimensional approach to management of severe uncontrolled eosinophilic asthma, including timely identification of depressive symptoms.

We shift our focus to the medical treatment of patients with moderate-to-severe uncontrolled eosinophilic asthma, in whom, as reported in this issue, Carr et al.⁴ studied the effect of intravenously administered reslizumab on spirometric lung age (i.e., an expression of lung function relative to chronological age). The authors reported that, in a population of patients with moderate-to-severe inadequately controlled eosinophilic asthma, reslizumab not only reduced lung-age deficit by 5 years but also that these improvements correlated with improved quality of life.⁴ They suggested that, because lung age may serve as a predictive marker of pulmonary function, it could provide a valuable educational tool for patients with asthma.

Reslizumab is one of several new medications known collectively as “biologics,” which have recently become available for the treatment of moderate-to-severe asthma and represent a novel form of precision therapy. Although biologics have well-established efficacy for asthma, other forms of treatment, for example, supplemental therapy with probiotics, have long been advocated and used, yet have unproven effectiveness for the prevention of allergic diseases and asthma. In this issue, Du et al.⁵ helps us understand the potential benefit of probiotic supplementary therapy for asthma, allergic rhinitis, and wheeze by performing a meta-analysis of randomized controlled pediatric trials. The authors reported that, although the administration of probiotics was not associated with risk reduction for the development of asthma compared with controls, subgroup analysis showed enough promise to warrant trials of pre- and postnatal supplementation for the prevention of asthma. Clearly, more randomized controlled trials will be necessary to achieve this goal.

In transitioning from asthma to allergic rhinitis, this issue features a randomized, double-blind, placebo controlled clinical trial that reported the efficacy and safety of a novel combination nasal spray that contained the antihistamine, olopatadine hydrochloride, and the corticosteroid, mometasone furoate (GSP301). In evaluating a total of 1180 patients treated on a twice daily regimen over 14 days, Hampel et al.⁶ reported that GSP301 was efficacious and well tolerated for the treatment of seasonal allergic rhinitis symptoms compared with placebo, with a rapid onset of action (15 minutes) in patients ≥ 12 years of age.

One of the most clinically challenging conditions encountered by the allergist is chronic urticaria. Even among the most effective therapies for this condition, a nonresponse rate will almost always exist, and, for this reason, there is a need for effective predictive markers of response. Omalizumab treatment for chronic urticaria, for example, has well-established efficacy for the treatment of chronic spontaneous urticaria; however, why some patients fail to respond is unknown. To better understand this enigma, Magen et al.⁷ conducted a retrospective, observational study to examine factors related to omalizumab resistance in 106 patients with chronic spontaneous urticaria. They found that 58.9% of the patients had complete remission at 24 weeks of omalizumab therapy (300 mg every 4 weeks), 27.2% had a partial response, and 14.9% of the patients were resistant (reduction of baseline urticaria activity score by <30%).⁷ Factors associated with resistance to treatment were obesity, arterial hypertension, high plasma C3, and high-sensitivity C-reactive protein.

Hereditary angioedema (HAE) has long been a recurring theme in past issues of the Proceedings.^8–21 This issue is no exception because it features two articles on this burdensome and potentially life-threatening condition. In the first article, Valle et al.²² sought to identify HAE in untested first-degree blood relatives of 30 known index patients with HAE caused by a C1-inhibitor deficiency. Fifty previously untested first-degree relatives were identified, and, among these, 30 new cases of HAE were identified. Despite the known family history, the time between the onset of the first symptoms and diagnosis was a mean of 17.8 years. The authors emphasized that screening of family members, including individuals who were asymptomatic, is key for making an earlier diagnosis and establishing effective treatment. In the second HAE article, Li,²³ writing in the “Pearls and Pitfalls” format of the Proceedings, shared his clinical insights regarding the diagnosis of HAE. He pointed out the potential for misdiagnosis when using currently available laboratory diagnostic tools. He advised that physicians should understand the limitations of each assay for judiciously establishing the diagnosis of this life-altering condition.

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 whom the allergist/immunologist serves. In particular, they exemplify how the complexities of food allergy, asthma, allergic rhinitis, chronic urticaria, and HAE continue to challenge the allergist/immunologist. 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 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.