Nasal allergen challenge (NAC): Practical aspects and applications from an EU/US perspective-a Work Group Report of the AAAAI Rhinitis, Rhinosinusitis and Ocular Allergy Committee.

Nasal allergen challenge (NAC) is applied in a variety of settings (research centers, specialty clinics, and hospitals) as a useful diagnostic and research tool. NAC is indicated for diagnosis of seasonal and perennial allergic rhinitis, local allergic rhinitis, and occupational rhinitis; to design the composition of allergen immunotherapy in patients who are polysensitized; and to investigate the physio-pathological mechanisms of nasal diseases. NAC is currently a safe and reproducible technique, although it is time- and resource-consuming. NAC can be performed by a variety of methods, but the lack of a uniform technique for performing and recording the outcomes represents a challenge for those considering NAC as a clinical tool in the office. The availability of standardized allergens for NAC is also different in each country. The objective of this workgroup report is to review the current information about NAC, focusing on the practical aspects and application for diagnosis of difficult rhinitis phenotypes (eg, local allergic rhinitis, occupational rhinitis), taking into account the particular context of practice in the United States and the European Union.

Consensus report from the Food Allergy Research & Education (FARE) 2019 Oral Immunotherapy for Food Allergy Summit.

Food allergy is a major health problem affecting 5% to 10% of the population in developed nations, including an estimated 32 million Americans. Despite the large number of patients suffering from food allergies, up until the end of January 2020, no treatment for food allergies had been approved by the US Food and Drug Administration. The only options were avoidance of food allergen triggers and acute management of allergic reactions. A considerable body of data exists supporting oral immunotherapy (OIT) as a promising, novel treatment option, including that for the now Food and Drug Administration-approved peanut OIT product Palforzia (Aimmune Therapeutics, Brisbane, Calif). However, data for long-term quality-of-life improvement with OIT varies, depending on the measures used for analysis. Like many therapies, OIT is not without potential harms, and burdens, and the evaluation of patient-specific risk-benefit ratio of food OIT produces challenges for clinicians and patients alike, with many unanswered questions. Food Allergy Research & Education organized the Oral Immunotherapy for Food Allergy Summit on November 6, 2019, modeled after the PRACTALL sessions between the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology to address these critical issues. Health care providers, patient representatives, researchers, regulators, and food allergy advocates came together to discuss OIT and identify areas of common ground as well as gaps in existing research and areas of uncertainty and disagreement. The purpose of this article was to summarize that discussion and facilitate collaboration among clinicians and patients to help them make better-informed decisions about offering and accepting OIT, respectively, as a therapeutic option.

Nasal and ocular challenges.

Nasal and ocular challenges facilitate the evaluation of subjective and objective responses to defined allergen or irritant exposure. Nasal and ocular allergen challenges are the gold standard to diagnose allergic rhinitis and conjunctivitis, respectively, and aid in the evaluation of novel therapies in clinical trials. Additionally, nasal and ocular allergen challenges might help identify medically relevant allergens in clinical practice. Nonspecific or irritant challenges evaluate mucosal hyperreactivity. Direct mucosal challenges, which can be performed in an office or research setting, expose the participant to higher allergen doses than common in the natural environment. Park studies and environmental chambers, which are most practical in clinical trials, more closely simulate natural allergen exposure. International consensus guidelines for nasal and ocular challenges do not exist. Therefore the positivity criteria, methodologies, and extract or allergen preparations used in challenges vary in the literature. Regardless of these limitations, nasal and ocular challenges are helpful clinical and research tools for nasal and ocular diseases.

Asthma and chronic obstructive pulmonary disease inhalers: Techniques for proper use.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) affect millions of Americans. Inhalers are necessary to manage these diseases, but physicians and patients often struggle to use them correctly. OBJECTIVE: To simplify inhaler use for patients and physicians. METHODS: This article compares the various inhalers used to treat asthma and COPD, their techniques for use, and the steps necessary to prime the inhaler if required. The authors provide a suggested standardized technique for the use of metered-dose inhalers, dry powder inhalers, and soft-mist inhalers to provide for a more universal approach for the use of these medications and summarizes how each product is to be used per the U.S. Food and Drug Administration approved package insert. RESULTS AND CONCLUSIONS: The simplified techniques proposed in this article for the use of metered-dose inhalers, dry powder inhalers, and soft mist inhalers used to treat asthma and COPD may limit inhaler misuse and aid in proper medication delivery and treatment.

Aortoduodenal fistula in a patient on intravitreal bevacizumab injections: a case report.

An 88-year-old woman on long-term intravitreal bevacizumab presented with acute gastrointestinal hemorrhage. She was stabilized and underwent nonrevealing upper endoscopy. She continued to require intermittent blood transfusions, and resulting computed tomography of the abdomen revealed an aortoduodenal fistula. The patient was undergoing treatment for her macular degeneration with intravitreal bevacizumab, an angiogenesis inhibitor frequently used to treat solid organ malignancies. Systemic administration has been associated with serious adverse events, including gastrointestinal hemorrhage, perforation, and fistula formation. Intravitreal bevacizumab has been used off-label to treat macular degeneration, but data on the safety of this therapy are limited. Given her lack of other risk factors, the authors postulate a potential association between intravitreal bevacizumab and aortoduodenal fistula formation in this patient.

Anaphylaxis: Access to Epinephrine in Outpatient Setting.

Epinephrine is a lifesaving medication to treat systemic allergic reactions including anaphylaxis. Epinephrine autoinjectors (EAIs) are expensive, not available everywhere in the world, and shortages can limit their access. Epinephrine prefilled syringes and epinephrine kits are lower-cost alternatives to EAIs. Advantages, disadvantages, and costs of available products are discussed and the socioeconomic factors impacting access to EAIs described. EAIs designed for infants also are discussed.

Emerging developments in the forefront of peanut oral immunotherapy.

PURPOSE OF REVIEW: Despite the COVID-19 pandemic, progress continued in the field of peanut oral immunotherapy over the past 12 to 18 months. Of importance, the first oral immunotherapy product for the treatment of peanut allergy was approved by the US Food and Drug Administration in January 2020. RECENT FINDINGS: Suggested modifications to the practice of oral immunotherapy, some of which may have lasting impacts, were circulated as a result of the pandemic. New advances in pathophysiology, sustained unresponsiveness, quality of life, safety, and cost effectiveness were also published. SUMMARY: During 2020, COVID-19 influenced the daily practice of allergy and immunology, with peanut oral immunotherapy being no exception. However, clinicians now have a FDA-approved treatment option for peanut allergy in children, a welcome development for a difficult disease. Future research is needed to clarify several knowledge deficits surrounding the best use of peanut OIT.

How to Assess Effectiveness of Biologics for Asthma and What Steps to Take When There Is Not Benefit.

Five biologic medications are approved in the United States for the treatment of asthma that is not well controlled with other therapies. All target asthma with elevated type 2 inflammatory markers, such as elevated eosinophils, fractional exhaled nitric oxide, or total and specific IgE. Asthma severity, phenotype, age, biomarkers, treatment goals/outcomes, comorbid conditions, safety, and cost should all help guide the initial biologic choice. In addition, a shared decision-making process with the patient is needed to optimize adherence, with special attention to patient preference regarding outcomes, safety concerns, and medication administration options. After a biologic agent is initiated, sufficient time is needed to monitor efficacy and response. For patients who do not respond favorably, patient-, disease-, and medication-related factors should be considered and remedied, if possible. Persistent suboptimal responders necessitate a reexamination of asthma phenotype, biomarkers, and the suspected immune response pathways. For some patients, a change in biologic therapy or other therapeutic options may be warranted. In this review, we examine the clinical approach for choosing an initial biologic for the treatment of asthma, the assessment of response to biologics, and the process of troubleshooting and adjusting biologic treatment for those patients with suboptimal responses.

Economic considerations in the treatment of systemic allergic reactions.

Epinephrine is a life-saving medication used to treat systemic allergic reactions including anaphylaxis. Epinephrine autoinjectors (EAIs) are expensive and worldwide availability is limited. Epinephrine prefilled syringes and epinephrine kits are potentially lower-cost alternatives to EAIs. Advantages, disadvantages, and costs of available products are discussed. The socioeconomic factors impacting access to EAIs are described.

Effects of Exposure to New Car Interiors in Patients With Asthma and Allergic Rhinitis.

RATIONALE: Vehicle interiors are an important microenvironment for atopic subjects. This study evaluated the subjective and objective physiologic and clinical effects of exposing subjects with asthma and allergic rhinitis to new 2017 Mercedes vehicles during 90-minute rides. METHODS: Ten adult asthmatics with allergic rhinitis were assessed before and 45 and 90 minutes into rides in a 2017 Mercedes-Benz S-Class sedan and GLE-Class SUV on 2 separate days. Assessments included spirometry, fractional exhaled nitric oxide, peak nasal inspiratory flow, asthma symptom scores, and physical examinations. RESULTS: Of the 10 subjects, 6 were women, mean age was 32 years, and 6 and 4 were using chronic asthma controllers or intranasal corticosteroids, respectively. None of the subjects had worsening of asthma or rhinitis symptoms during the rides. There were no statistically significant changes from baseline in forced expiratory volume in 1 second, forced expiratory volume in 1 second:forced vital capacity ratio, forced expiratory flow at 25%-75% of vital capacity, fractional exhaled nitric oxide, or peak nasal inspiratory flow at 45 or 90 minutes into the rides with either Mercedes vehicle (all P values > .1 using generalized linear mixed model). CONCLUSION: The interior environment of the tested Mercedes vehicles did not cause changes in subjective or objective measures of asthma and allergic rhinitis. We suggest that this model system can be used to test other vehicles for putatively adverse effects on patients with allergic respiratory disorders.

The High Cost of Epinephrine Autoinjectors and Possible Alternatives.

Epinephrine autoinjectors provide potentially life-saving therapy for pediatric and adult subjects with systemic allergic reactions, including anaphylaxis. However, the cost of these devices, specifically the EpiPen (Mylan, Canonsburg, Pa), is increasing exponentially. Epinephrine autoinjectors are commonly prescribed in the United States but are not readily available worldwide. Alternatives for the self-administration of epinephrine exist and should be considered for patients who cannot afford or do not have access to these devices. The epinephrine prefilled syringe, stored in an eyeglass or pencil case, is a safe and viable option for the self-administration of epinephrine. Epinephrine prefilled syringes may not be as ideal as using autoinjectors but are superior to patients living without access to this medication.

Sublingual Immunotherapy for the Polyallergic Patient.

Allergen immunotherapy is the only disease-modifying treatment for allergic diseases. Sublingual immunotherapy (SLIT) in liquid and tablet form has been used by clinicians in Europe for years, but has only recently gained popularity and approval in the United States. In 2014, the US Food and Drug Administration approved 3 SLIT tablets for the treatment of allergic rhinitis, with or without allergic conjunctivitis. Immunotherapy treatment strategies for the polysensitized patient vary between the United States and Europe. This variation hinges upon whether the polysensitized patient is truly polyallergic. Polysensitization is the positive response to 2 or more allergens on skin prick testing or in vitro specific-IgE testing. Polyallergy is the symptomatic clinical response to 2 or more allergens. In this review, we discuss the use of SLIT in the United States with a focus on treating the polyallergic patient with SLIT.

Benralizumab for the treatment of asthma.

INTRODUCTION: The classification of asthma into phenotypes and endotoypes allows for the use of targeted therapies, including three biologics which target interleukin 5 (IL-5) signaling in eosinophilic asthma. Areas covered: As of December 2016, two monoclonal antibodies, mepolizumab and reslizumab, are approved by U.S. Food and Drug Administration and one, benralizumab, is in clinical development. Two phase 3 trials for benralizumab, SIROCCO and CALIMA, were published in September 2016. Although there are no direct comparisons among these three anti-IL-5 therapies, the goal of this review is to summarize the current data and discuss their potential similarities and differences, with a focus on benralizumab. Expert commentary: Compared to mepolizumab and reslizumab, the possible advantages of benralizumab are less frequent dosing and a potential to reduce exacerbations irrespective of the blood eosinophil count. Some improvements in asthma symptom scores and quality of life occur with all three biologics, but the clinical meaningfulness of these improvements is less clear. A more defined reference range for eosinophil levels is necessary to determine which subjects will best benefit from these medications. Until quality randomized controlled trials directly compare the three, choosing among them for the treatment of eosinophilic asthma remains difficult.

Biologic Therapy and Novel Molecular Targets of Severe Asthma.

Treatment options for severe or uncontrolled asthma are increasing, especially pertaining to novel biologic therapies. The 2 primary asthma endotypes, T2 high and T2 low, are defined by the level of type 2 T helper and innate lymphoid cell activity and mediators. Most therapies for severe asthma target T2 high asthma, including the 3 biologics approved for use in the United States and Europe: omalizumb, mepolizumb, and reslizumab. Other biologics, with various molecular targets, are under investigation. Unfortunately, treatment options for T2 low asthma are limited. Although these therapies may improve asthma symptoms, exacerbation rates, and lung function parameters, they have not been shown to modify the disease process or provide lasting benefits after discontinuation. Biomarkers identified thus far to help guide individualized therapy in severe asthma are helpful, but imperfect discriminators for picking the best option for individual patients. This review will discuss the mechanisms of action, indications, and therapeutic effects of currently available and emerging biologics for the treatment of severe or uncontrolled asthma.

Individualized Treatment of Allergic Rhinitis According to Nasal Cytology.

PURPOSE: Nasal cytology is important in the diagnosis and treatment of nasal inflammatory diseases. Treatment of allergic rhinitis (AR) according to nasal cytology has not been fully studied. We plan to explore the individualized treatment of AR according to nasal cytology. METHODS: Nasal cytology from 468 AR patients was examined for inflammatory cell quantity (grade 0-5) and the percentage of neutrophils and eosinophils. Results were subdivided into the following categories: AR(Eos), eosinophil ≥50% of the whole inflammatory cells; AR(Neu), neutrophils ≥90%; AR(Eos/Neu), 10%≤ eosinophil <50%; AR(Low), grade 0/1 inflammatory cell quantity. Nasal cytology-guided treatment was implemented: all AR(Eos) patients (n=22) and half of the AR(Neu) patients (AR[Neu1], n=22) were treated with mometasone furoate spray and oral loratadine. Another half of the AR(Neu) patients (AR[Neu2], n=22) were treated with oral clarithromycin. Visual analog scale (VAS), symptom scores, and nasal cytology were evaluated 2 weeks before and after treatment. RESULTS: There were 224/468 (47.86%) AR(Eos), 67/468 (14.32%) AR(Neu), 112/468 (23.93%) AR(Eos/Neu), and 65/468 (13.89%) AR(Low) of the AR patients studied. There were no significant differences in clinical characteristics among these subgroups, except that the nasal blockage score was higher in AR(Eos) patients than in AR(Neu) patients (1.99 vs 1.50, P=0.02). Comparing AR(Eos) patients with AR(Neu1) patients 2 weeks after treatment, nasal symptoms and VAS were significantly lower in AR(Eos) patients, except for nasal blockage symptoms (P<0.05 of nasal itching and sneezing; P<0.01 for nasal secretion, total scores, and VAS). Comparing AR(Neu1) with AR(Neu2) patients, nasal symptoms, and VAS were significantly lower in AR(Neu2), except for nasal blockage and nasal itching symptoms (P<0.05 for nasal secretions, sneezing, total score, and VAS). CONCLUSIONS: Nasal cytology may have important value in subtyping AR and optimizing AR treatment. Treating neutrophils is very important in AR patients with locally predominant neutrophils.

Debunking myths about "allergy" to radiocontrast media in an academic institution.

PURPOSE: Patients with "allergy" to iodine and shellfish often do not obtain necessary radiologic procedures due to anxiety about potential radiocontrast media reactions. This study assesses the impact of an educational intervention to dispel these myths. METHODS: The authors surveyed 252 internal medicine, emergency medicine, pediatrics, radiology, obstetrics/gynecology, and surgery health professionals before and after an educational intervention. Pre- and posttest responses were analyzed to assess the impact of the intervention on beliefs about radiocontrast media reactions and their perceived relationship to shellfish allergy and iodine "allergy." RESULTS: The mean pre- and posttest correct response scores were 41% and 91%, respectively. The intervention had a greater impact on respondents' knowledge about iodine allergy than shellfish allergy, most likely due to the difference in baseline knowledge (P < 0.005). Emergency medicine garnered the highest pretest correct response score (54%). Internal medicine earned the lowest pretest score (30%). There was a significant difference between the highest and lowest scoring specialties on the pretest (P = 0.037). There was no statistically significant correlation with training levels. There was a considerable decrease in the percentage of respondents who would withhold radiologic studies from patients suspected of shellfish or iodine allergy. The percentage of respondents who would premedicate patients with antihistamines or steroids also decreased significantly. CONCLUSION: An educational intervention helps rectify misconceptions among health care professionals about radiocontrast media reactions and their perceived relationship to shellfish or iodine allergy.