Dose-dependent association between inhaled corticosteroid use and risk of obesity and metabolic syndrome in asthma.

Background: Inhaled corticosteroids (ICS) are widely prescribed medications. Some studies have reported that ICS may suppress the hypothalamic-pituitary-adrenal axis and induce systemic effects. Objective: To explore the possibility of a dose-dependent association between the long-term use of ICS and the risk of obesity and other markers of metabolic syndrome. Methods: A 5-year retrospective two-arm cohort study explored patients on asthma and not on ICS relative to patients with asthma who were on varying doses of ICS (low, medium, and high) and attributes such as body mass index (BMI) trajectory and prescription of antihypertensive, antidiabetic, and cholesterol-lowering medications. Results: A total of 229 subjects with asthma were in the control cohort, and 215 subjects with asthma were in the ICS cohort. The ICS cohort was subdivided into individuals on low- (n = 88), medium- (n = 107), or high- (n = 20) dose ICS throughout the 5-year study period. For every 1-year increase in time, the BMI in the high-dose ICS group increased at a rate of 0.25 kg/m² when compared with the subjects in the control group after controlling for age and gender. Also, for every 1-year increase in time, the BMI of those on medium-dose ICS increased by 0.06 kg/m² compared with those in the control group after controlling for age and gender. The subjects on ICS also had a statistically increased risk of being prescribed antihypertensive, antidiabetic, and cholesterol-lowering medications. Conclusion: ICS use in the subjects with asthma was associated with a dose-dependent risk of increasing BMI trajectories over time and an increased requirement for antidiabetic and cholesterol-lowering medications. One possible conclusion from this study is that long-term medium- and high-dose ICS have the potential to induce systemic effects.

Appraisal of the Real-World Effectiveness of Biologic Therapies in Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: There are no head-to-head studies for patients with aspirin-exacerbated respiratory disease (AERD) comparing any of the 5 Food and Drug Administration-approved respiratory biologic therapies. OBJECTIVE: Explore outcomes in subjects with AERD using biologic therapies in a real-world clinic setting. METHODS: A retrospective pilot study was conducted for subjects with AERD who had been prescribed omalizumab (anti-IgE), mepolizumab (anti-IL-5), reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor alpha [anti-IL-5Rα]), or dupilumab (anti-IL-4 receptor alpha [anti-IL-4Rα]). Clinical outcomes pre- versus postinitiation of biologic therapy were explored including symptoms, 22-item sino-nasal outcome test scores, systemic corticosteroid and antibiotic prescriptions, and emergency room visits related to AERD. RESULTS: Of the 74 subjects, 58.1% (n = 43) had used 1 biologic, though many (41.9%, n = 31) trialed more than 1 biologic. Of the 50 subjects who had used anti-IL-4Rα therapy, 98% (49 of 50) still had this therapy prescribed at study completion compared with 48.6% (17 of 35) and 26.9% (7 of 26) of those who used anti-IgE and anti-IL-5 and anti-IL-5 receptor alpha (anti-IL-5/IL-5Rα) therapy, respectively. Among those on anti-IL-4Rα therapy, there was a significant reduction in median total 22-item sino-nasal outcome test scores (51 to 19, P = .0002), corticosteroid bursts (2 to 0, P < .0001), and median number of antibiotic courses for respiratory disease (1 to 0, P = .0469) prebiologic versus postbiologic initiation. No statistically significant difference in those outcomes was observed for individuals on anti-IgE or anti-IL-5/IL-5Rα therapy. CONCLUSIONS: Anti-IL-4Rα therapy led to significantly higher rates of clinical improvement in AERD when compared with anti-IL-5/IL-5Rα and anti-IgE biologic therapies. Prospective studies would help clarify best practices for the use of biologic therapies in AERD.

The first reported case of Blaptica dubia cockroach allergy.

BACKGROUND: Periplaneta americana and Blattella germanica cockroaches are widespread, and risk of sensitization increases in urban environments where these roaches thrive as household pests. There are no prior reports of Blaptica dubia cockroach allergy, though human exposure to B. dubia is increasing through commercial breeding as feeder insects. CASE PRESENTATION: A 50-year-old B. dubia cockroach breeder presented with progressively worsening upper and lower respiratory symptoms in recent years. Symptoms were worse with exposure to her B. dubia roach colony. Skin prick testing (SPT) to B. dubia cast skin, internal organs, and feces was performed in both the subject and a human control. Testing for P. americana and B. germanica sensitization was also performed in the subject. SDS-Polyacrylamide gel electrophoresis (PAGE), immunoblots, and enzyme-linked immunosorbent assays (ELISA) studies were performed using the subject and control serums to explore for specific IgE binding to B. dubia as well as P. americana. Our results showed SPT was positive to B. dubia internal organs in the subject and negative in the control. In the subject, SPT was negative to P. americana though intradermal (ID) testing was positive and serum specific IgE (sIgE) testing was negative to B. germanica. Immunoblotting of the subject's serum to B. dubia internal organ extract showed several distinct bands of IgE binding at 47 kilodaltons (kD), 68 kD, 74 kD, 83 kD, and 118 kD. The strongest band was at 118 kD on B. dubia immunoblotting, which was absent in P. americana on SDS-PAGE. ELISA studies showed an increased IgE response to both B. dubia and P. americana in the subject versus the control. CONCLUSIONS: This case confirmed the first reported allergy to B. dubia cockroaches. There may be cross-reactivity between B. dubia and P. americana, though our case suggests SPT and sIgE testing using P. americana and B. germanica extract has potential to miss a B. dubia cockroach allergy. This allergy is likely underreported, and further study is needed to explore the natural history of B. dubia cockroach allergy.

Provider recommendations and maternal practices when providing breast milk to children with immunoglobulin E-mediated food allergy.

BACKGROUND: There is limited research investigating maternal dietary practices and health care provider recommendations when providing breast milk (BM) to children with immunoglobulin (Ig) E-mediated food allergy. OBJECTIVE: To explore health care provider recommendations and maternal practices when providing BM to children with IgE-mediated food allergy and to assess for possible IgE-mediated reactions to BM while the mother consumed the food to which her child has allergy. METHODS: A web-based survey was distributed to breastfeeding (BF) mothers of children with IgE-mediated food allergies. Reported reactions to BM were scored by an allergist, provided only with the details of the possible reaction and not the suspect allergen or route of exposure, as to the likelihood that the reaction was IgE mediated. RESULTS: A total of 133 mothers completed the survey. After food allergy diagnosis, 47.4% (n = 63) of the mothers reported that they were advised by their health care provider to continue BF without dietary restriction, 17.3% (n = 23) were advised to avoid eating the food(s) their child has allergy to while BF, and in 28.6% (n = 38), this concern was not addressed. A few of the mothers (12%, 16/133) reported that their child experienced an allergic reaction to BM. An allergist evaluated most of these reactions (75%, 12/16) as not likely IgE mediated. CONCLUSION: This study exposed inconsistent recommendations for mothers providing BM to children with IgE-mediated food allergies. Most mothers were able to consume the food their child has allergy to without adverse sequelae. Standardized, evidence-based recommendations would enhance the well-being of these mother-infant dyads.

Primary immunodeficiency diseases treated with immunoglobulin and associated comorbidities.

Background: Primary immunodeficiency diseases (PIDD) consist of a heterogeneous group of disorders characterized by various aspects of immune dysregulation. Although the most universally recognized manifestation of PIDD is an increased susceptibility to infections, there is a growing body of evidence that patients with PIDD often have a higher incidence of lung disease, autoimmunity, autoinflammatory disorders, and malignancy. Objective: The purpose of this study was to better understand the noninfectious complications of PIDD by determining the comorbid disease prevalence across various age groups, genders, and immunoglobulin replacement types compared with the general population. Methods: A large U.S. insurance claims database was retrospectively analyzed for patients who had a diagnosis of PIDD and who had received intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG). The prevalences of 31 different comorbid conditions in the Elixhauser comorbidity index were compared among the 3125 patients in the PIDD population to > 37 million controls separated by gender and by 10-year age cohorts. Results: In the PIDD population, statistically significantly higher comorbid diagnoses included chronic obstructive pulmonary disease-asthma in 51.5%, rheumatoid disease in 14%, deficiency anemia in 11.8%, hypothyroidism in 21.2%, lymphoma in 16.7%, neurologic disorders in 9.7%, arrhythmias in 19.9%, electrolyte disorders in 23.6%, coagulopathies in 16.9%, and weight loss in 8.4%. Conclusion: PIDD that require immunoglobulin replacement are associated with an increased risk of numerous comorbid conditions that affect morbidity and mortality. Recognition and increased awareness of these noninfectious complications can allow for better monitoring, care coordination, targeted treatments, and improved prognosis.

Choice of biologics in asthma endotypes.

PURPOSE OF REVIEW: The aim of this study was to highlight the phenotypes and endotypes of asthma as a tool for selection of the Food and Drug Administration approved biologic therapies. RECENT FINDINGS: An evolving concept of asthma has led to the identification of distinct phenotypes and endotypes in this disease. Asthma endotypes are defined as the biological mechanism and are often categorized as T2-high and T2-low based on the influence of T helper type 2 (T2) cells and type 2 cytokines, including interleukin (IL)-4, IL-5, IL-9 and IL-13. Biomarkers such as peripheral blood absolute eosinophil count, total IgE, specific IgE and fractional exhaled nitric oxide may be used as indicators of asthma endotypes and help predict response to biologic therapies. There are currently five biologic therapies approved as a treatment option for T2-high asthma: omalizumab, benralizumab, mepolizumab, reslizumab and dupilumab. SUMMARY: Here, we explore the current understandings of asthma endotypes and review their associated phenotypes. We provide practical and evidence-based guidance for clinicians considering a biologic for asthma add-on maintenance therapy.

Allergy/Immunology Trainee Experiences During the COVID-19 Pandemic: AAAAI Work Group Report of the Fellows-in-Training Committee.

As a result of the coronavirus disease 2019 (COVID-19) global pandemic, medical trainees have faced unique challenges and uncertainties. To capture the experiences of allergy and immunology fellows throughout the United States and Canada during this time, a 17-item electronic questionnaire was distributed to 380 fellow-in-training (FIT) members of the American Academy of Allergy, Asthma, and Immunology enrolled in US and Canadian allergy/immunology fellowship programs. Voluntary and anonymous responses were collected from April 15 to May 15, 2020. In addition to summary statistics, categorical data were compared using χ2 tests (Fisher's exact). Responses were obtained from FITs across all years of training and primary specialties (Internal Medicine, Pediatrics, and Medicine-Pediatrics) with a response rate of 32.6% (124 of 380). Reassignment to COVID-19 clinical responsibilities was reported by 12% (15 of 124) of FITs, with the largest proportion in the US northeast region. A majority of FITs used telehealth (95%) and virtual learning (82%) during the pandemic. Overall, 21% (25 of 120) of FITs expressed concern about potentially lacking clinical experience for independently practicing allergy and immunology. However, FITs using telehealth reported lower concern compared with those who did not (18.4% [21 of 114] vs 66.7% [4 of 6]; P = .01). The survey shows that allergy and immunology trainee experiences have varied considerably since the COVID-19 outbreak. Notably, the adoption of telehealth and virtual learning was commonly reported, and optimization of these virtual experiences will be helpful. Even outside of pandemics, training on the use of telemedicine may be a sound strategy in preparation for future health care delivery and unexpected events.

Adverse reactions to food additives.

Food additives are naturally occurring or synthetic substances that are added to food to modify the color, taste, texture, stability, or other characteristics of foods. These additives are ubiquitous in the food that we consume on a daily basis and, therefore, have been the subject of much scrutiny about possible reactions. Despite these concerns, the overall prevalence of food additive reactions is 1-2%, with a minority of the wide variety of symptoms attributed to food-additive exposure being reproduced by double-blind placebo controlled challenges. Reactions can be broadly classified into either immunoglobulin E (IgE)- and non-IgE-mediated reactions, with natural additives accounting for most IgE-mediated reactions, and both natural and synthetic additives being implicated in the non-IgE-mediated reactions. Reactions that include asthma exacerbations, urticaria and/or angioedema, or anaphylaxis with ingestion of a food additive are most deserving of further allergy evaluation. In this article, we discussed the different types of adverse reactions that have been described to various food additives. We also reviewed the specifics of how to evaluate and diagnose a food additive allergy in a clinic setting.

Aspirin-exacerbated respiratory disease.

Aspirin-exacerbated respiratory disease (AERD) classically presents with severe asthma, nasal polyposis, and respiratory exacerbations in response to cyclooxygenase (COX)-1 inhibition. Recent advances in our understanding of AERD have revealed multiple facets of immune dysregulation, including diminished prostaglandin E2 (PGE2) function and elevated levels of both cysteinyl leukotrienes (CysLTs) and innate cytokines such as interleukin 33 (IL-33). Inflammatory mediators in AERD heighten the recruitment and activation of innate lymphoid cells type 2 (ILC2), mast cells, eosinophils, and platelet-adherent leukocytes. This contributes to a cyclical pattern of type 2 inflammation. Here, we highlight current understanding of the immunopathogenesis of AERD.

Evaluation of long-term course in children with eosinophilic esophagitis reveals distinct histologic patterns and clinical characteristics.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic and increasingly prevalent antigen-driven disease. There is a paucity of information on long-term course in children. OBJECTIVE: We sought to understand the longitudinal trajectory of pediatric EoE during routine clinical care. METHODS: We prospectively enrolled children into an EoE database and reviewed their medical and pathologic records over 13 years. RESULTS: From 2011 to 2015, 146 children with EoE seen for their first visit at our center had 2 or more years of follow-up and 3 or more endoscopies over an average follow-up period of 5.13 years (range, 2-13 years). Longitudinal eosinophilic inflammation during treatment demonstrated 3 patterns over time. Children with less than 15 eosinophils/high-power field (hpf) for greater than 75% of their follow-up period were termed continuous responders (CRs). Children with waxing and waning inflammation of less than 15 eosinophils/hpf for less than 75% but 25% or more of the follow-up period were termed intermittent responders (IRs). Nonresponders (NRs) were defined as having less than 15 eosinophils/hpf for less than 25% of their follow-up. Fifty-nine (40%) of 146 patients were CRs, 65 (45%) of 146 were IRs, and 22 (15%) of 146 were NRs. CRs differed from IRs and NRs on the parameter of male/female ratio (1:1 in CRs, 4:1 in IRs, and 6:1 in NRs; P < .001) and in their initial response to any therapy, including proton pump inhibitors (P < .001). Endoscopic severity correlated with esophageal eosinophilia (r = 0.73, P < .001). On multivariate analysis, female sex and initial therapeutic response to medications or elimination diet were associated with long-term control of esophageal eosinophilia. CONCLUSIONS: Long-term pediatric EoE followed 3 different longitudinal trajectories of inflammation. The long-term histologic groups differed significantly in biological sex and initial therapeutic response.

A novel autosomal dominant mutation in SOX18 resulting in a fatal case of hypotrichosis-lymphedema-telangiectasia syndrome.

Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is a rare disorder caused by autosomal recessive and autosomal dominant mutations in SOX18. This gene encodes a transcription factor involved in the regulation and development of the human vasculature, lymphatic, and integumentary systems. Individuals with HLTS develop varying degrees of hypotrichosis, lymphedema, and telangiectasias. Other complications, such as renal failure and aortic dilation, have also been observed. Here, we report a neonate with a novel mutation in SOX18 (c.541C>T; p.Gln181stop) presenting with cardinal features of HLTS in addition to unique findings of severe chylothorax and relentless pulmonary hypertension that culminated in death. The purpose of this report is to summarize what is known about this evolving genetic syndrome and to speculate as to how mutations in SOX18 might produce the phenotype.