Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).

Are children with food allergies more likely to have lower urinary tract symptoms? A case-control study.

INTRODUCTION: There are multiple historic reports linking lower urinary tract symptoms (LUTS) in children with food allergies (FA), but contemporary studies are sparse. The objective of this study was to evaluate a potential link between FA and LUTS in the pediatric population. We hypothesized that children with FAs are more likely to have LUTS. MATERIALS AND METHODS: After local IRB approval, pediatric patients (6-17 years [y]) with FAs proven by positive skin prick and/or serum IgE testing were invited to participate. A control group of pediatric patients without FAs was also recruited. All families/legal guardians signed informed consent, and all children signed written assent. Each participant filled out the Vancouver Symptom Score (VSS), a validated questionnaire for dysfunctional elimination syndrome, and the Pediatric Incontinence Questionnaire (PinQ), a validated quality of life assessment for children with bladder dysfunction. Demographic and clinical information were obtained retrospectively. RESULTS: From 2019-2020, 26 children with FAs and 57 without agreed to participate. Mean age was 9.3 y (IQR 7.9 y-13.5 y). There were no differences in gender, age, or race between the two cohorts. There were no significant differences between the two groups in mean VSS score or mean PinQ score. Four children with FAs (15%) and 15 children without (26%) had VSS score ≥ 11 (p = 0.339), indicating dysfunctional elimination. The median PinQ score was 0 (IQR 0-2) in both cohorts. CONCLUSIONS: This study did not identify an association between FAs and LUTS in a population of pediatric patients with laboratory proven FAs.

Differences in oral food challenge reaction severity based on increasing age in a pediatric population.

BACKGROUND: Food allergy reactions range from mild to severe with differences in age appearing to be an important factor associated with reaction severity. OBJECTIVE: To define differences in oral food challenge (OFC) reaction severity in pediatric patients from infancy to adolescence using objective clinical outcomes and standardized reaction grading tools. METHODS: Retrospective review of all positive OFC results at 2 large institutions between September 2016 and February 2019. Reaction severity was defined by presence of cardiovascular, neurologic, lower respiratory, or laryngeal symptoms, epinephrine requirement, and grading using 2 established food allergy reaction scales. RESULTS: Infants and toddlers had fewer reactions involving cardiovascular, neurologic, lower respiratory, or laryngeal symptoms compared with older age groups. Epinephrine was also required less frequently during reactions in infants and toddlers, compared with older age groups. There was no difference in reaction severity in infants and toddlers based on clinical history of eczema. Increasing age was significantly correlated with increased epinephrine requirement (R2 = 0.12, P = .002), elevated Consortium of Food Allergy Research score (R2 = .012, P = .003), and approached significance for increased Practical Allergy score (R2 = .005, P = .05). History of asthma and sesame allergy were identified to be positively correlated with more severe reactions. CONCLUSION: Infants and young toddlers have less severe reactions during OFCs compared with older age groups supporting early food introduction practices. In children under 12 months of age, severe reactions are most rare calling into question screening practices using specific allergy testing before food introduction. Standardized reaction grading tools may be valuable instruments to categorize reaction severity during OFCs.

Maternal Folic Acid Supplementation During Pregnancy and Early Childhood Asthma.

BACKGROUND: Asthma is one of the most common chronic childhood diseases. While folic acid supplementation around conception helps prevent neural tube defects, an animal model suggests that it may be a risk factor for respiratory diseases, although epidemiologic studies have had conflicting results. We investigated the timing of folic acid-containing prescription filling during pregnancy and child asthma. METHODS: In a retrospective cohort study of 104,428 children, born 1996-2005, and their mothers enrolled in Tennessee Medicaid, we investigated the association of filling folic acid-containing prescriptions during pregnancy and childhood asthma at ages 4.5-6 years. We categorized women into exposure groups based on prescription filling centered around the first trimester: no folic acid prescription exposure, exposure in first trimester only, exposure after first trimester, and exposure in first trimester and beyond. We defined asthma using asthma-specific healthcare visits and medication fills. Using logistic regression models, we investigated the relationship adjusting for potential confounders. RESULTS: Overall 15% of children had asthma. Compared with children born to women with no folic acid prescription exposure, children born to women with exposures in the first trimester only or first trimester and later had increased relative odds of asthma (adjusted odds ratios = 1.2, 95% confidence interval = 1.1, 1.3, and 1.2, 95% confidence interval = 1.2, 1.3); no association was seen in children born to women exposed after the first trimester. CONCLUSION: Timing of folic acid-containing prescription filling during pregnancy was associated with childhood asthma. Our findings contribute to understanding of the role of prenatal nutritional supplements on child respiratory health.

Association of folic acid supplementation during pregnancy and infant bronchiolitis.

Viral bronchiolitis affects 20%-30% of infants; because there is no known effective treatment, it is important to identify risk factors that contribute to its pathogenesis. Although adequate folate intake during the periconceptional period prevents neural tube defects, animal data suggest that higher supplementation may be a risk factor for child respiratory diseases. Using a population-based retrospective cohort of 167,333 women and infants, born in 1995-2007 and enrolled in the Tennessee Medicaid program, we investigated the association between the filling of folic acid-containing prescriptions and infant bronchiolitis. We categorized women into the following 4 groups in relation to the first trimester: "none" (no prescription filled), "first trimester only," "after first trimester," and "both" (prescriptions filled both during and after the first trimester). Overall, 21% of infants had a bronchiolitis diagnosis, and 5% were hospitalized. Most women filled their first prescriptions after the fifth to sixth weeks of pregnancy, and most prescriptions contained 1,000 µg of folic acid. Compared with infants born to women in the "none" group, infants born to women in the "first trimester only" group had higher relative odds of bronchiolitis diagnosis (adjusted odds ratio = 1.17, 95% confidence interval: 1.11, 1.22) and greater severity (adjusted odds ratio = 1.16, 95% confidence interval: 1.11, 1.22). This study's findings contribute to an understanding of the implications of prenatal nutritional supplement recommendations for infant bronchiolitis.

PGI2 as a regulator of inflammatory diseases.

Prostacyclin, or PGI(2), is an end product derived from the sequential metabolism of arachidonic acid via cyclooxygenase and PGI synthase (PGIS). The receptor for PGI(2), IP, can be found on a variety of cell types and signaling through this receptor exhibits broad physiological effects. Historically, PGI(2) has been understood to play a role in cardiovascular health, specifically having powerful vasodilatory effects via relaxation of smooth muscle and inhibiting of platelet aggregation. For these reasons, PGI(2) has a long history of use for the treatment of pulmonary arterial hypertension (PAH). Only recently, its importance as an immunomodulatory agent has been investigated. PGI(2) regulates both the innate and adaptive immune systems and its effects are, for the most part, thought to be anti-inflammatory or immunosuppressive in nature, which may have implications for its further clinical use.

Food Allergy: Unproven diagnostics and therapeutics.

Food allergy or intolerance is often attributed by patients as the cause of many symptoms unknown to be directly related to food ingestion. For immunoglobulin E (IgE) mediated food allergy, diagnostic modalities are currently limited to the combination of clinical history, evidence of sensitization with food-specific IgE testing and skin-prick testing, and oral food challenge. Many patients find an appeal in the promise of identification of the etiology of their symptoms through alternative food allergy or intolerance diagnostic modalities. These patients may seek guidance from allergists or their general providers as to the legitimacy of these tests or interpretation of results. These tests include food-specific serum IgG or IgG4 testing, flow cytometry to measure the change in leukocyte volume after exposure to food, intradermal or sublingual provocation-neutralization, electrodermal testing, applied kinesiology, hair analysis, and iridology. In addition, there are some unconventional therapeutic modalities for adverse reactions to foods, including rotary diets. None of these have been supported by scientific evidence, and some even carry the risk of severe adverse reactions. It is important that we offer our patients evidence-based, accurate counseling of these unproven modalities by understanding their methods, their paucity of credible scientific support, and their associated risks.

Atopy history and the genomics of wheezing after influenza vaccination in children 6-59 months of age.

BACKGROUND: A multinational clinical trial compared the safety and efficacy of intranasal trivalent live attenuated influenza vaccine (LAIV) with intramuscular trivalent inactivated vaccine (TIV) in very young children prior to the 2004-5 influenza season [1]. Wheezing was noted more often in recipients of LAIV and laboratory-confirmed influenza infection was noted more often in recipients of TIV. We sought to determine whether epidemiologic or genetic factors were associated with these outcomes. METHODS: Atopy surveys and DNA collections were performed in trial participants at two United States sites, Nashville, TN and Boston, MA. DNA samples were genotyped on Illumina Infinium 610 or 660-Quad. Standard allelic tests of association were performed. RESULTS: At the Nashville and Boston sites, a total of 99 children completed the trial, 6 (1 TIV, 5 LAIV) developed medically attended wheezing within 42 days following vaccination, and 8 (5 TIV, 3 LAIV) developed laboratory-confirmed influenza during the season. Eighty-one surveys and 70 DNA samples were collected. Family history of asthma (p=0.001) was associated with wheezing after vaccination. Of 468,458 single nucleotide polymorphisms tested in the genome-wide association study (GWAS), none achieved genome-wide significance for either wheezing after vaccination or laboratory-confirmed influenza infection. CONCLUSIONS: Family history of asthma appears to be a risk factor for wheezing after influenza vaccination. Given the limitations of the sample size, our pilot study demonstrated the feasibility of performing a GWAS but was not able to determine genetic polymorphisms associated with wheezing after influenza immunization.

More pharmacists in high-risk neighborhoods of New York City support selling syringes to injection drug users.

OBJECTIVE: To document changes in pharmacists' opinions and practices from the time of passage to implementation of a law permitting selling syringes without a prescription (the Expanded Syringe Access Demonstration Program [ESAP]). DESIGN: Two cross-sectional randomized telephone surveys. SETTING: High-risk neighborhoods of New York City. SUBJECTS: Pharmacists. MAIN OUTCOME MEASURES: Support for selling syringes without a prescription to injection drug users (IDUs). RESULTS: We completed 130 surveys at baseline (BL) in August 2000, from neighborhoods with high numbers of injection-related acquired immunodeficiency syndrome (AIDS) cases and 231 surveys at law change (LC) in January 2001. To correct for differences in sampling, we limited the analysis to pharmacies in ZIP Codes represented in both samples and weighted results to adjust for the median income level of those postal codes. From BL (n = 83) to LC (n = 84), law awareness increased (43% to 90%, P < .001), as did personal support for selling syringes without a prescription to IDUs (36% to 63%, P < .001). From BL to LC, a larger proportion of supporters believed that selling syringes was an important part of human immunodeficiency virus (HIV) prevention and would help decrease HIV transmission, and a smaller proportion was concerned about customer discomfort and increased drug use. A total of 40% of respondents were ESAP registered at LC but registration was not associated with support for selling syringes to IDUs. CONCLUSIONS: Support for ESAP among pharmacists increased in high-risk neighborhoods as the program was implemented. The finding that some pharmacists were ESAP registered but did not support selling syringes to IDUs and others were supportive, but not ESAP registered, may have program implications.