Person:

Phipatanakul, Wanda

Background: Ovomucoid is the dominant allergen in hen's egg. Although several studies evaluated the utility of ovomucoid specific immunoglobulin E (sIgE) levels in predicting baked (e.g., muffin or cupcake) or raw egg food challenge outcomes, studies that evaluated ovomucoid sIgE as a predictor of cooked egg (e.g., scrambled or hard boiled) challenge outcomes are limited. Objective: To determine the relation of ovomucoid sIgE levels with cooked egg food challenge outcomes. Methods: A retrospective review of 44 children who underwent cooked egg food challenge and who had the ovomucoid sIgE level measured. Results: Thirty-six of 44 children (81.8%) passed cooked egg challenge. The ovomucoid sIgE level predicted cooked egg challenge outcome (passed median, <0.35 kU/L [range, <0.35–0.64 kU/L]; failed median, 0.40 kU/L [range, <0.35–3.13 kU/L]; p = 0.004). Ovomucoid sIgE levels correlated with egg white (EW) sIgE levels (Spearman correlation coefficient, 0.588; p < 0.001). Receiver operating characteristic curve analysis of ovomucoid and EW sIgE demonstrated areas under the curve of 0.711 and 0.766, respectively. No significant difference was observed among those immunologic parameters in their abilities to predict cooked egg challenge outcome (p = 0.559). Conclusion: The ovomucoid sIgE level may be helpful in predicting cooked egg challenge outcomes. However, our study did not support a role for ovomucoid sIgE replacing EW sIgE testing in evaluating egg allergy.

Allergic rhinitis is a common comorbid condition in pediatric chronic rhinosinusitis (CRS). Testing for aeroallergen sensitization should therefore be considered in the evaluation of children with CRS. At present the aeroallergen sensitivity profile of children with CRS remains uncharacterized. In this study, we retrospectively identify a consecutive series of children with CRS and allergic rhinitis who have undergone joint otolaryngology and allergy evaluation at a single tertiary care center. We describe the aeroallergen sensitivity profiles (based upon formal skin testing) of these children, stratifying them according to co-morbidity status: 1) CRS with cystic fibrosis (CF), 2) CRS with immune deficiency and 3) uncomplicated CRS (without co-morbid CF, immune deficiency or primary ciliary dyskinesia). We identify 208 children (average age 9.3 years, standard deviation 4.8 years) with CRS and allergic rhinitis meeting inclusion criteria, 140 with uncomplicated CRS, 64 with co-morbid immune deficiency and 4 with co-morbid CF. The prevalence of indoor aeroallergen sensitivities (62.9–100.0%) was more common than that of outdoor aeroallergen sensitivities (43.8–50.0%) in all three cohorts of children. In all three cohorts, the most common indoor aeroallergen sensitivity was to dust mites (50.0–75.0%) and the most common outdoor aeroallergen sensitivity was to tree pollens (43.8–50.0%). The aeroallergen sensitivity profile of children with CRS and allergic rhinitis appears to be similar to that of the general pediatric population with allergic rhinitis, and parallels the aeroallergen sensitivities previously described for adults with CRS and allergic rhinitis. Knowledge of the aeroallergen sensitivities in children with CRS and allergic rhinitis will enhance both diagnostic and treatment strategies.

Background: Previous research has found relationships between specific indoor environmental exposures and exacerbation of asthma. Objectives: In this review we provide an updated summary of knowledge from the scientific literature on indoor exposures and exacerbation of asthma. Methods: Peer-reviewed articles published from 2000 to 2013 on indoor exposures and exacerbation of asthma were identified through PubMed, from reference lists, and from authors’ files. Articles that focused on modifiable indoor exposures in relation to frequency or severity of exacerbation of asthma were selected for review. Research findings were reviewed and summarized with consideration of the strength of the evidence. Results: Sixty-nine eligible articles were included. Major changed conclusions include a causal relationship with exacerbation for indoor dampness or dampness-related agents (in children); associations with exacerbation for dampness or dampness-related agents (in adults), endotoxin, and environmental tobacco smoke (in preschool children); and limited or suggestive evidence for association with exacerbation for indoor culturable Penicillium or total fungi, nitrogen dioxide, rodents (nonoccupational), feather/down pillows (protective relative to synthetic bedding), and (regardless of specific sensitization) dust mite, cockroach, dog, and dampness-related agents. Discussion: This review, incorporating evidence reported since 2000, increases the strength of evidence linking many indoor factors to the exacerbation of asthma. Conclusions should be considered provisional until all available evidence is examined more thoroughly. Conclusion: Multiple indoor exposures, especially dampness-related agents, merit increased attention to prevent exacerbation of asthma, possibly even in nonsensitized individuals. Additional research to establish causality and evaluate interventions is needed for these and other indoor exposures. Citation: Kanchongkittiphon W, Mendell MJ, Gaffin JM, Wang G, Phipatanakul W. 2015. Indoor environmental exposures and exacerbation of asthma: an update to the 2000 review by the Institute of Medicine. Environ Health Perspect 123:6–20; http://dx.doi.org/10.1289/ehp.1307922

Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the current knowledge on mite allergens, routes of sensitization, the genetics of IgE responses to mites, the epidemiologic aspects of mite hypersensitivity, the clinical pictures induced by mites, the diagnosis, specific immunotherapeutic approaches, and prevention.

This paper continues an initiative conducted by the International Society for Disease Surveillance with funding from the Defense Threat Reduction Agency to connect near-term analytical needs of public health practice with technical expertise from the global research community. The goal is to enhance investigation capabilities of day-to-day population health monitors. A prior paper described the formation of consultancies for requirements analysis and dialogue regarding costs and benefits of sustainable analytic tools. Each funded consultancy targets a use case of near-term concern to practitioners. The consultancy featured here focused on improving predictions of asthma exacerbation risk in demographic and geographic subdivisions of the city of Boston, Massachusetts, USA based on the combination of known risk factors for which evidence is routinely available. A cross-disciplinary group of 28 stakeholders attended the consultancy on March 30-31, 2016 at the Boston Public Health Commission. Known asthma exacerbation risk factors are upper respiratory virus transmission, particularly in school-age children, harsh or extreme weather conditions, and poor air quality. Meteorological subject matter experts described availability and usage of data sources representing these risk factors. Modelers presented multiple analytic approaches including mechanistic models, machine learning approaches, simulation techniques, and hybrids. Health department staff and local partners discussed surveillance operations, constraints, and operational system requirements. Attendees valued the direct exchange of information among public health practitioners, system designers, and modelers. Discussion finalized design of an 8-year de-identified dataset of Boston ED patient records for modeling partners who sign a standard data use agreement.

Mechanisms by which regulatory T (Treg) cells fail to control inflammation in asthma remain poorly understood. We show that a severe asthma-associated polymorphism in the interleukin-4 receptor alpha chain (IL4RA R576) promotes conversion of induced Treg (iTreg) cells towards a T helper 17 (TH17) cell fate. This skewing is mediated by the recruitment by IL-4Rα-R576 of the growth factor receptor-bound protein 2 (GRB2) adaptor protein, which drives IL-17 expression by activating a pathway involving extracellular signal-regulated kinase, IL-6 and STAT3. Treg cell-specific deletion of Il6ra or Rorc, but not Il4 or Il13, prevented exacerbated airway inflammation in Il4raR576 mice. Furthermore, treatment of Il4raR576 mice with a neutralizing anti-IL-6 antibody prevented iTreg cell reprogramming into TH17-like cells and protected against severe airway inflammation. These findings identify a novel mechanism for the development of mixed TH2-TH17 cell inflammation in genetically prone individuals, and point to interventions that stabilize iTreg cells as potentially effective therapeutic strategies.

Clinicians who care for children with asthma have an obligation to coordinate asthma care with the schools. Aside from routine clinical care of asthmatic children, providers must educate the family and child about the need for an asthma treatment plan in school and support the school nurse meeting the needs of the student requiring school-based asthma care. The following article was developed by multiple stakeholders to address this need. It describes the 4 components of the School-based Asthma Management Program (SAMPRO™). SAMPRO™ details elements necessary for the education of children, families, clinicians, and school-based personnel based on a “circle of support” that would enhance multidirectional communication and promote better care for children with asthma within the school setting.

Background: Although pre-puberty asthma is more prevalent in males, after puberty through middle-age, asthma is more prevalent in females. The surge of sex hormones with puberty might explain this gender switch. Methods: To examine the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6–18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program (SARP). The effects of circulating sex hormones (n = 68; testosterone, dehydroepiandrosterone sulfate (DHEA-S), estrogen, and progesterone) on lung function and 4 week symptom control (ACQ6) in cross-section were tested by linear regression. Results: From pre−/early to late puberty, lung function did not change significantly but ACQ6 scores improved in males with severe asthma. By contrast females had lower post-BD FEV1% and FVC% and worse ACQ6 scores with late puberty assessed by breast development. In males log DHEA-S levels, which increased by Tanner stage, associated positively with pre- and post-BD FEV1%, pre-BD FVC %, and negatively (improved) with ACQ6. Patients treated with high-dose inhaled corticosteroids had similar levels of circulating DHEA-S. In females, estradiol levels increased by Tanner stage, and associated negatively with pre-BD FEV1% and FVC %. Conclusions: These results support beneficial effects of androgens on lung function and symptom control and weak deleterious effects of estradiol on lung function in children with asthma. Longitudinal data are necessary to confirm these cross-sectional findings and to further elucidate hormonal mechanisms informing sex differences in asthma features with puberty. Trial registration ClinicalTrials.gov registration number: NCT01748175. Electronic supplementary material The online version of this article (10.1186/s12890-018-0612-x) contains supplementary material, which is available to authorized users.

BACKGROUND Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking.

METHODS In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both treatment groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial.

RESULTS Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P = 0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P = 0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P = 0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P = 0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P = 0.94), or adverse events.

CONCLUSIONS Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen.