Influence of the COVID-19 pandemic on the incidence and exacerbation of childhood allergic diseases.

To explore the influence of changes in human lifestyle and the living environment caused by nonpharmaceutical interventions in coronavirus disease 2019 (COVID-19) on allergic diseases, the present study enrolled children who came to the Children's Hospital of Zhejiang University for allergen detection between January 2019 and December 2020. By comparing the positive rates and levels of various allergen-specific immunoglobulin E (IgE) before and during the COVID-19 pandemic, the influence of changes in human lifestyle and the living environment caused by prevention and control measures in COVID-19 on allergic diseases was evaluated. In 2019, 41 648 allergic children went to the hospital, but in 2020, due to the impact of the COVID-19 epidemic, the number decreased to 24 714. In 2020, the number of allergy visits was the lowest in February and gradually increased. There were 45 879 children with total IgE > 17.5 IU/ml in 2 years, accounting for 69.13% of the total samples, of which the proportion was 68.52% (28 536/41 648) in 2019 and 70.17% (17 343/24 714) in 2020. A total of 29 906 children were positive for one or more allergens in 2 years. It accounts for 45.06% of the total number of samples, of which the proportion is 41.53% (17 296/41 648) in 2019 and 51.02% (12 610/24 714) in 2020. Except for cashew nuts, the positive number of other allergens in 2020 was less than in 2019, especially after June and July 2020. Except for Artemisia argyi, the positive rates of other allergens in 2020 were significantly higher than those in 2019 (p < 0.05). Moreover, the changing trend of the positive allergen rate in each month in 2020 was different from that in 2019. In 2020, except for Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Crab, specific IgE levels of other allergens were not greater than those in 2019 (p < 0.05). Thus it can be seen, during the COVID-19 pandemic, nonpharmaceutical interventions played a protective role in reducing children's exposure to allergens and alleviating allergic reactions.

Identification and biochemical characterization of Asp t 36, a new fungal allergen from Aspergillus terreus.

Aspergillus terreus is an allergenic fungus, in addition to causing infections in both humans and plants. However, the allergens in this fungus are still unknown, limiting the development of diagnostic and therapeutic strategies. We used a proteomic approach to search for allergens, identifying 16 allergens based on two-dimensional immunoblotting with A. terreus susceptible patient sera. We further characterized triose-phosphate isomerase (Asp t 36), one of the dominant IgE (IgE)-reactive proteins. The gene was cloned and expressed in Escherichia coli. Phylogenetic analysis showed Asp t 36 to be highly conserved with close similarity to the triose-phosphate isomerase protein sequence from Dermatophagoides farinae, an allergenic dust mite. We identified four immunodominant epitopes using synthetic peptides, and mapped them on a homology-based model of the tertiary structure of Asp t 36. Among these, two were found to create a continuous surface patch on the 3D structure, rendering it an IgE-binding hotspot. Biophysical analysis indicated that Asp t 36 shows similar secondary structure content and temperature sensitivity with other reported triose-phosphate isomerase allergens. In vivo studies using a murine model displayed that the recombinant Asp t 36 was able to stimulate airway inflammation, as demonstrated by an influx of eosinophils, goblet cell hyperplasia, elevated serum Igs, and induction of Th2 cytokines. Collectively, our results reveal the immunogenic property of Asp t 36, a major allergen from A. terreus, and define a new fungal allergen more broadly. This allergen could serve as a potent candidate for investigating component resolved diagnosis and immunotherapy.

Validation of Quantitative Structure-Activity Relationship (QSAR) and Quantitative Structure-Property Relationship (QSPR) approaches as alternatives to skin sensitization risk assessment.

The aim of this study was conducted to validate the physicochemical properties of a total of 362 chemicals [305 skin sensitizers (212 in the previous study + 93 additional new chemicals), 57 non-skin sensitizers (38 in the previous study + 19 additional new chemicals)] for skin sensitization risk assessment using quantitative structure-activity relationship (QSAR)/quantitative structure-property relationship (QSPR) approaches. The average melting point (MP), surface tension (ST), and density (DS) of the 305 skin sensitizers and 57 non-sensitizers were used to determine the cutoff values distinguishing positive and negative sensitization, and correlation coefficients were employed to derive effective 3-fold concentration (EC3 (%)) values. QSAR models were also utilized to assess skin sensitization. The sensitivity, specificity, and accuracy were 80, 15, and 70%, respectively, for the Toxtree QSAR model; 88, 46, and 81%, respectively, for Vega; and 56, 61, and 56%, respectively, for Danish EPA QSAR. Surprisingly, the sensitivity, specificity, and accuracy were 60, 80, and 64%, respectively, when MP, ST, and DS (MP+ST+DS) were used in this study. Further, MP+ST+DS exhibited a sensitivity of 77%, specificity 57%, and accuracy 73% when the derived EC3 values were classified into local lymph node assay (LLNA) skin sensitizer and non-sensitizer categories. Thus, MP, ST, and DS may prove useful in predicting EC3 values as not only an alternative approach to animal testing but also for skin sensitization risk assessment.

Applicability of the proposed GHS subcategorization criterion for LLNA:BrdU-ELISA (OECD TG442B) to the CBA/J strain mouse.

The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is a hazard classification and communication system for providing information on the safe handling of chemicals worldwide. In this study, we evaluated the applicability of the newly proposed GHS subcategorization criterion for murine local lymph node assay:2-bromodeoxyuridine enzyme-linked immunosorbent assay (LLNA:BrdU-ELISA), Category 1A:EC1.6 ≤6%, Category 1B:EC1.6 >6%, to data derived from LLNA:BrdU-ELISA performed in the CBA/J strain mouse. Fifteen chemicals categorized in GHS hazard Category 1 sensitizers listed in the LLNA performance standard were tested by LLNA:BrdU-ELISA in the CBA/J strain mouse and were classified according to the new criterion. The results revealed that all of the GHS 1A or 1B category chemicals classified according to the EC3 values derived from radioisotopic LLNA (LLNA-RI) could be correctly assigned into the respective 1A and 1B categories using the newly proposed GHS subclassification criterion. In addition, analysis of the correlation between the reported EC3 values and EC1.6 values derived from the LLNA:BrdU-ELISA performed in the CBA/J strain mouse confirmed the existence of a strong correlation (r = 0.9076, P < .0001). These findings suggest that the newly proposed GHS subcategorization criterion for LLNA:BrdU-ELISA is potentially applicable for practical use in GHS subcategorization.

Atopic Dermatitis: Identification and Management of Complicating Factors.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, associated with impaired skin barrier function and an atopic background. Various complicating factors, such as irritants, aeroallergens, food, microbial organisms, contact allergens, sweat, and scratching can induce the development of AD symptoms. Irritants, including soap/shampoo and clothes, can cause itching and eczematous lesions. In addition, young children with AD tend to become sensitized to eggs, milk, or peanuts, while older children and adults more often become sensitized to environmental allergens, such as house dust mites (HDM), animal dander, or pollen. Serum-specific IgE levels and skin prick test reactions to food tend to show high negative predictive values and low specificity and positive predictive values for diagnosing food allergy. On the other hand, AD adult patients tend to have severe skin symptoms and exhibit high HDM-specific IgE levels. Microbial organisms, e.g., Staphylococcus aureus and Malassezia furfur, might contribute to the pathogenetic mechanisms of AD. While sweat plays a major role in maintaining skin homeostasis, it can become an aggravating factor in patients with AD. Furthermore, scratching often exacerbates eczematous lesions. Several patient-specific complicating factors are seen in most cases. The identification and management of complicating factors are important for controlling AD.

Effect of pre-harvest and post-harvest conditions on the fruit allergenicity: A review.

Fruits are an important source of vitamins and antioxidants that can effectively delay aging and contribute to health and well-being of the human kind. However, they are growing to be one of the primary elicitors of food allergies around the world. Fruit allergens can induce an IgE-mediated (Immunoglobulin E) reaction, presenting with a symptom like localized oral allergy syndrome (OAS). Numerous studies showed that varying environmental and cultivation conditions can influence the fruit allergen content during flowering and ripening stages. Further, the variety, harvesting maturity, and storage conditions can also significantly influence the allergenicity potential. For example, unripe apples and tomatoes have lower levels of allergens compared to ripened fruits. Researchers have also reported that modified atmosphere packaging (MAP) can help reduce Mal d 3 content present in apples during storage. Post-harvest processing like peeling is also considered a good method to help reduce the overall allergenicity in few fruits whose peel might contain majority of the allergens. This review will discuss the overall influence of both pre-harvest and post-harvest factors on the fruit allergens. We will also discuss the progress regarding the cause, symptoms and diagnostic methods of fruit based allergies.

Pollen food allergy syndrome (PFAS): A review of current available literature.

OBJECTIVE: Pollen food allergy syndrome (PFAS) is a complex syndrome posing a diagnostic and therapeutic challenge. Our objective was to summarize the available literature regarding its prevalence, pathogenesis, diagnosis, and treatment. DATA SOURCES: A PubMed search was performed to include English language articles with the following search terms: pollen food syndrome, pollen food allergy syndrome, PFAS, oral allergy syndrome, OAS, food anaphylaxis, food components. STUDY SELECTIONS: Human articles discussing PFAS. RESULTS: Varying reports have been made of the prevalence of PFAS, ranging from 4.7% to greater than 20% in children and 13% to 58% in adults. Prevalence varies widely by geographic region. PFAS is typically the results of class II food allergens (e.g. sensitized to anaeroallergen, but reaction occurs due to cross reactivity from a food allergen). Commonly these reactions are limited to the oropharynx due to the lability of the proteins causing the reaction. As multiple families of proteins with varying stability cause PFAS, severe systemic reactions are also possible, as anaphylactic shock has been documented in up to 1.7% of reactions. CONCLUSION: Pollen food allergy syndrome therefore cannot be dismissed as a benign food allergy, but it needs to be approached individually based on known risk factors.

Proposal of GHS sub-categorization criteria for LLNA: BrdU-ELISA (OECD TG442B).

The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is a hazard classification and communication system for providing information on the safe handling of chemicals worldwide. While the GHS provides sub-categorization criteria for sensitizers when using the guinea pig maximization test/Buehler test (OECD TG406) and the standard radioisotopic LLNA (OECD TG429), the sub-categorization criteria for LLNA: BrdU-ELISA (OECD TG442B) are not currently provided. In this study, we re-analyzed the existing data of 32 sensitizers classified in the 1A or 1B categories of the GHS, and attempted to determine optimal criteria for GHS sub-categorization using LLNA: BrdU-ELISA. Consequently, the optimal criterion for the GHS sub-categorization was determined to be 6% when using EC1.6, showing the correct outcomes (%) for GHS 1A and GHS 1B category chemicals were 92.3 and 84.2 for all 32 chemicals, respectively. When excluding 2-mercaptobenzothiazole which may cause strain specific low response in this assay system, the correct outcomes (%) for GHS 1A chemicals was 100. Further work would be necessary, but the GHS sub-categorization criteria proposed in this study might be promising when using LLNA: BrdU-ELISA to provide information on the skin sensitization potency category of chemicals.

Chitinases as Food Allergens.

Food allergies originate from adverse immune reactions to some food components. Ingestion of food allergens can cause effects of varying severity, from mild itching to severe anaphylaxis reactions. Currently there are no clues to predict the allergenic potency of a molecule, nor are cures for food allergies available. Cutting-edge research on allergens is aimed at increasing information on their diffusion and understanding structure-allergenicity relationships. In this context, purified recombinant allergens are valuable tools for advances in the diagnostic and immunotherapeutic fields. Chitinases are a group of allergens often found in plant fruits, but also identified in edible insects. They are classified into different families and classes for which structural analyses and identification of epitopes have been only partially carried out. Moreover, also their presence in common allergen databases is not complete. In this review we provide a summary of the identified food allergenic chitinases, their main structural characteristics, and a clear division in the different classes.

Spectrum of Allergens and Allergen Biology in India.

The growing prevalence of allergy and asthma in India has become a major health concern with symptoms ranging from mild rhinitis to severe asthma and even life-threatening anaphylaxis. The "allergen repertoire" of this subcontinent is highly diverse due to the varied climate, flora, and food habits. The proper identification, purification, and molecular characterization of allergy-eliciting molecules are essential in order to facilitate an accurate diagnosis and to design immunotherapeutic vaccines. Although several reports on prevalent allergens are available, most of these studies were based on preliminary detection and identification of the allergens. Only a few of these allergen molecules have been characterized by recombinant technology and structural biology. The present review first describes the composition, distribution pattern, and natural sources of the predominant allergens in India along with the prevalence of sensitization to these allergens across the country. We go on to present a comprehensive report on the biochemical, immunological, and molecular information on the allergens reported so far from India. The review also covers the studies on allergy- related biosafety assessment of transgenic plants. Finally, we discuss the allergen-specific immunotherapy trials performed in India.

[Aeroallergens causing rhinoconjunctivitis]. / Principales aeroalérgenos en rinoconjuntivitis alérgica en la ciudad de Temuco, Chile.

BACKGROUND: Allergic rhinoconjunctivitis (ARC) has a prevalence of 30% in industrialized countries. For an accurate diagnosis and treatment, it is crucial to identify the causative aeroallergen. AIM: To evaluate aeroallergen sensitization in adults with ARC in the city of Temuco, Chile. PATIENTS AND METHODS: A skin test against the main aeroallergens present in Temuco was carried out in patients aged 15 to 64 years with ARC diagnosed by medical examination and the Score For Allergic Rhinitis. RESULTS: At least one aeroallergen sensitization was present in 234 (62.4%) out of 375 patients. Pollen-sensitized patients were positive mainly for Grasses (44.4%), Plantago (27.8%), Cynodon (26.1%), Sorrel (23.5%), Birch (14.9%), Nothofagus obliqua (13.3%) and Alder (11.1%). Dust mites were the most common non-pollinic sensitizing aeroallergens, including Dermatophagoides pteronyssinus (70.1%) and Dermatophagoides farinae (62.8%). CONCLUSIONS: According to our results, skin tests in the city of Temuco should include at least dust mites, pollens of Grasses, Plantago, Cynodon, Sorrel, Birch, Nothofagus obliqua and Alder, because these allergens account for 93% of ARC cases in this city.

IRRITANT AND ALLERGIC CONTACT DERMATITIS - SKIN LESION CHARACTERISTICS.

- Contact skin lesions may be the consequences of contact with various irritants or allergens, or due to other factors (e.g., UV radiation, microbials), intrinsic factors (e.g., in autoimmune responses), or even their combination. There are many substances related to irritant contact dermatitis (CD), causing irritant or toxic effects, e.g., chemical and physical agents, plants, phototoxic agents, airborne irritants, etc. Impaired barrier function (e.g., aberrancies in epidermal pH buffering capabilities) also participates by promoting bacterial biofilms and creating an environment favoring sensitization. Development of allergic CD skin lesions includes complex immune pathways and inflammatory mediators, influenced by both genetic (predominantly filaggrin mutations) and environmental triggers. In the pathogenesis of allergic CD, antimicrobial peptides play a prominent role; they are produced by various skin cells (e.g., keratinocytes, sebocytes) and move to inflamed lesions during an inflammation process. Also, in allergic CD skin lesions, the skin shows different types of immune responses to individual allergens, although clinical manifestations do not depend on the causative allergen type, e.g., nickel stimulates immune activation primarily of the Th1/Th17 and Th22 components. Also important are alarmins, proteases, immunoproteomes, lipids, natural moisturizing factors, tight junctions, smoking, etc. We expect that future perspectives may reveal new pathogenetic factors and scientific data important for the workup and treatment of patients with CD.

Origin and Functional Prediction of Pollen Allergens in Plants.

Pollen allergies have long been a major pandemic health problem for human. However, the evolutionary events and biological function of pollen allergens in plants remain largely unknown. Here, we report the genome-wide prediction of pollen allergens and their biological function in the dicotyledonous model plant Arabidopsis (Arabidopsis thaliana) and the monocotyledonous model plant rice (Oryza sativa). In total, 145 and 107 pollen allergens were predicted from rice and Arabidopsis, respectively. These pollen allergens are putatively involved in stress responses and metabolic processes such as cell wall metabolism during pollen development. Interestingly, these putative pollen allergen genes were derived from large gene families and became diversified during evolution. Sequence analysis across 25 plant species from green alga to angiosperms suggest that about 40% of putative pollen allergenic proteins existed in both lower and higher plants, while other allergens emerged during evolution. Although a high proportion of gene duplication has been observed among allergen-coding genes, our data show that these genes might have undergone purifying selection during evolution. We also observed that epitopes of an allergen might have a biological function, as revealed by comprehensive analysis of two known allergens, expansin and profilin. This implies a crucial role of conserved amino acid residues in both in planta biological function and allergenicity. Finally, a model explaining how pollen allergens were generated and maintained in plants is proposed. Prediction and systematic analysis of pollen allergens in model plants suggest that pollen allergens were evolved by gene duplication and then functional specification. This study provides insight into the phylogenetic and evolutionary scenario of pollen allergens that will be helpful to future characterization and epitope screening of pollen allergens.

Characteristics of tree nut challenges in tree nut allergic and tree nut sensitized individuals.

BACKGROUND: Characteristics and outcomes of tree nut (TN) oral food challenges (OFCs) in patients with TN allergy or sensitization alone are poorly studied. OBJECTIVE: To determine the relation between TN sensitization levels and OFC outcomes. METHODS: Open TN OFCs performed from 2007 through 2015 at a referral center were analyzed to compare outcome based on skin prick test (SPT) wheal size, food-specific immunoglobulin E (sIgE), peanut co-allergy, and TN sensitization only vs TN allergy with sensitization to other TNs. Delayed OFC was defined as longer than 12 months from the time of an sIgE level lower than 2 kUA/L. RESULTS: Overall passage rate was 86% for 156 TN OFCs in 109 patients (54 almond, 28 cashew, 27 walnut, 18 hazelnut, 14 pecan, 13 pistachio, and 2 Brazil nut). Passage rates were 76% (n = 67) in patients with a history of TN allergy who were challenged to another TN to which they were sensitized and 91% (n = 65) in those with TN sensitization only (mean sIgE 1.53 kUA/L; range 0.35-9.14). Passage rates were 89% (n = 110 of 124) for a TN sIgE level lower than 2 kUA/L and 69% (11 of 16) for a TN sIgE level of at least 2 kUA/L. In 44 challenges in patients with peanut allergy and TN co-sensitization, the TN OFC passage rate was 96%. In 41 TN OFCs with a TN SPT wheal size of at least 3 mm, 61% passed, with a mean wheal size of 4.8 mm (range 3-11) in those passing vs 9 mm (range 3-20) in those failing. CONCLUSION: TN challenges are frequently passed in patients with TN sensitization with or without a history of TN reactivity despite a TN SPT wheal of at least 3 mm or a TN sIgE level of at least 2 kUA/L. Nearly all patients with peanut allergy and TN co-sensitization passed the TN challenge, questioning the clinical relevance of "co-allergy."

Epidemiology of anaphylaxis at a tertiary care center: A report of 730 cases.

BACKGROUND: Recent data reveal that the rate of anaphylaxis is increasing and suggest that idiopathic anaphylaxis may account for most of these cases. OBJECTIVE: To determine the pattern of anaphylaxis at a tertiary care referral center. METHODS: A retrospective electronic medical record review spanning 12 years (2002-2013) identified patients with anaphylaxis. RESULTS: Of the 4,777 records reviewed, 730 patients met our anaphylaxis definition. Median age was 34.0 years; 72.7% were adults, 58.6% were female, and 86.8% were white. Median time to evaluation by an allergist was 8.8 months. Foods were the most common cause (29.9%), followed by Hymenoptera venom (24.6%), idiopathic anaphylaxis (13.7%), and medications (13.3%). The most common foods were peanuts (23.9%), tree nuts (21.6%), shellfish (16.1%), and egg and milk (both 10.1%). The most common cause of anaphylaxis in adults was Hymenoptera venom. The most frequent symptoms were urticaria and/or angioedema, reported in 84.7% of cases. Atopy was present in 43.8%. In 15.4% of cases, anaphylaxis was not the chief reason for the office visit. CONCLUSION: We found food allergy was the most common overall cause of anaphylaxis, with peanut the most frequent food trigger. Idiopathic anaphylaxis was not the most common cause but accounted for 13.7% of all cases. Approximately 1 in 6 cases of anaphylaxis may be missed if a comprehensive evaluation is not performed.

Prevalence of food allergies in South Asia.

OBJECTIVE: To evaluate the published medical literature on the prevalence and types of food allergies in South Asia. DATA SOURCES: A PubMed search was performed using the keywords India and food allergy, Asia and food allergy, and South Asia and food allergy for any period. Articles cited in selected studies were reviewed for their appropriateness of inclusion into this review. STUDY SELECTIONS: Publications were included that were original research and fit the topic of food allergy and South Asia. South Asia is defined as region inclusive of India, Pakistan, Bangladesh, and Sri Lanka. RESULTS: A total of 169 articles were initially identified, and 47 were reviewed in detail for inclusion in this review. The primary focus was placed on 10 studies that consisted of case reports of newly reported or documented food allergy, survey studies that investigated food allergy prevalence in specific demographics, and prospective and cross-sectional studies with case controls, all of which investigated food allergy prevalence by allergy testing in a selected population. CONCLUSION: The medical literature on the prevalence and types of food allergy in South Asia indicates that there is a variety of unusual and unique allergens and an overall low incidence of food allergy. There is also an association of increased food allergy prevalence in individuals who live in metropolitan regions or who migrate to communities that have adopted westernization.

Mammalian raw materials used to produce allergen extracts.

OBJECTIVE: To provide information about the complexity of skin-derived mammalian allergen extracts and recent advances made in their characterization and production. DATA SOURCES: Original and review articles (involving nonfood allergy to mammals) published in indexed journals were searched in the PubMed database. STUDY SELECTIONS: Studies were selected with the following criteria: novelty, species of the study, and date of publication. RESULTS: The information provided will help in the understanding and the selection of the appropriate allergen source materials for the preparation of extracts for the diagnosis and treatment of allergic respiratory diseases induced by the inhalation of skin-derived mammalian allergens. The data presented herein suggest the presence of cross-reactive and species-specific allergens in extracts prepared from different mammalian dander. Dander should be strongly considered in the preparation of allergenic extracts not only of cats and dogs but also of other mammalian species. CONCLUSION: New methods should be developed to estimate the relative quantities of specific allergens in the extracts. The current knowledge illustrates the complexity of these extracts, and more efforts should be undertaken to fully understand the wide spectrum of mammalian allergens.

Association of atopy phenotypes with new development of asthma and bronchial hyperresponsiveness in school-aged children.

BACKGROUND: Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood. OBJECTIVE: To identify atopy phenotypes in school-age children and to evaluate the association between atopy phenotypes and allergic diseases. METHODS: We enrolled 616 children with atopy defined as 1 or more positive allergen responses on skin prick tests and 665 children without atopy from the Children's Health and Environmental Research (CHEER) study. All children were followed up for 4 years at 2-year intervals. Atopy phenotypes were classified using latent class analysis. RESULTS: Four atopy phenotypes were characterized: later sensitization to indoor allergens (cluster 1); multiple early sensitization (cluster 2); early sensitization to outdoor allergens, especially Alternaria, and later sensitization to indoor allergens, including Aspergillus (cluster 3); and early sensitization to indoor allergens and later sensitization to outdoor allergens (cluster 4). New cases of asthma during follow-up were increased in clusters 2 and 3 (adjusted odds ratio [aOR], 2.76 and 4.25, respectively). The risk of new-onset bronchial hyperresponsiveness was highest in cluster 3 (aOR, 5.03). Clusters 2 and 4 had an increased risk of allergic rhinitis (aOR, 7.21 and 2.37, respectively). CONCLUSION: Identification of atopy phenotypes facilitates prediction of the development of asthma and bronchial hyperresponsiveness in school-age children. Our study suggests prevention of additional sensitization is required to modify the progression of allergic diseases.

Factors associated with poor controller medication use in children with high asthma emergency department use.

BACKGROUND: Understanding health and social factors associated with controller medication use in children with high-risk asthma may inform disease management in the home and community. OBJECTIVE: To examine health and social factors associated with the Asthma Medication Ratio (AMR), a measure of guideline-based care and controller medication use, in children with persistent asthma and frequent emergency department (ED) use. METHODS: Study questionnaires, serum allergen sensitization, salivary cotinine, and pharmacy record data were collected for 222 children enrolled from August 2013 to February 2016 in a randomized clinical trial that tested the efficacy of an ED- and home-based intervention. Logistic regression was used to examine factors associated with an AMR greater than 0.50, reflecting appropriate controller medication use. RESULTS: Most children were male (64%), African American (93%), Medicaid insured (93%), and classified as having uncontrolled asthma (44%). Almost half (48%) received non-guideline-based care or low controller medication use based on an AMR less than 0.50. The final regression model predicting an AMR greater than 0.50 indicated that children receiving specialty care (odds ratio [OR], 4.87; 95% confidence interval [CI], 2.06-11.50), caregivers reporting minimal worry about medication adverse effects (OR, 0.50; 95% CI, 0.25-1.00), positive sensitization to ragweed allergen (OR, 3.82; 95% CI, 1.63-8.96), and negative specific IgE for dust mite (OR, 0.33; 95% CI, 0.15-0.76) were significantly associated with achieving an AMR greater than 0.50. CONCLUSION: Clinical decision making for high-risk children with asthma may be enhanced by identification of sensitization to environmental allergens, ascertaining caregiver's concerns about controller medication adverse effects and increased referral to specialty care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01981564.

Evaluation of radioisotopic and non-radioisotopic versions of local lymph node assays for subcategorization of skin sensitizers compliant to UN GHS rev 4.

Recently UN GHS has introduced the sub-categorization of skin sensitizers for which ECt (concentration estimated to induce stimulation index above threshold) of the murine local lymph node assay (LLNA) is used as criteria. Non-radioisotopic variants of LLNA, LLNA: DA, LLNA: BrdU-ELISA, LNCC and LLNA: BrdU-FCM were developed yet their utilities for potency sub-categorization are not established. Here we assessed the agreement of LLNA variants with LLNA or human data in potency sub-categorization for 22 reference substances of OECD TG429. Concordance of sub-categorization with LLNA was highest for LLNA: BrdU-FCM(91%, κ = 0.833, weighted kappa) followed by LLNA: BrdU-ELISA (82%, κ = 0.744) and LLNA: DA (73%, κ = 0.656) whereas LNCC only showed a modest association (64%, κ = 0.441). With human data, LLNA agreed best (77%) followed by LLNA: DA and LLNA: BrdU-FCM(73%), LLNA: BrdU-ELISA (68%) and LNCC(55%). Bland-Altman plot revealed that ECt's of LLNA variants largely agreed with LLNA where most values fell within 95% limit of agreement. Correlation between ECt's of LLNA and LLNA variants were high except for LNCC(pair-wise with LLNA, LLNA: DA, r = 0.848, LLNA: BrdU-ELISA, r = 0.744, LLNA: BrdU-FCM, r=0.786, and LNCC, r = 0.561 by Pearson). Collectively, these results demonstrated that LLNA variants exhibit performance comparable to LLNA in the potency sub-categorization although additional substances shall be analyzed in the future.