Allergic Group Research Articles

Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status.

BackgroundThe pandemic of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID‐19 children with different severities and allergic status.MethodsData extracted from the electronic medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results, and radiological images of 182 hospitalized COVID‐19 children, were summarized and analyzed.ResultsThe median age was 6 years, ranging from 3 days to 15 years, and there were more boys (male‐female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort, and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground‐glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia (manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase, and serum interleukins (IL)‐2, IL‐4, IL‐6, IL‐10, and TNF‐α. There were no differences in treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing, and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID‐19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID‐19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy, and asthma. Demographics and clinical features were not significantly different between allergic and nonallergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D‐dimer, and aspartate aminotransferase levels compared with all patients. Immunological profiles including circulating T, B, and NK lymphocyte subsets, total immunoglobulin and complement levels, and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subset numbers, and serum cytokine levels.ConclusionPediatric COVID‐19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and nonallergic COVID‐19 children in disease incidence, clinical features, and laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS‐CoV‐2 infection and hardly influenced the disease course of COVID‐19 in children.

<em>Helicobacter pylori</em> is associated with weakened pulmonary function and reduced incidence of allergic conditions in patients with chronic cough

The present study aimed to investigate the potential association between Helicobacter pylori (a H. pylori) positive state and chronic cough. A clinical observational study with systematic analysis was performed, including 278 patients with complaints of chronic cough and 148 healthy controls. a H. pylori positive state was present in 61.2% of the patients in the chronic cough group and 68.9% in the chronic refractory cough group, as opposed to 43.9% in the control group. There was a significant improvement in 65.5% of the patients with chronic refractory cough following successful a H. pylori eradication therapy. In addition, patients with chronic cough exposed to a H. pylori exhibited decreased pulmonary function with a decrease in forced expiratory volume in 1 sec by 84 ml, a decrease in the forced vital capacity by 53 ml and a decrease in maximal vital capacity by 46 ml. The difference was even more obvious in the chronic refractory cough group. The allergy status differed significantly according to age between a H. pylori-positive and -negative cases in the cough variant asthma and allergic cough groups. Among patients aged <40 years, a H. pylori-positive cases had a lower prevalence of atopy and lower total serum immunoglobin E levels compared with a H. pylori-negative cases. However, there was no significant association between a H. pylori status and C-reactive protein levels, erythrocyte sedimentation rate or eosinophil count in the peripheral blood. In conclusion, the present study demonstrated that a H. pylori infection may be a factor associated with chronic cough and it may be associated with a decline in pulmonary function and reduced incidence of allergic conditions. Thus, a H. pylori may represent a target for the treatment of chronic cough.

Common food allergens and cross-reactivity.

The most clinically relevant food allergens are cow's milk, hen's egg, peanut, tree nuts, wheat, soy, fish, shellfish, and seeds. Heat-stable food allergens have molecular characteristics that enhance protein stability and gastrointestinal absorption and thus are more likely to cause systemic reactions on ingestion. In contrast, heat-labile food allergens lack these characteristics and do not typically elicit reactions if sufficiently altered by heat or acid. Immunologic cross-sensitization between food allergens is more common than clinical cross-reactivity. However, certain groups of food allergens, such as tree nuts, fish, and shellfish, are associated with high rates of clinical cross-reactivity. Knowing the rates of clinical cross-reactivity is important when providing guidance to patients with food allergy and families on what foods can be safely added to the diet and what foods should be avoided.

Retinoic Acid Ameliorates the Severity of Food Allergy under Allergen Exposure in a Mouse Model with Food Allergy.

Effectiveness of retinoic acid (RA) in treating food allergy is not yet clear. Using an allergic mouse model, we examined the amelioration of the severity of food allergy by daily RA intake with allergen or without. Female Balb/c mice were systemically sensitized to egg white (EW) and alum by intraperitoneal injection. Sensitized mice were provided diets supplemented with 0% (non-treated group), 0.1% EW (allergen group), 0.0017% RA (RA group), or 0.1% EW plus 0.0017% RA (RA+allergen group) with 20% casein for 4 wk. Oral food challenge (OFC) and allergic biomarkers were quantified. The decrease in rectal temperature post-OFC was significantly suppressed in the RA and RA+allergen groups compared to those in the non-treated and allergen groups, respectivety. The plasma levels of ovalbumin-specific IgE, IgA and IgG1 at the study endpoint were higher in the allergen and RA+allergen groups than those in the non-treated and RA+allergen groups, respectivety. Plasma ovalbumin-specific IgG2a levels at the study endpoint were significantly higher in the RA+allergen group than those in the RA groups. The supernatant concentrations of interleukin-10 and interferon-γ in the cultured spleen lymphocytes were highest in the RA+allergen group compared to those in the other groups. Thus, continuous intake of RA under allergen exposure ameliorated the severity of food allergy in a mouse model with food allergy.

Cognitive dysfunction and quality of life during pollen season in children with seasonal allergic rhinitis.

BackgroundAllergic rhinitis often gives rise to impaired quality of life and is believed to also affect cognitive function. We aimed to examine whether cognitive functions were impaired during grass pollen season in symptomatic allergic children and to relate the degree of impairment to quality of life and biomarkers related to stress and inflammation.MethodsForty‐three grass pollen‐allergic children (age 8‐17 years) with non‐satisfactory effect of medication (antihistamines and nasal steroids daily) during previous seasons were included. In addition, 26 matched non‐allergic children were included as controls. Both groups performed cognitive tests (CANTAB) and completed Quality of Life questionnaires outside and during the pollen season. Blood samples were collected and analyzed for stress and inflammatory biomarkers. Pollen level was measured daily.ResultsImpaired cognitive function was found in spatial working memory, where the allergic group made more errors compared to the non‐allergic group during pollen season, but not off‐season. No significant differences could be seen between the allergic group and the controls in the other tests investigating visual memory or attention. Quality of health questionnaires revealed more symptoms and impaired quality of life in allergic compared to non‐allergic children, and increased symptoms in allergic children were associated with longer reaction time for simple movement during pollen season. No differences in stress or inflammatory biomarkers could be found between the groups.ConclusionCognitive function was affected during pollen season in pollen‐allergic children, and the more symptoms the allergic children had, the longer the reaction time in the cognitive tests.

Inflammatory characterization of different non-allergic rhinitis in patients attending tertiary care hospital

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Non-allergic rhinitis is a chronic inflammation of nasal cavity, which can be classified based on the level of eosinophil. Thus, the present study aimed to characterize the various types of non-allergic rhinitis.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This study conducted during the period of 1 year from April 2019 to February 2020 in the ENT department of MNR Medical College and Hospital, Sangareddy. A total of 60 participants were enrolled in this study. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; In case of non-allergic rhinitis, the nasal IL-17 level was 27.31±5.1, IL-4 level was 44.24±21.31, as well as serum IL-4 and IL-17 level was 50.1 and 31.06 respectively. The control group IL-4 and IL-17 level were respectively less (p&amp;lt;0.05). But the IL-10 level (3.7) and proportion of tregs in peripheral blood (5.2) were lower than the control group (p&amp;lt;0.05). There was no significant difference found between the non-allergic rhinitis group and allergic rhinitis group or the non-allergic rhinitis without eosinophilia group and the control group (p&amp;gt;0.05).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Hence, the non-allergic rhinitis was classified on the basis of eosinophil level, allergic rhinitis and NARES had similar kind of inflammatory response, but two different types of non-allergic rhinitis had different inflammatory characteristics. Therefore, it is recommended to classify the rhinitis on the basis of eosinophil level.&lt;/p&gt;

The Atopy Index Inventory: A Brief and Simple Tool to Identify Atopic Patients

Introduction: Atopy and ear, nose and throat (ENT) diseases are frequently associated; however, no clinical tool has been proposed so far to discriminate which patients could be atopic and therefore deserving of a further immunoallergological evaluation. Objective: The aim of this study was to assess and validate a set of dichotomous responses suitable for predicting the presence of atopy in adult patients. Methods: An 11-item questionnaire, i.e., the Atopy Index Inventory (AII), comprised of 4 questions regarding the clinical history for allergic disease and 7 questions evaluating the presence of the most frequent clinical signs affecting allergic patients, was developed and administered to 226 adult subjects (124 atopic subjects and 102 healthy, not atopic subjects). The atopic condition was proven by an immunoallergological evaluation according to the diagnostic criteria of the EAACI guidelines. Internal consistency and clinical validity were tested. Results: In healthy subjects, the first 4 variables of the AII returned a 100% correct response (all answered “no”) and were defined as “decisive” responses. In the logistic regression analysis, when decisive items were negative, the atopic condition was confirmed when answering “yes” to at least 3 “probability” items (cut-off = 2.69). The difference in AII scores between allergic and healthy group was significant using the Mann-Whitney U test (p < 0.0001). The sensitivity and specificity of the AII were 0.97 and 0.91, respectively, with a true predictive value of 0.92 and a false predictive value of 0.97. The ROC curve showed an area of 0.94, with an OR of 0.88 (95% CI 0.87–0.97, p = 0.0001). The internal consistency as determined by the Cronbach α coefficient was 0.88. Conclusion: The AII has been proven to be a brief, simple and sufficiently accurate tool for screening ENT patients in search of atopic individuals and to allow their clinical management.

Early epitope-specific IgE antibodies are predictive of childhood peanut allergy

Peanut allergy is characterized by the development of IgE against peanut antigen. We sought to evaluate the evolution of epitope-specific (es)IgE and esIgG4 in a prospective cohort of high-risk infants to determine whether antibody profiles can predict peanut allergy after age 4 years. The end point was allergy status at age 4+ years; samples from 293 children were collected at age 3 to 15 months and 2 to 3 and 4+ years. Levels of specific (s)IgE and sIgG4 to peanut and component proteins, and 50 esIgE and esIgG4 were quantified. Changes were analyzed with mixed-effects models. Machine learning algorithms were developed to identify a combination of antigen- and epitope-specific antibodies that using 3- to 15-month or 2- to 3-year samples can predict allergy status at age 4+ years. At age 4+ years, 38% of children were Tolerant or 14% had Possible, 8% Convincing, 24% Serologic, and 16% Confirmed allergy. At age 3 to 15 months, esIgE profiles were similar among groups, whereas marked increases were evident at age 2 and 4+ years only in Confirmed and Serologic groups. In contrast, peanut sIgE level was significantly lower in the Tolerant group at age 3 to 15 months, increased in Confirmed and Serologic groups but decreased in Convincing and Possibly Allergic groups over time. An algorithm combining esIgEs with peanut sIgE outperformed different clinically relevant IgE cutoffs, predicting allergy status on an "unseen" set of patients with area under the curves of 0.84 at age 3 to 15 months and 0.87 at age 2 to 3 years. Early epitope-specific plus peanut-specific IgE is predictive of allergy status at age 4+ years.

Allergome-wide peptide microarrays enable epitope deconvolution in allergen-specific immunotherapy

The interaction of allergens and allergen-specific IgE initiates the allergic cascade after crosslinking of receptors on effector cells. Antibodies of other isotypes may modulate such a reaction. Receptor crosslinking requires binding of antibodies to multiple epitopes on the allergen. Limited information is available on the complexity of the epitope structure of most allergens. We sought to allow description of the complexity of IgE, IgG4, and IgG epitope recognition at a global, allergome-wide level during allergen-specific immunotherapy (AIT). We generated an allergome-wide microarray comprising 731 allergens in the form of more than 172,000 overlapping 16-mer peptides. Allergen recognition by IgE, IgG4, and IgG was examined in serum samples collected from subjects undergoing AIT against pollen allergy. Extensive induction of linear peptide-specific Phl p 1- and Bet v 1-specific humoral immunity was demonstrated in subjects undergoing a 3-year-long AIT against grass and birch pollen allergy, respectively. Epitope profiles differed between subjects but were largely established already after 1 year of AIT, suggesting that dominant allergen-specific antibody clones remained as important contributors to humoral immunity following their initial establishment during the early phase of AIT. Complex, subject-specific patterns of allergen isoform and group cross-reactivities in the repertoires were observed, patterns that may indicate different levels of protection against different allergen sources. The study highlights the complexity and subject-specific nature of allergen epitopes recognized following AIT. We envisage that epitope deconvolution will be an important aspect of future efforts to describe and analyze the outcomes of AIT in a personalized manner.

Sojadodamgangki-tang attenuates allergic lung inflammation by inhibiting T helper 2 cells and Augmenting alveolar macrophages

Ethnopharmacological relevanceSojadodamgangki-tang (SDG) is a traditional East-Asian herbal medicine mainly composed of Pinellia ternate (Thunb.) Makino, Perilla frutescens (L.) Britt and 10 kinds of medicinal herbs. It has been used to treat asthma and mucus secretion including lung and bronchi. Aim of the studyThe aim of this study was to investigate the anti-inflammatory effects of Sojadodamgangki-tang (SDG) on allergic lung inflammation in vitro and in vivo as well as the underlying mechanisms. Materials and methodsWe used an ovalbumin (OVA)-induced murine allergic airway inflammation model. Five groups of 8-week-old female BALB/C mice were divided into the following groups: saline control group, the vehicle (allergic) group that received OVA only, groups that received OVA and SDG (200 mg/kg or 400 mg/kg), and a positive control group that received OVA and Dexamethasone (5 mg/kg). In vitro experiments include T helper 2 (TH2) polarization system, murine macrophage cell culture, and human bronchial epithelial cell line (BEAS-2B) culture. ResultsSDG administration reduced allergic airway inflammatory cell infiltration, especially of eosinophils, mucus production, Th2 cell activation, OVA-specific immunoglobulin E (IgE), and total IgE production. Moreover, the activation of alveolar macrophages, which leads to immune tolerance in the steady state, was promoted by SDG treatment. Interestingly, SDG treatment also reduced the production of alarmin cytokines by the human bronchial epithelial cell line BEAS-2B stimulated with urban particulate matter. ConclusionOur findings indicate that SDG has potential as a therapeutic drug to inhibit Th2 cell activation and promote alveolar macrophage activation.

Study on expression and mechanism of serum differential proteins after rush immunotherapy of allergic rhinitis

Objective:To detect the expression of differentially expressed proteins in serum of patients with allergic rhinitis who were allergic to dust mites before and after 6-day rush immunotherapy. The three differentially expressed proteins, CRP, CTHRC1 and WDR89, were detected and identified. The immunoregulatory effects and significance of these three differentially expressed proteins in rush immunotherapy of allergic rhinitis were analyzed and discussed. Method:The serum samples of 15 patients with allergic rhinitis, 15 patients with rush immunotherapy and 10 patients with healthy control group were collected. The samples were studied by isobaric tags for relative and absolute quantitation（iTRAQ） technique. The related differential proteins were determined by two-dimensional gel electrophoresis and mass spectrometry, and the rationality of the screened differential proteins was tested and verified by Cluster3.0 software and Java TreeView software. Finally, the selected CRP, CTHRC1 and WDR89 proteins were identified by enzyme-linked immunosorbent assay（ELISA）. Result:In this study, 893 proteins were detected and 53 differential proteins were identified. Compared with healthy control group, 24 proteins which was statistically significant were found in allergic rhinitis group, which were closely related to the occurrence of allergic rhinitis, including 10 up-regulated proteins and 14 down-regulated proteins. Compared with the allergic rhinitis group, patients with allergic rhinitis underwent 6 days of rush immunotherapy. There were 29 proteins whose expression of proteins with a difference of P value of less than 0.05 and 1.2 times higher, which were related to the effect after the incremental phase of rush immunotherapy was completed, of which 12 were up-regulated and 17 were down-regulated. Compared with healthy control group, the expression of up-regulated of allergic rhinitis group and the expression of down-regulated protein after 6 days of rush immunotherapy were CTHRC1, WDR89; Compared with healthy control group, AR group was down-regulated and the expression of up-regulated protein after 6 days of rush immunotherapy was CRP. CRP, CTHRC1 and WDR89 proteins were identified by enzyme linked immunosorbent assay（ELISA）, and it was found that the differential expression of CTHRC1 and WDR89 in AR and RIT was statistically significant（P<0.05）, but the differential expression of serum CRP in AR and RIT was not statistically significant（P>0.05）. Conclusion:Serum protein CTHRC1 and WDR89 are closely related to the pathogenesis of allergic rhinitis, and played a role in the regulation of rush immunotherapy, while serum protein CRP has no significant effect on AR and RIT.

Identification of continuous immunoglobulin G epitopes of Dermatophagoides farinae allergens by peptide microarray immunoassay.

Dermatophagoides farinae, as a common house dust mite species, is one of the main sources of allergens in the world. At present, Dermatophagoides farinae is found to contain more than 30 groups of allergens. These allergens are used for allergen-specific immunotherapy (AIT) of allergic diseases. During the AIT process, immunoglobulin G (IgG) antibodies can block immunoglobulin E (IgE) antibody-induced allergic reactions in the human body. One of the mechanisms may be that IgG and IgE competitively bind to the same allergic protein, so it is necessary to explore the binding sites (epitopes) of IgG antibodies to allergens. In this study, peptide arrays were constructed to react with the serums from patients with allergic asthma to find the IgG epitopes of several allergens including major allergens (Der f 1, 2) and mid-tier allergens (Der f 4, 5, and 7), and then verified by enzyme-linked immunosorbent assay (ELISA) test. Relevant epitopic sequences were located on the tertiary structure of individual allergens, as reconstructed by homology modeling. One IgG epitope of Der f 1 (90-106aa, NVPSELDLRSLRTVTPI), five IgG epitopes of Der f 4 (61-77aa, ERYQPVSYDIHTRSGDE; 193-209aa, FRSDASTHQWPDDLRSI; 226-242aa, HPFIYHETIYYGGNGIN; 271-287aa, LRWLRNFGTEWGLVPSG; 352-368aa, NDWVGPPTDQHGNILSV), and one IgG epitope of Der f 5 (84-101aa, RYNVEIALKSNEILERDL) were identified. IgG epitopes of Der f 2, 7 were not found. There are overlaps between the IgG and IgE epitopes of Der f 1, 4, and 5. These findings not only reflect the practicality of peptide array and ELISA test in the allergen IgG epitope identification, but also provide more information for further understanding of the human immunological changes during AIT and the molecular mechanisms of IgG blocking IgE activity.

Protocatechuic acid supplement alleviates allergic airway inflammation by inhibiting the IL-4Rα-STAT6 and Jagged 1/Jagged2-Notch1/Notch2 pathways in allergic asthmatic mice.

To clarify the effects of dietary supplementation of protocatechuic acid (PCA) and in-depth mechanisms on allergic asthma in ovalbumin (OVA)-induced mice. Female BALB/c mice were randomly divided into three groups (n = 10 in each group): control group, OVA-induced allergic asthma group, and OVA plus PCA group. Dietary supplementation of PCA was achieved by adding 50mg/kg PCA to AIN 93G diet for 25days. Peripheral blood cells, pulmonary inflammatory cell infiltration, the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), the mRNA levels of Th2-related genes in the lungs, and the protein expressions of the IL-4Rα-STAT6 and the Jagged1/Jagged2-Notch1/Notch2 signaling pathways were measured. Significantly reduced inflammatory cells infiltration and mucosal hypersecretion in the lung tissues, repaired levels of interleukin IL-4, IL-5, and IL-13 in the BALF, and decreased mRNA expression of IL-4, IL-5, and GATA3 were observed in OVA plus PCA group. Moreover, PCA treatment down-regulated the protein levels of IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways. Dietary supplement of PCA alleviated allergic asthma partly through suppressing the IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways in mice. Our study provided the theoretic basis of PCA used as functional food in preventing allergic asthma.

The Role of Der p 23 Sensitization: An Analysis of 474 Patients Sensitized to Mite

Introduction: House dust mite contains several allergen components and causes perennial allergy. Lately, a new major allergen, Der p 23, was described with relatively high sensitization rates in different European Countries. In addition, Der p 23 is supposed to cause asthmatic disease. Objective: We would like to question the prevalence and clinical impact of specific immunoglobulin E to Der p 23 in a large patient sample in southern Bavaria, Germany. Methods: 474 patients from southern Bavaria, who visited the allergy department within the Department of Oto-Rhino-Laryngology of a university hospital, with sensitization to Dermatophagoides pteronyssinus were retrospectively compared regarding their sensitization profile to Der p 1, Der p 2, and Der p 23 and their clinical characteristics. Results: Among D. pteronyssinus-sensitized patients, the overall sensitization rate to Der p 23 was 42% in southern Bavaria. Most likely, patients were simultaneously sensitized to Der p 1, Der p 2, and Der p 23. Der p 23-sensitized patients reported more frequently asthma and showed higher prevalence of poly-sensitization towards 3 additional allergen groups and higher prevalence of double-sensitization to Der p 1 and Der p 2 compared to patients with missing sensitization to Der p 23. Considering the results of allergen provocation tests, neither IgE sensitization against Der p 23 nor levels of specific immunoglobulin E to Der p 23 allow a clear prediction of the clinical relevance of the sensitization. Conclusion: With a sensitization rate of 42%, Der p 23 closely misses the criterion of a major allergen in our southern Bavarian patient collective. A higher prevalence of polysensitization and self-reported asthma was the only clinical feature found in Der p 23-sensitized patients.

Ovomucoid epitope-specific repertoire of IgE, IgG4 , IgG1 , IgA1 , and IgD antibodies in egg-allergic children.

Egg-white ovomucoid, that is, Gal d 1, is associated with IgE-mediated allergic reactions in most egg-allergic children. Epitope-specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG1 , IgG4 , IgA, and IgD) may have a protective function; yet, their epitope-specific repertoires and associations with atopic comorbidities have not been studied. Bead-based epitope assay (BBEA) was used to quantitate the levels of epitope-specific (es)IgA, esIgE, esIgD, esIgG1 , and esIgG4 antibodies directed at 58 (15-mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg-allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities. BBEA had high reliability (ICC >0.75) and low variability (CV <20%) and could detect known IgE-binding epitopes. Egg-allergic children had lower esIgA1 (P=.010) and esIgG1 (P=.016) and higher esIgE (P<.001) and esIgD (P=.015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR =0.48, P=.038). Network analysis identified most associations between esIgE with either esIgG4 or esIgD; indicating that IgE-secreting plasma cells could originate from either sequential isotype switch from antigen-experienced intermediate isotypes or directly from the IgD+ B cells. Collectively, these data point toward a contribution of epitope-specific antibody repertoires to the pathogenesis of egg allergy.

Planning and approach to allergen-specific immunotherapy in polyallergic patients.

Allergy immunotherapy (AIT) is currently the only disease-modifying treatment for allergic-respiratory diseases. Polysensitization may increase the severity of current disease resulting in subsequent asthma development in patients with allergic rhinitis. Due to the absence of general recommendations for the practical approach to polysensitized patients, clinical management is not standardized. The correlation between sensitizations and clinical symptoms, elimination of possible pollen cross-reactivities and principles of homologous allergen groups will guide the allergists to deduce the most relevant allergens for AIT. In the highlight of the previously proposed approach strategies to polyallergic patients, hereby we propose a revised practical stepwise approach based on the current European Medicine Agency (EMA) guidelines. However, more supporting data from well-designed, controlled, future studies are needed to improve clinical management recommendations for AIT in polyallergic patients.

Active free secretory component and secretory IgA in human milk: do maternal vaccination, allergy, infection, mode of delivery, nutrition and active lifestyle change their concentrations?

Free secretory component (free SC) in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion, but its concentration in human milk is unknown. To evaluate the relationship between free SC and SIgA, the influence of maternal factors (vaccination during pregnancy, allergy, previous infections, nutrition, mode of delivery and active lifestyle) on the concentrations of those secretory immune components in human milk was investigated. Concentration of active free SC and SIgA in 124 milk samples from 91 mothers were measured via ELISA. Free SC in milk from Tdap-vaccinated mothers was lower than the Tdap-flu-vaccinated, flu-vaccinated or Rhogam-vaccinated mothers. Free SC in mothers who had a cesarean delivery was higher than mothers who had a vaginal delivery. Free SC in the nonallergic group was higher than the allergic group. Free SC was higher in mothers who rarely/never eat junk food, than in mothers who always/frequently eat junk food. Free SC also was higher in the moderate exercise group (active lifestyle) compared with the group who rarely/never exercise (sedentary lifestyle). Free SC in human milk was not affected by previous maternal infection or probiotic supplementation whereas SIgA was not changed by all investigated maternal factors. This study suggests that active free SC is more impacted by maternal factors than active SIgA in human milk. Active free secretory component (free SC) is more impacted by maternal factors than active secretory IgA (SIgA) in human milk. Vaccination during pregnancy, allergy, nutrition, type of delivery and active lifestyle affect the secretion of free SC in human milk, but not SIgA secretion. Free SC in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion against pathogens and its active concentration in milk strongly varies between mothers, partially due to their specific maternal background.

A dynamic reaction picklist for improving allergy reaction documentation in the electronic health record.

Incomplete and static reaction picklists in the allergy module led to free-text and missing entries that inhibit the clinical decision support intended to prevent adverse drug reactions. We developed a novel, data-driven, "dynamic" reaction picklist to improve allergy documentation in the electronic health record (EHR). We split 3 decades of allergy entries in the EHR of a large Massachusetts healthcare system into development and validation datasets. We consolidated duplicate allergens and those with the same ingredients or allergen groups. We created a reaction value set via expert review of a previously developed value set and then applied natural language processing to reconcile reactions from structured and free-text entries. Three association rule-mining measures were used to develop a comprehensive reaction picklist dynamically ranked by allergen. The dynamic picklist was assessed using recall at top k suggested reactions, comparing performance to the static picklist. The modified reaction value set contained 490 reaction concepts. Among 4234327 allergy entries collected, 7463 unique consolidated allergens and 469 unique reactions were identified. Of the 3 dynamic reaction picklists developed, the 1 with the optimal ranking achieved recalls of 0.632, 0.763, and 0.822 at the top 5, 10, and 15, respectively, significantly outperforming the static reaction picklist ranked by reaction frequency. The dynamic reaction picklist developed using EHR data and a statistical measure was superior to the static picklist and suggested proper reactions for allergy documentation. Further studies might evaluate the usability and impact on allergy documentation in the EHR.

Assessing mortality outcomes of beta-lactam-allergic patients presenting with sepsis

ObjectiveTo determine the impact of reported beta-lactam allergies on in-hospital mortality and other clinical outcomes in patients who presented with severe sepsis or septic shock. MethodsThis single-center, retrospective cohort study was performed at a 35-bed emergency department in central Kentucky. Patients presenting with sepsis, aged 18years or older, were identified between October 2016 and June 2017. Results438 patients with severe sepsis and/or septic shock were identified. Rates of the combined endpoint of in-hospital mortality or transfer to hospice were similar in patients with a beta-lactam allergy (7.2%) versus those with no reported beta-lactam allergy (10.4%) (p=0.41). Time to initiation of antibiotic therapy was slightly longer in the beta-lactam allergic group (2.2h) versus those with no reported beta-lactam allergy (2.15h), but the difference was not statistically significant (p=0.993). Patients were 20.9% more likely to receive an appropriate empiric antibiotic, based off of retrospective culture review, if they did not report a beta-lactam allergy (p=0.009). This led to a delay in effective therapy of 1.59h in the reported beta-lactam allergy arm (p=0.037). ConclusionsAdequate documentation of beta-lactam allergies is vital to ensure timely and appropriate treatment in patients presenting with severe sepsis and septic shock. Choosing alternative treatment options results in increased time to effective antibiotics, reduced likelihood of covering cultures with first antibiotic, and increased total hospital and variable direct cost.

Prevalence of allergic rhinitis in children with otitis media with effusion.

Introduction.The prevalence of allergic rhinitis in children with persistent otitis media with effusion in different countries varies between 82% to 93%. Many risk factors of otitis media with effusion has been studied and proven. However, its association with allergic rhinitis remains controversial. Objective. The main objective of this study is to determine the prevalence of allergic rhinitis in children with persistent otitis media with effusion. This study is also aimed to identify the risk factors of otitis media with effusion, common allergens associated with allergic rhinitis and determine the hearing threshold of children with otitis media with effusion. Methods.A hundred and thirty children were recruited. History taking, physical examination and hearing assessment were done in the first visit. Those with allergic rhinitis underwent skin prick test and treated with intranasal corticosteroid and antihistamine. A second examination and hearing assessment were then repeated after 3 months. Results.The prevalence of allergic rhinitis in children with persistent otitis media with effusion in this study was noted to be 80.3%. Among these children, dust mites appeared to be the most common allergen (87.7%). Another risk factor appeared to be families with more than 4 members per-household (96%). It is noted that that otitis media with effusion caused a hearing loss up to 33 dB. However, there was a statistically significant improvement of the hearing threshold during second visit after commencement of allergy treatment. It was also noted that the hearing threshold in allergic rhinitis group was significantly impaired compared to the non-allergic rhinitis group. Conclusions.Allergic rhinitis and larger family household appeared to be common risk factors in children with persistent otitis media with effusion. There is significant hearing loss noted in children suffering from otitis media with effusion and allergic rhinitis. The hearing threshold improved remarkably with medical therapy. This study hence clarifies the controversy on the association between allergic rhinitis and otitis media with effusion.