Clinical Features of Quail Egg Ingestion in Patients with Acquired Tolerance to Hen Eggs: A Case Series Study.

INTRODUCTION: Patients with hen's egg allergy are often instructed to avoid consuming other avian eggs, such as quail eggs. However, it is unclear whether patients with an acquired tolerance to hen eggs continue to avoid consuming quail eggs. This study aimed to evaluate the clinical features of quail egg ingestion. METHODS: This prospective case series included children aged ≥1 year with hen's egg allergy who were recruited between October 2019 and February 2021 in our hospital. We conducted an oral food challenge (OFC) with three boiled quail eggs to evaluate the clinical features of quail egg ingestion in patients with acquired tolerance to hen eggs. The primary outcome was a positive OFC after ingesting three quail eggs. Secondary outcomes were cross-antigenicity between hen and quail eggs observed through the skin prick test (SPT) and pattern of quail egg allergy, comprising the onset of reaction, and severity. The correlation between the diameters of the wheals with SPT in hen and quail eggs was evaluated using the Pearson product-moment correlation coefficient. RESULTS: A total of 62 patients underwent the quail egg OFC. The median (interquartile range) age of the participants was 3 (2-5) years. Thirty-three (53%) patients had a history of anaphylaxis due to hen eggs. The median total immunoglobulin E (IgE) level in patients who underwent the OFC with half a heated whole hen's egg was 271 (98-593) IU/mL. The median specific IgE level in egg white and ovomucoid was 9.7 (3.2-21.5) and 4.4 (1.3-6.9) UA/mL, respectively. The quail egg OFC results revealed that none of the 59 patients who ate the three quail eggs completely had an allergic reaction. The SPT-positive and SPT-negative rates in raw and boiled hen and quail egg whites were both correlated. The diameters of wheals with SPT in raw hen and quail egg whites and yolks were positively correlated. CONCLUSION: Patients with an acquired tolerance to hen eggs may not be required to avoid consuming quail eggs.

[BULLYING IN JAPANESE CHILDREN AND ADOLESCENTS WITH FOOD ALLERGIES].

OBJECTIVE: To elucidate the prevailing circumstances of victimization, including bullying, faced by children afflicted with food allergies in Japan. METHODS: From July to August 2021, we executed a web-based questionnaire survey targeting children with food allergies enrolled in the fourth grade or higher, who sought medical attention at the Department of Pediatrics in Showa University Hospital or were affiliated with three allergy-focused patient associations. The survey aimed to ascertain whether these children had encountered instances of bullying, the nature of the bullying incidents, and whether such acts of bullying triggered allergic symptoms. RESULTS: A total of sixty-six children with food allergies participated in the survey. Among them, forty-five (68%) were male, thirty-three (50%) were attending elementary school, and thirty-five (53%) reported experiencing some form of victimization throughout their lives. Specifically, fourteen (21%) had been subjected to bullying due to their food allergy, with two children being coerced into consuming allergens and one child experiencing symptoms induced by allergen-based bullying. CONCLUSION: It is evident that a significant number of children with food allergies face bullying. Therefore, it is imperative for healthcare providers and parents to acknowledge the inherent risk of bullying as an integral aspect of caring for children with food allergies. Prompt measures should be taken, such as educating both teachers and non-allergic children about this risk.

[INVESTIGATION OF THE IMPACT OF ALLERGIC DISEASE ON CHILDREN'S SARS-CoV-2 VACCINATION DECISIONS].

Background, Objectives: The factors associated with parents' decisions to vaccinate their children with SARS-CoV-2 vaccine and the impact of the coexistence of allergic diseases in their children are unclear. METHODS: A cross-sectional survey was conducted among parents of patients aged 15 years or younger who visited our pediatric allergy outpatient clinic and three partner pediatric clinics between April and May 2021. Survey items included presence or absence of other allergic diseases, and SARS-CoV-2 vaccination preferences and reasons. RESULTS: 646 responses were received, with 568 valid responses (88%). Thirty-eight respondents (6.7%) did not want their children to receive SARS-CoV-2 vaccine. Factors that led parents to reject the SARS-CoV-2 vaccine for their children were the coexistence of food allergies and a low evaluation of the expectations of the safety and preventive effect of the SARS-CoV-2 vaccine. The top reasons for not wanting to vaccinate were related to concerns about side effects to the vaccine. CONCLUSION: In order for parents to make correct decisions regarding SARS-CoV-2 vaccination of their children, it is necessary to create an environment in which up-to-date and correct information is available to avoid excessive anxiety. More care is needed, especially if the child has food allergies.

Relationship between the diagnosis of food protein-induced enterocolitis syndrome and postemetic procalcitonin levels.

Background: There are no reports on the relationship between food protein-induced enterocolitis syndrome (FPIES) diagnosis and procalcitonin levels. Objective: Our study sought to demonstrate a correlation between the presence or absence and severity of FPIES symptoms and postemetic procalcitonin levels. Methods: The subjects were 53 patients with FPIES (44 with hen's egg allergy, 4 with milk allergy, 4 with wheat allergy, and 3 with soy allergy), who collectively underwent a total of 75 oral food challenges (OFCs). Procalcitonin levels at 5 hours after antigen ingestion were compared between patients with a positive OFC result and those with a negative OFC result and between patients who experienced mild or moderate events and those who experienced severe events. Results: At 5 hours after ingestion of the causative food, the median procalcitonin levels in patients with a negative OFC result, patients who experienced a mild or moderate event, and patients who experienced a severe event were 0.02, 0.03, and 0.16 ng/mL, respectively. The procalcitonin level was significantly higher in the groups with a positive OFC result than in the groups with a negative OFC result (P < .001), and it was significantly higher in those who experienced severe events than in those who experienced mild or moderate events (P = .012). Conclusion: Measurement of procalcitonin levels has the potential to provide a quantitative and objective assessment of FPIES diagnosis and severity.

Optimal period for achieving sustained unresponsiveness in peanut oral immunotherapy.

Background: Oral immunotherapy (OIT) can help children with persistent food allergies achieve sustained unresponsiveness (SU). However, the optimal therapeutic period for obtaining SU remains unclear. Objective: We aimed to retrospectively investigate the association between the OIT treatment period and achievement of SU. Methods: We enrolled patients who received OIT for peanut allergy between January 1, 2018 and December 31, 2022. OIT comprised the build-up phase, maintenance phase, complete avoidance, and an oral food challenge (OFC) for confirming SU. The peanut dose in the OFC was gradually increased to 3,000 mg (peanut protein: 795 mg), which was subsequently maintained for ≥5 months. SU was defined as a negative response to 795 mg of peanut protein after ≥2 weeks of complete avoidance. We evaluated the therapeutic OIT period for achieving SU using Kaplan-Meier analysis. Results: Forty-eight patients underwent peanut OIT. The starting age at OIT initiation was 8 (interquartile range [IQR], 7-10) years. Forty-one (85%) patients had a history of anaphylaxis. The median specific immunoglobulin E concentration to peanut and Ara h 2 at OIT initiation was 85.3 (IQR, 33.7-100) and 57.6 (IQR, 21.9-100) UA/mL, respectively. The median observational period was 2.1 (IQR, 1.6-3.0) person-years (PY). Thirty-four (71%) patients achieved SU, with the rate of SU achievement gradually increasing with the therapeutic period. The median period until SU achievement was 2.1 (95% confidence interval, 1.6-2.5) PY. The rate of SU achievement slowed down after 2.7 PY. Conclusion: OIT for at least 2.7 PY can increase the rate of SU achievement. The protocol No. 3107.

Reproducibility of food challenge to cow's milk: Systematic review with individual participant data meta-analysis.

BACKGROUND: Cow's milk (CM) is an increasingly common cause of severe allergic reactions, but there is uncertainty with respect to severity of reactions at low-level CM exposure, as well as the reproducibility of reaction thresholds. OBJECTIVE: We undertook an individual participant data (IPD) meta-analysis of studies reporting double-blind, placebo-controlled food challenges in CM to determine the rate of anaphylaxis to low-level exposures and the reproducibility of reaction thresholds. METHODS: We performed a systematic review and IPD meta-analysis of studies reporting relevant data. Authors were contacted to provide additional data and/or clarification as needed. Risk of bias was assessed using the National Institute for Clinical Excellence methodologic checklists. RESULTS: Thirty-four studies were included, representing data from over 1000 participants. The cumulative ED01 and ED05 (cumulative doses causing objective symptoms in 1% and 5% of the at-risk allergic population) were 0.3 (95% confidence interval [CI], 0.2-0.5) and 2.9 (95% CI, 1.6-5.4) mg, respectively. At meta-analysis, 4.8% (95% CI, 2.0-10.9) and 4.8% (95% CI, 0.7-27.1) of individuals reacting to ≤5 mg and ≤0.5 mg of CM protein had anaphylaxis (minimal heterogeneity, I2 = 0%). Then 110 individuals underwent repeat double-blind, placebo-controlled food challenges; the intraindividual variation in reaction threshold was limited to a ½-log change in 80% (95% CI, 65-89) of participants. Two individuals initially tolerated 5 mg CM protein but then reacted to this dose at a subsequent challenge, although neither had anaphylaxis. CONCLUSIONS: About 5% of CM-allergic individuals reacting to ED01 or ED05 exposure might have anaphylaxis to that dose. This equates to 5 and 24 anaphylaxis events per 10,000 patients exposed to an ED01 or ED05 dose, respectively, in the broader CM-allergic population. Most of these anaphylactic reactions would be mild and respond to a single dose of epinephrine.

Evaluation of early laryngeal reaction at oral food challenge.

Background: Open oral food challenge (OFC) is a commonly used diagnostic method for food allergy; however, the occurrence of uncertain reactions leads to inconclusive results. Objective: We aimed to determine the associations between mild laryngeal symptoms and positive results in open OFCs. Methods: We retrospectively investigated medical records of high-risk children (aged 3-15 years) who had undergone open OFC for a low dose of peanuts, hen's egg, cow's milk, or wheat. The OFC result, severity of allergic reactions, and administered treatments during OFCs were compared between the subjects with and without laryngeal symptoms. The risks of a positive OFC result were assessed by using logistic univariate and multivariate analyses, with age, sex, and serum levels of total and food-specific IgE as covariates. Results: Among the 198 patients who underwent OFC, 25 had mild laryngeal symptoms: 8 (32%), 7 (22%), 0 (0%), and 10 (40%) in the OFC trials with hen's egg, cow's milk, wheat, and peanuts, respectively. In the peanut OFCs, univariate analyses revealed a 5-fold higher risk of a positive result (odds ratio = 5.0 [95% CI = 1.1-22.8]) in the symptomatic subjects than in the asymptomatic subjects. However, on multivariate analyses, none of the associations between the symptoms and a positive result were significant in any of the OFCs. The occurrence of anaphylaxis and adrenalin injections did not differ significantly between the symptomatic and asymptomatic subjects. Conclusions: Laryngeal symptoms should be considered a warning sign for a positive OFC result in peanut OFCs, although not critical enough to stop the challenge.

Is oral food challenge test useful for avoiding complete elimination of cow's milk in Japanese patients with or suspected of having IgE-dependent cow's milk allergy?

BACKGROUND: Cow's milk, along with hen's egg, are common causes of food allergies in children worldwide. Accidental ingestion of milk is common and often induces severe allergic reactions. Oral food challenge test (OFC) is usually performed in patients with or suspected of having a food allergy. However, the evidence of whether cow's milk OFC is useful in IgE-dependent cow's milk allergy patients to avoid total elimination is not known. METHODS: After setting the clinical question and outcomes, we performed a systematic review for relevant articles published from January 1, 2000 to August 31, 2019 using PubMed® and Ichushi-Web databases. Each article was then evaluated for the level of evidence. All positive results of the OFC were defined as adverse events. RESULTS: Forty articles were selected in this study. Our review revealed that cow's milk OFC was able to avoid the complete elimination of cow's milk in 66% of the patients with cow's milk allergy. We also found that adverse events occurred frequently (50.5%). CONCLUSIONS: This analysis supports the recommendation of conducting cow's milk OFC to avoid complete elimination of cow's milk, however the test should be conducted with careful consideration of the patient's safety. As the methods of OFC and subjects varied among the articles selected in this study, further studies are needed to obtain higher quality evidence.

Phylogeny and taxonomy of Phyllactinia species (powdery mildew: Erysiphaceae) occurring on the ash trees (Fraxinus spp.).

The genus Fraxinus (Oleaceae), known as ash trees, currently comprises 43 recognized species that are distributed in temperate and subtropical regions of the Northern Hemisphere. Two Phyllactinia species, P. fraxini and P. fraxinicola, have been known on Fraxinus spp. so far. In this study, powdery mildews belonging to Phyllactinia were collected on Fraxinus spp. from different areas of the world to make molecular and morphological analyses. These specimens are divided into four distinct molecular phylogenetic groups, which are distinguishable by their morphology and/or host preference. Two new species, viz. P. japonica occurring on F. sieboldina and F. lanuginosa f. serrata, and P. fraxini-longicuspidis on F. longicuspis, are proposed in this study. An epitype is designated for P. fraxini. This study indicates very high host specificity among the four Phyllactinia species on Fraxinus, suggesting that genetic isolation by host specificity played a more important role than geographic segregation in the speciation events of these Phyllactinia species. Evolutionary timing calculated by molecular clock analysis suggests that these powdery mildews diverged in accordance with host phylogeny after divergence of host plants.

Effect of oral immunotherapy in children with milk allergy: The ORIMA study.

BACKGROUND: This study was aimed at evaluating the efficacy and safety of oral immunotherapy (OIT) in children with severe cow's milk allergy. METHODS: The subjects comprised 28 children (aged 3-12 years) with allergic symptoms that were induced by ≤ 10 mL of cow's milk in an oral food challenge test (OFC). The subjects were randomly allocated to the treatment group (n = 14) and control group (n = 14); the former received rush immunotherapy for 2 weeks, followed by a gradual increase of cow's milk volume to 100 mL for 1 year, and the latter completely eliminated cow's milk for 1 year. Both groups underwent an OFC with 100 mL of cow's milk after 1 year. RESULTS: The treatment group had significantly higher rates of a negative OFC [7/14 (50%) vs. 0/14 (0%), p < 0.01] compared with the control group. The cow's milk-specific IgE level significantly decreased in the treatment group (p < 0.01) but not in the control group (p = 0.63). During the study period, adrenaline was required in 6/14 patients (43%) of the treatment group and in 0/14 patients (0%) of the control group. Long follow-up data were available at the 2-year point after the study for 8 in the treatment group and 7 (87.5%) of these continued to ingest milk (>100 mL). CONCLUSIONS: The effect of immunotherapy was 50%, but the incidence of adverse events was not low. Further studies focusing on safety is necessary to standardize OIT for cow's milk allergy.

Utility of therapeutic strategy based on the modified Pulmonary Index Score for childhood asthma exacerbation.

Background: There are no validated quantitative tools for assessing asthma exacerbation, which may cause significant variation in determining the severity of exacerbation across caregivers. A modified Pulmonary Index Score (mPIS) has been proposed as a quantitative indicator of the severity of childhood asthma exacerbation. However, the utility of mPIS as a treatment decision-making tool has not been investigated. Objective: The aim of the present study was to clarify the utility of therapeutic strategies based on mPIS in children hospitalized for asthma exacerbation. Methods: This was a case-control study of patients admitted to our hospital between 2010 and 2015. In addition to the conventional therapy based on Japanese guidelines, treatment adaptation by using mPIS began in 2013. Children admitted after 2013 were regarded as being in the case group and those before 2012 were the control group. The length of the hospital stay and the duration of continuous isoproterenol inhalation therapy (CIT) were compared as clinical outcomes. Results: The targeted number of patients was 346 (182 cases and 164 controls). The mean ± standard error age was 3.5 ± 0.2 years in the case group and 3.4 ± 0.2 years in the control group. Male patients constituted 64.3% of the case group and 60.4% of the control group. The mean ± standard error length of hospital stay was significantly shortened in the case group (8.1 ± 0.2 days versus 9.6 ± 0.2 days, p < 0.001). The mean ± standard error duration of CIT was also shortened in the case group (2.3 ± 0.1 days versus 3.9 ± 0.3 days, p < 0.001). Conclusion: An mPIS-based therapeutic strategy may have reduced the length of hospital stay by enabling timely adjustments to clinical interventions and enabling caregivers to perform a more-accurate assessment of asthma exacerbation.

Blood folate concentrations analyzed by microbiological assay and chemiluminescent immunoassay methods.

A limited number of studies have been available to compare blood folate concentrations by the microbiological assay (MA) method with those using the chemiluminescent immunoassay (CLIA) method. We compared folate concentrations measured by Lactobacillus rhamnosus MA with those measured by CLIA (Access Immunoassay Systems) in human plasma/serum and erythrocytes pairs (n=35). The mean plasma folate by MA was significantly higher than that by CLIA (p<0.0001), whereas the mean erythrocyte folate by MA was significantly lower than that by the CLIA method (p<0.001). Plasma folate by MA significantly correlated with serum folate by CLIA (r=0.85, p<0.001). Similarly, the correlation between erythrocyte folate measured by MA and CLIA methods was significant (r=0.87, p<0.001). We conclude that folate concentrations obtained by CLIA are different from those obtained by MA, suggesting that it is undesirable for inter-laboratory comparisons when folate values are obtained by different methods. Although we evaluated only one CLIA method, we recommend careful evaluation of folate assay by each CLIA method before the use in clinical and research settings.

A validated HPLC-fluorescence method with a semi-micro column for routine determination of homocysteine, cysteine and cysteamine, and the relation between the thiol derivatives in normal human plasma.

A semi-micro column HPLC-fluorescence method for routine determination of thiol derivatives such as homocysteine (Hcy), cysteine (Cys) and cysteamine (CA) is described. The thiol derivatives labeled with ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F) were isocratically separated within 12 min on a semi-micro ODS column (Daisopak-SP-120-5-ODS-BP) with a mixture of 25 mm acetate buffer (pH 2.00) and CH(3)CN as a mobile phase. The purity and similarity of SBD-thiols by a multi-wavelength fluorescence detector were more than 92.3 and 96.7%. The detection limits of Hcy, Cys and CA at a signal-to-noise ratio of 3 were 0.16, 0.47 and 0.03 microm, respectively. Furthermore validation parameters such as accuracy, precision and robustness of the proposed method showed satisfactory results. Almost 850 plasma sample injections (range 572-1076, n = 3) for a column could be performed without differences in retention time and peak heights of labels. As an application of the proposed method, the determination of thiol derivatives in normal human plasma (n = 103) was demonstrated. The correlation coefficients between Hcy vs Cys and Hcy vs CA were 0.38 and -0.35, respectively.