Chest Compression Depth Targets in Critically Ill Infants and Children Measured With a Laser Distance Meter: Single-Center Retrospective Study From Japan, 2019-2022.

OBJECTIVES: Current resuscitation guidelines recommend target chest compression depth (CCd) of approximately 4cm for infants and 5cm for children. Previous reports based on chest CT suggest these recommended CCd targets might be too deep for younger children. Our aim was to examine measurements of anterior-posterior chest diameter (APd) with a laser distance meter and calculate CCd targets in critically ill infants and children. DESIGN: A retrospective descriptive study. SETTING: Single-center PICU, using data from May 2019 to May 2022. PATIENTS: All critically ill children admitted to PICU and under 8 years old were eligible to be included in the retrospective cohort. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The chest APd measurements using a laser distance meter are part of our usual practice on the PICU. Target CCd and the over-compression threshold CCd for each age group was calculated as 1/3 and 1/2 of APd, respectively. In 555 patients, the median (interquartile range) of the calculated target CCd for each age group was: 2.7 cm (2.5-2.9 cm), 2.9 cm (2.7-3.2 cm), 3.2 cm (3-3.5 cm), 3.4 cm (3.2-3.6 cm), 3.4 cm (3.2-3.6 cm), 3.6 cm (3.4-3.8 cm), 3.6 cm (3.4-4 cm), and 4 cm (3.5-4.2 cm), for 0, 2, 3-5, 6-8, 9-11, 12-17, 18-23, 24 to less than 60, and 60 to less than 96 months, respectively. Using guideline-recommended absolute CCd targets, 4 cm for infants and 5 cm for children, 49% of infants between 0 and 2 months, and 45.5% of children between 12 and 17 months would be over-compressed during cardiopulmonary resuscitation. CONCLUSIONS: In our cohort, the 1/3 CCd targets calculated from APd measured by laser meter were shallower than the guideline-recommended CCd. Further studies including evaluating hemodynamics during cardiopulmonary resuscitation with these shallower CCd targets are needed.

Cross-reactive epitopes and their role in food allergy.

Allergenic cross-reactivity among food allergens complicates the diagnosis and management of food allergy. This can result in many patients being sensitized (having allergen-specific IgE) to foods without exhibiting clinical reactivity. Some food groups such as shellfish, fish, tree nuts, and peanuts have very high rates of cross-reactivity. In contrast, relatively low rates are noted for grains and milk, whereas many other food families have variable rates of cross-reactivity or are not well studied. Although classical cross-reactive carbohydrate determinants are clinically not relevant, α-Gal in red meat through tick bites can lead to severe reactions. Multiple sensitizations to tree nuts complicate the diagnosis and management of patients allergic to peanut and tree nut. This review discusses cross-reactive allergens and cross-reactive carbohydrate determinants in the major food groups, and where available, describes their B-cell and T-cell epitopes. The clinical relevance of these cross-reactive B-cell and T-cell epitopes is highlighted and their possible impact on allergen-specific immunotherapy for food allergy is discussed.

[A CASE OF FOOD-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS DUE TO POLISHED RICE].

A 14-year-old girl presented to our hospital with food-dependent exercise-induced anaphylaxis (FDEIA), possibly caused by rice. Despite experiencing four previous episodes of suspected FDEIA, she did not seek medical attention at her own discretion. On the fifth occurrence of symptoms, the general practitioner suspected FDEIA and referred the patient to our hospital. The only common factor in all five episodes was the consumption of rice, leading to the examination of the patient under suspicion of FDEIA caused by rice. Skin prick test results were positive for bran and polished rice, and exercise after consumption of polished rice resulted in anaphylaxis. Therefore, we diagnosed FDEIA caused by polished rice. Immunoblotting confirmed the presence of immunoglobulin E reacting with 14-16kDa rice bran protein in the patient's serum. The immunoblot inhibition test suggested that the rice bran protein to which the patient's serum reacted was also present in polished rice and no wash rice. As the patient may experience FDEIA after ingestion of no wash rice or rice flour, she was advised to eliminate these from her diet, treating them similarly to brown rice or polished rice.

Clinical risk factors at 3 months of age for the development of bronchial asthma at 36 months of age.

BACKGROUND: We examined the associations between factors evident at the routine 3-month well-child visit (WCV) and the risk of developing 36-month parent-reported physician-diagnosed bronchial asthma (BA). METHODS: This longitudinal study was conducted in Nagoya City, Japan, and included 40,242 children who qualified for the 3-month WCVs in the city between April 1, 2016 and March 31, 2018. In total, 22,052 (54.8%) questionnaires linked to their 36-month WCVs were analyzed. RESULTS: The prevalence of BA was 4.5%. The multivariable Poisson regression model identified male sex (adjusted risk ratio [aRR], 1.59; 95% confidence interval [CI]: 1.40-1.81), born in autumn (aRR, 1.30; 95% CI: 1.09-1.55), having at least one sibling (aRR, 1.31; 95% CI: 1.15-1.49), wheeze history before 3-month WCVs, with clinic/hospital visit: aRR, 1.99; 95% CI: 1.53-2.56; hospitalization: aRR, 2.99; 95% CI: 2.09-4.12, eczema with itch (aRR, 1.51; 95% CI: 1.27-1.80), paternal history of BA (aRR, 1.98; 95% CI: 1.66-2.34), maternal history of BA (aRR, 2.11; 95% CI: 1.77-2.49), and rearing pets with fur (aRR, 1.35; 95% CI: 1.15-1.58) were independent risk factors for BA at 36 months of age. The combination of severe wheeze history (with clinic/hospital visit or hospitalization) and maternal and paternal BA could identify high-risk infants whose prevalence of BA was 20%. CONCLUSIONS: The combined assessment of important clinical factors enabled us to identify high-risk infants set to derive optimal benefit from health guidance provided to the parent or caregiver of the child or infant at WCVs.

Current situation of anaphylaxis in Japan: Data from the anaphylaxis registry of training and teaching facilities certified by the Japanese Society of Allergology - secondary publication.

BACKGROUND: Anaphylaxis is a potentially fatal severe systemic hypersensitivity reaction that causes symptoms in multiple organs such as the skin, respiratory tract, and gastrointestinal tract; however, no nationwide epidemiological survey on anaphylaxis has been conducted in Japan. This survey aimed to elucidate the triggers and treatment of anaphylaxis in Japan. METHODS: Between February 2015 and October 2017, we prospectively collected clinical data on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology. RESULTS: This study included 79 of the 451 affiliated facilities (18%), and a total of 767 patients were enrolled; 73% of them were aged <18 years and 7% had in-hospital triggers. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. Intramuscular injection of adrenaline was administered therapeutically to 38% of the patients, with 10% requiring multiple doses. Adrenaline auto-injectors were used in 12% of out-of-hospital patients. CONCLUSIONS: The present survey revealed the most common triggers and treatments for anaphylaxis in Japan. Self-management and adrenaline administration as first-line treatment may not be done sufficiently. Therefore, it is necessary to thoroughly educate and train patients and physicians about anaphylaxis.

[ANTIGENICITY OF SOY PROTEIN IN SOY-BASED INFANT FORMULA BONLACT® i].

BACKGROUND: The purpose of this study was to compare the antigenicity of Bonlact® i (BL) with that of defatted soy protein (SP) and soy protein isolate (SPI), which is the original source of BL, using sera from patients with soybean allergy. METHODS: Proteins were extracted from SP, SPI, and BL using PBS. Proteins in each sample were analyzed for antigenicity using inhibition ELISA with SP-specific IgE (sIgE), SDS-PAGE, and immunoblotting. Sere from patients with soybean allergy confirmed by an oral food challenge (OFC) (n=6, OFC+ Pt), and from patients who were positive for soy-sIgE without symptoms ( n = 7, sIgE+ Pt) were used for these assays. The cross-antigenicity of SP and BL with cow's milk (CM) proteins was also analyzed in the sera from patients with CM allergy using inhibition ELISA. RESULTS: SDS-PAGE showed that the proteins in BL produced a smear-like band in the low-molecular-weight region compared with that in SP and SPI. Inhibition ELISA against SP-sIgE showed that BL had a significantly lower inhibition rate than that of SP in both OFC+ Pt and sIgE+ Pt. Immunoblotting analysis showed that the bands of BL were thinner than those of SP and SPI. Additionally, SP and BL showed no cross-antigenicity with CM proteins. CONCLUSION: The proteins in BL was partially digested, and its antigenicity was lower than that of SP and SPI.

Effects of regular soy formula intake between 1 and 2 months of age on food sensitization in infancy.

BACKGROUND: The effects of regular soy formula (SF) intake on the development of food sensitization in infancy remain unclear. This study aimed to assess the effects of regular SF intake between 1 and 2 months of age on food sensitization development by 6 months of age. METHODS: Using data from a randomized controlled trial of a birth cohort from four Japanese hospitals that assessed cow's milk allergy development, we performed a retrospective cohort study of 235 infants who avoided cow's milk formula and supplemented breastfeeding with SF as required between 1 and 2 months of age. Regular SF intake was defined as SF consumption of ≥14 days per month and ≥1350 ml per month. Food sensitization was defined as positive skin prick test reactions to hen's egg, cow's milk, wheat, and/or soy. Using multivariable logistic regression models that adjusted for parental, perinatal, and environmental factors, we calculated the adjusted odds ratios of regular SF intake for food, hen's egg, and cow's milk sensitization by 6 months of age. RESULTS: From the 235 participants, 114 (48.5%) had regular SF intake. The adjusted odds ratios of regular SF intake for food, hen's egg, and cow's milk sensitization were 0.32 (95% confidence interval: 0.16-0.62, p = .0007), 0.42 (0.20-0.88, p = .02), and 0.33 (0.14-0.81, p = .02), respectively. CONCLUSION: Regular SF intake between 1 and 2 months of age in infants avoiding cow's milk formula was significantly associated with a reduced risk of food sensitization in infancy.

Effects of delivery mode and labor duration on the development of food sensitization in infancy.

BACKGROUND: The effects of delivery mode and labor duration on the development of food sensitization (FS) in infancy remain unclear. OBJECTIVE: To elucidate the potential effects of delivery mode and labor duration on FS development by 6 months of age. METHODS: Using data from a randomized controlled trial of a birth cohort from 4 Japanese hospitals that assessed cow's milk allergy development by 6 months of age, we performed a nested case-control trial of 462 participants who had undergone the final assessment at 6 months of age. FS was defined as positive skin prick test reactions to hen's egg, cow's milk, wheat, or soy. For the primary outcome, we calculated the adjusted odds ratio of vaginal delivery (VD) relative to cesarean delivery for FS development by 6 months of age using a multivariable logistic regression analysis. For the secondary outcome, we compared labor durations between participants with and without FS using the Mann-Whitney U test. RESULTS: The adjusted odds ratio of VD for FS development was 2.54 (95% confidence interval, 1.32-4.87; P = .005). The median labor duration was significantly longer in participants with FS (5.7 hours, interquartile range, 2.7-10.1) than in participants without FS (4.5 hours, 1.1-8.2) (P = .01). CONCLUSION: VD was considerably associated with an increased risk of FS in infancy, and longer labor durations may promote FS development.

Randomized trial of early infant formula introduction to prevent cow's milk allergy.

BACKGROUND: Previous research has produced conflicting evidence on the preventive effects of early introduction of cow's milk protein on cow's milk allergy (CMA). OBJECTIVE: Through a randomized controlled trial, we sought to determine whether the early introduction of cow's milk formula (CMF) could serve as an effective strategy in the primary prevention of CMA in a general population. METHODS: We recruited newborns from 4 hospitals in Okinawa, Japan. Participants were randomly allocated to ingest at least10 mL of CMF daily (ingestion group) or avoid CMF (avoidance group) between 1 and 2 months of age. In the avoidance group breast-feeding was supplemented with soy formula as needed. Oral food challenge was performed at 6 months of age to assess CMA development. Continuous breast-feeding was recommended for both groups until 6 months of age. RESULTS: We identified 504 infants for randomization into the 2 groups. In all, the parents of 12 participants declined to receive the intervention, and the study sample comprised 491 participants (242 in the ingestion group and 249 in the avoidance group) for a modified intention-to-treat analysis. There were 2 CMA cases (0.8%) among the 242 members of the ingestion group and 17 CMA cases (6.8%) among the 249 participants in the avoidance group (risk ratio = 0.12; 95% CI = 0.01-0.50; P < .001). The risk difference was 6.0% (95% CI = 2.7-9.3). Approximately 70% of the participants in both groups were still being breast-fed at 6 months of age. CONCLUSIONS: Daily ingestion of CMF between 1 and 2 months of age prevents CMA development. This strategy does not compete with breast-feeding.

A 60-minute dosing interval is safer than a 30- or 40-minute interval in oral food challenge.

BACKGROUND: The interval between antigen ingestion may influence the safety of oral food challenge tests (OFCs), especially in patients with severe food allergies. METHODS: This retrospective chart review of OFCs eliciting objective reactions to wheat, egg, and milk that were performed between April 2012 and January 2021 evaluated an equivalent number of low-dose OFCs performed at 30-, 40-, or 60-min intervals. To avoid the influence of the potential allergy severity of the patients, the prediction scores of all intervals were matched. We evaluated the total symptom score (TS), total ingested dose, and the proportions of severe reactions (TS ≥ 30) and adrenaline use. RESULTS: We analyzed 945 OFCs (wheat, n = 186; egg, n = 561; milk, n = 198). The 60-min OFC had significantly lower TS than the 30- and 40-min OFC methods in wheat (p < 0.001 and p = 0.003, respectively), egg (p < 0.001 for both), and milk (p < 0.001 and p = 0.018, respectively). The total dose in the 60-min method was significantly lower than in the 30-min method (p < 0.001 for all). The proportion of severe reaction (TS ≥ 30) in the 60-min method was significantly lower than that in the 30-min method for the egg and milk OFCs (p = 0.001 and p < 0.001, respectively). There was no difference in the rates of adrenaline injection. CONCLUSIONS: The 60-min interval is safer than 30- or 40-min intervals in wheat, egg, and milk OFCs in patients with a low threshold dose for food allergy.

The clinical cross-reactivity and immunological cross-antigenicity of wheat and barley.

BACKGROUND: Some patients with wheat allergy have been reported to show clinical cross-reactivity to barley. However, it is not clear whether the development of barley allergy in patients with wheat allergy is due to cross-antigenicity between wheat and barley. This study aimed to determine the clinical cross-reactivity and immunological cross-antigenicity of wheat and barley. METHODS: The results of barley oral food challenges (OFCs) were compared before and after oral immunotherapy (OIT) for wheat in nine patients with wheat allergy to estimate the clinical cross-reactivity of wheat and barley. Moreover, we performed enzyme-linked immunosorbent assay (ELISA) inhibition and immunoblotting inhibition using serum from seven patients allergic to wheat and barley. RESULTS: Nine patients who had positive barley-OFC results performed before OIT for wheat were all negative on barley-OFC performed after OIT. In ELISA inhibition, preincubation of serum from patients allergic to wheat and barley with a high barley extract concentration inhibited binding of IgE to wheat extract by less than 10%. On the other hand, wheat and barley extracts equally inhibited binding to barley sIgE at high concentrations. In the immunoblotting inhibition test, the spots of wheat were inhibited but weakly by barley extracts, and most of the spots of barley were inhibited even by low concentrations of the wheat and barley extract. CONCLUSIONS: We showed that barley allergy associated with wheat allergy is caused by cross-reactivity from wheat. The OIT for wheat is one of the promising options for barley allergy.

[COMPARISON OF WHEAL SIZE INDUCED BY BIFURCATED NEEDLE® AND SMARTPRACTICE® PRICK LANCET].

BACKGROUND: There is reportedly a difference in the diameter of the skin reaction induced by different types of skin prick test (SPT) devices. We compared the SPT diagnostic accuracy and wheal size between a Bifurcated Needle® (BN) and SmartPractice® Prick Lancet (PL), which are commercially available in Japan. METHODS: An SPT was performed on 15 adults with and 10 without subjective symptoms of cedar pollinosis who wished to be examined for Japanese cedar pollen (JCP) sensitization. The SPT was performed blindly with a BN or PL with 10mg/ml of histamine dihydrochloride, 50% glycerosaline control, and JCP extract solution (TORII PHARMACEUTICAL CO., LTD., Tokyo, Japan). The wheal sizes induced by the BN and PL were then compared. The JCP-specific IgE antibody titer was measured to compare the sensitivity and specificity of the SPT. RESULTS: Histamine wheal diameters were 6.0 (5.5-6.5) mm by BN and 6.0 (5.5-6.5) mm by PL (p=0.67), and none of the negative control solutions induced wheal. The respective sensitivity and specificity for cedar sensitization were 100% and 86% for BN, 100% and 79% for PL, and the areas under the ROC curve were 0.72 and 0.69 (p=0.32). CONCLUSION: The diagnostic accuracy of cedar pollen extract based on specific IgE-JCP sensitization and the diameter of the wheal produced by a BN and PL were considered equivalent.

[CURRENT SITUATION OF ANAPHYLAXIS IN JAPAN: DATA FROM THE ANAPHYLAXIS REGISTRY OF TRAINING AND TEACHING FACILITIES CERTIFIED BY THE JAPANESE SOCIETY OF ALLERGY].

BACKGROUND: No nationwide epidemiological survey of anaphylaxis in Japan has been conducted. The aim of this study was to elucidate the triggers and treatment of anaphylaxis in Japan. METHODS: We prospectively collected clinical information on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology between February 2015 and October 2017. RESULTS: Seventy-nine of 451 facilities (18%) participated in the study, and a total of 767 patients (under 18 years, 73%; in-hospital, 7%) were enrolled. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. The intramuscular injection of adrenaline in medical institutions accounted for 38% of cases, 10% of which required multiple doses. The rate of use of adrenaline self-injections in out-of-hospital cases was 12%. CONCLUSION: The present study revealed the most common triggers and treatment for anaphylaxis in Japan. Self-management at the onset of anaphylaxis and adrenaline administration as the initial treatment may be insufficient. Therefore, it is necessary to thoroughly instruct patients and educate physicians regarding anaphylaxis.

Purification and molecular characterization of a truncated-type Ara h 1, a major peanut allergen: oligomer structure, antigenicity, and glycoform.

Peanut allergies are among the most severe food allergies, and several allergenic proteins referred to as Ara h 1-Ara h 17 have been identified from peanut seeds. The molecular characterization of Ara h 1 (63 kDa), a glycosylated allergen, has almost been completed, and the occurrence of two homologous genes (clone 41B and clone P17) has been identified. In this study, we found a new variant of Ara h 1 i.e. 54 kDa, in which the N-terminal amino acid sequence was EGREGEQ-, indicating that the N-terminal domain of 63 kDa Ara h 1 had been removed. This new isoform was obtained from the run-through fraction of hydrophobic interaction chromatography while 63 kDa Ara h 1 was tightly bound to the hydrophobic resins, suggesting that the removal of the N-terminal domain resulted in extreme hydrophilic properties. We found that 63 kDa Ara h 1 occurs as higher order homo-oligomeric conformations such as decamer or nonamer, while 54 kDa Ara h 1 occurs exclusively as a homotrimer, indicating that the N-terminal domain of the 63 kDa molecule may be involved in higher order oligomerization. When antisera from peanut-allergic patients were treated with both the Ara h 1 molecules, the immunoglobulin E (IgE) antibodies in these sera reacted with each Ara h 1 molecule, suggesting that the C-terminal as well as the N-terminal domains of Ara h 1 contribute significantly to the epitope formations of this peanut glycoallergen. Furthermore, the glycoform analyses of N-glycans linked to 63 kDa and 54 kDa Ara h 1 subunits revealed that both typical high-mannose type and ß-xylosylated type N-glycans are linked to the molecules. The cross-reactivity of IgE against Ara h 1 in the serum of one peanut allergy patient was completely lost by de-N-glycosylation, indicating the N-glycan of Ara h 1 was the sole epitope for the Ara h 1- specific IgE in the patient.

Exercise-induced allergic reactions after achievement of desensitization to cow's milk and wheat.

BACKGROUND: We have previously reported that more than half of the patients who achieved desensitization after wheat rush oral immunotherapy (OIT) developed exercise-induced allergic reaction on desensitization (EIARD). However, data on EIARDs after slow OIT are lacking. Therefore, this study aimed to investigate the results of exercise provocation tests (EPTs) in patients after slow OIT for cow's milk and wheat allergies. METHODS: This was a retrospective chart review of 87 EPTs in 74 patients. The EPTs were performed in patients who were desensitized to at least 6,600 mg cow's milk protein or 5,200 mg wheat protein with slow OIT and were identified to be at a high risk of EIARDs. EPTs were performed after ingestion of the maximum desensitization dose. The patients' clinical characteristics and symptoms were analyzed. RESULTS: The EPT results were positive for cow's milk in 49% (21/43) of the patients and for wheat in 48% (15/31) of the patients. There was no significant difference in the clinical characteristics between the EIARD-positive and EIARD-negative groups. The specific IgE (sIgE) levels before OIT and the reduction rates of sIgE before and after OIT did not correlate with the outcomes of the EPTs. Among the EIARD-positive patients, 13 patients (cow's milk, n = 7; wheat, n = 6) underwent a second EPT, and the EIARD disappeared in 8 patients (cow's milk, n = 4; wheat, n = 4). CONCLUSION: EIARDs were observed after slow OIT for cow's milk and wheat. Further research into the predictive factors of EIARDs in these patients is needed to understand its clinical manifestations.

Evaluation of cross-reactivity between casein components using inhibition assay and in silico analysis.

BACKGROUND: We previously reported that the specific IgE levels to αs1-casein (CN) and ß-CN in patients with cow's milk allergy decreased with similar dynamics during oral immunotherapy. Therefore, we hypothesized that αs1- and ß-CN have strong cross-reactivity among CN components, despite the low similarity in the full-length amino acid sequences. METHODS: The αs1-, ß-, and κ-CN were purified from commercial cow's milk. We recruited 39 patients with cow's milk allergy, and the serum IgE levels for each CN component were measured by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity between CN components was investigated by competitive ELISA against αs1-CN. Sequence homology between CN components at the peptide level was calculated using in silico analysis and quantified by the property distance (PD) value. RESULTS: The αs1-CN-specific IgE levels exhibited a strong positive correlation with the ß-CN-specific IgE (r = 0.945, P < .001). Complete competition was observed by ß-CN against αs1-CN, suggesting the presence of common epitopes between them. In silico analysis detected 24 peptide sets with PD values lower than 10 between αs1- and ß-CN, and 14 sets between αs1- and κ-CN. The amino acid sequences of αs1-CN (E61-E70) and ß-CN (I12-E21) that showed the lowest PD value (5.30) were present in the characteristic sequence known as casein phosphopeptide (CPP). CONCLUSION: We detected strong cross-reactivity between CN components. Furthermore, we found highly homologous sequences in the CPP region, which contains a core sequence of "SSSEE" with phosphorylated serine residues.

Distinct differences in analytical performance of two commercially available assays for specific IgE to egg white and house dust mite allergens.

BACKGROUND: Measurements of allergen-specific IgE antibodies with different manufacturers' assays show modest or poor agreement. This study compares analytical performance of specific IgE tests for whole allergen extracts and individual allergen components of two assay systems, IMMULITE and ImmunoCAP, using human sera as well as monoclonal antibodies. METHODS: Comparisons were performed for specific IgE to house dust mite (HDM, n = 44), egg white (EW, n = 36) and the allergen components rDer p 1, rDer p 2, nGal d 1, nGal d 2 and nGal d 4 in human sera and with monoclonal mouse/human chimeric IgE antibodies specific for the same allergen components. Competitive interference with IgE measurement was investigated using allergen-specific monoclonal IgG and IgG4 antibodies. RESULTS: Measurements of IgE to HDM and EW in serial dilutions of human sera revealed weaker dilution linearity with IMMULITE than with ImmunoCAP. Analysis of five different monoclonal IgE antibodies with total and specific IgE assays, expected to return similar levels, gave an average specific/total IgE ratio of 0.96 (range 0.71-1.14) with ImmunoCAP and 1.89 (range 0.76-2.85) with IMMULITE, indicating overestimation of specific IgE by IMMULITE. With the EW IgE tests of both assay systems, measurements of a chimeric anti-Gal d 2 IgE antibody were unaffected by a competing mouse IgG antibody. While the same was true for measurement of a chimeric anti-Der p 1 IgE antibody using the HDM test in ImmunoCAP, a suppression of measured concentrations by up to 42% was observed in IMMULITE. Similarly, measurement of HDM-specific IgE in human sera by ImmunoCAP was unaffected by a competing monoclonal anti-Der p 2 IgG4 antibody while IMMULITE displayed a reduction of HDM-specific IgE values by up to 30%. CONCLUSIONS: In this evaluation of analytical performance of two widely used assay systems, ImmunoCAP showed higher accuracy in quantitation of specific IgE and greater resistance against competing allergen-specific non-IgE antibodies which may arise through natural or dietary exposure, or as a result of allergen immunotherapy treatment.

Prevalence and associated factors of wheeze in early infancy.

BACKGROUND: The aim of this study was to assess the prevalence of wheeze in early childhood and to characterize associated factors for wheeze that could identify potentially feasible interventions for the future prevention of wheeze. METHODS: We performed a cross-sectional analysis of the data from the International Study of Asthma and Allergies in Childhood (ISAAC)-modified self-administered questionnaire of parents of 4-month-old infants at well-child visits (mandatory health check-ups) in Nagoya City, Japan, between April 2016 and March 2017 (development dataset) and between April 2017 and March 2018 (validation dataset). We used a multivariable, multilevel analysis to identify significant (P < 0.05), associated factors (Bonferroni correction was applied as necessary) after adjustment for local outbreaks of virus-transmitted diseases, access to medical facilities, and socioeconomic status. RESULTS: Among the 20 362 questionnaires given to families of infants living in Nagoya City (development dataset), 19 104 questionnaires (93.8%) were analyzed after data cleaning. In all, 1,446 (7.6%) infants experienced wheeze at least once within 4 months of age, 991 (5.2%) visited the clinic/hospital with wheeze, and 244 (1.3%) underwent hospitalization at that time. In the multilevel, multivariable model for hospitalization with wheeze, significant associated factors were male sex (adjusted odds ratio 1.8; 95% confidence interval 1.4-2.3), maternal current smoking (3.3; 2.0-5.5), and having at least one sibling (3.0; 2.2-4.1). These factors were also associated with wheeze and clinic/hospital visit with wheeze, and the results were confirmed in the validation dataset. CONCLUSIONS: Our study highlights that smoking cessation among mothers and improved hand hygiene at home are two interventions that could potentially decrease wheeze in early infancy.

Comprehensive hospital-based regional survey of anaphylaxis in Japanese children: Time trends of triggers and adrenaline use.

BACKGROUND: Since few studies have analyzed time trends in pediatric anaphylaxis, including triggers and adrenaline usage, this study aimed to reveal these issues in a comprehensive analysis of pediatric anaphylaxis cases. METHODS: The Aichi Medical Association performed a comprehensive survey of pediatric anaphylaxis cases aged under 15 years from 87 secondary and 25 tertiary emergency care hospitals in Aichi Prefecture (population 7.5 million), Japan. RESULTS: Between April 2016 and March 2020, 3423 cases of anaphylaxis were identified. Food items were the most frequent trigger (73%), followed by exercise after food ingestion (4.3%), and drugs (2.2%). Egg (19%) and milk (17%) specifically were the most frequent among food triggers, while the largest proportional increase was observed in tree nuts from 6.0% in 2017 to 15% in 2019. Overall, 1647 (48%) cases were admitted to the hospital, of which 26 (0.8%) were admitted to the intensive care unit. Drug-induced anaphylaxis was associated with the highest admission rate (71%). Of the 2493 food-induced anaphylaxis cases, 1107 (44%) were treated with adrenaline. Among them, 343 cases included previously prescribed adrenaline auto-injectors (AAI), with 225 (66%) usages prior to hospital arrival. There was no significant difference in the admission rate between the cases in which AAIs were used and those with adrenaline administered in the hospital (68% and 72%, respectively). CONCLUSIONS: The proportion of tree nuts in food-induced anaphylaxis increased significantly. Although prehospital AAI use has become widespread, it was not associated with lower admission rate compared to in-hospital adrenaline usage.

Efficacy, safety, and parental anxiety in a randomized trial of two dietary instruction methods for children with suspected hen's egg allergy.

BACKGROUND: Little has been reported on how to introduce hen's egg into the diet of children with suspected egg allergy. We compared the efficacy, safety, and parental anxiety of two different dietary instruction methods to introduce egg. METHODS: Eligible participants were children aged 1-4 years who were positive for egg white IgE, and ovomucoid IgE <3.5 kUA/L. Participants were either naïve in egg consumption or had a history of an immediate, but non-anaphylactic, allergic reaction to egg. After a negative result of baseline 2 g boiled egg white oral food challenge (OFC), participants were randomly assigned to the step-up OFC testing (SOFT) or home incrementing group. The primary outcome was the proportion of participants who were able to ingest 20 g of boiled egg white 6 months after initiation. This study is registered with the University Hospital Medical Information Network clinical trial registry (UMIN000024192). RESULTS: Between September 2016 and August 2018, we randomly allocated 55 participants to the SOFT (n = 33 [60%]) and home incrementing (n = 22 [40%]) groups and analyzed 51 patients. Four patients were excluded because they were lost to follow-up. Thirty-one (96.9%) of 32 participants in the SOFT and 12 (63.2%) of 19 in the home incrementing group achieved the primary outcome (p = 0.003). No serious adverse reactions were observed in either group. Parental anxiety significantly improved during treatment in both groups. CONCLUSIONS: The SOFT method was more effective than home incrementing as dietary instruction to introduce egg in children with suspected egg allergy.