Development and validation of a new asthma questionnaire to help achieve a high level of control in school-age children and adolescents.

BACKGROUND: Maintaining good asthma control minimizes the risk of exacerbations and lung function decline and is a primary goal of asthma management. The Japanese Pediatric Asthma Guidelines (JPGL) employs different classification criteria for control status from other guidelines, stressing a higher level of control. Based on JPGL, we previously developed a caregiver-completed questionnaire for assessing and achieving best asthma control in preschoolers. In this study, we aimed to develop a questionnaire for school-age children and adolescents. METHODS: A working questionnaire comprising 14 items for patients and 34 items for caregivers was administered to 362 asthma patients aged 6-15 years and their caregivers. Separately, physicians filled out a questionnaire to determine JPGL-defined control. Logistic regression analysis was performed to construct a model to predict control levels using data from a randomly selected set of completed questionnaires from two-thirds of the subjects. Validation was performed using the remaining questionnaires. RESULTS: A set of 7 questions, encompassing self-assessed control status at the time of the visit and in the past month, and nocturnal/early morning asthma symptoms for patients and frequency of asthma symptoms, dyspnea, rescue beta-agonist use, and asthma hospitalization for caregivers, were selected and the 7-item model showed a good statistical fit with AIC of 110.5. The model has been named the Best Asthma Control Test for School Children and Adolescents (Best ACT-S). Best ACT-S scores differed significantly in the hypothetical direction among the groups of different JPGL-defined control levels, step-up/down treatment decisions, and presence/non-presence of exacerbations in the previous year. CONCLUSIONS: The Best ACT-S is a valid questionnaire for children/adolescents aiming for best asthma control.

Development of an Oral Immunotherapy-Related Parental Burden Scale.

INTRODUCTION: Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems. This study modified OIT-PB and verified its reliability and validity. METHODS: A 20-item draft covering the physical and mental burdens caused by OIT was prepared jointly with multiple allergists. The Food Allergy Quality of Life Questionnaire-Parental Burden (FAQLQ-PB) and Stress Response Scale-18 (SRS-18) were used to verify concurrent validity. A questionnaire survey was administered during treatment to parents of FA children who had started OIT for the first time. An additional OIT-PB survey was performed at one specific institution 1 week after the posttreatment survey. RESULTS: The responses of 64 of the 76 recruited parents were analyzed. Of the 20 questions, 1 item was excluded owing to the floor effect, 1 was excluded because its commonality was less than 0.2, and 2 were excluded because their factor loading values were less than 0.4. Factor analysis was used to classify the OIT-PB into the following 4 subscales: "burden caused by adherence to treatment plan," "anxiety about symptom-induced risk," "burden due to patient's eating behavior," and "anxiety about treatment effect." The Cronbach's α for all 16 items of the OIT-PB was 0.893; Cronbach's α for each subscale was 0.876, 0.898, 0.874, and 0.717. The re-test reliability coefficient was 0.864 (95% confidence interval [CI]: 0.720-0.937, p < 0.001). A significant positive correlation was found between the OIT-PB and FAQLQ-PB (R = 0.610 [95% CI: 0.422-0.747], p < 0.001) and the SRS-18 (R = 0.522 [95% CI: 0.306-0.687], p < 0.001). A significant negative correlation was found between the rate of increase in OIT food intake and the "anxiety about treatment effect" score (R = -0.355 [95% CI: -0.558-0.112], p < 0.001). Parents of children on the hen's egg OIT treatment scored higher on the "burden due to patient's eating behavior" subscale than did parents of children on the milk and wheat OIT treatment. CONCLUSION: The burden of OIT experienced by parents can be broadly classified into four categories. The modified OIT-PB was able to evaluate them individually and was shown to have reliability and validity. This scale is expected to be useful in the development of OIT that considers not only therapeutic effect but also the burden experienced by FA children and their parents.

Efficacy and safety of low- and high-dose slow oral egg immunotherapy for hen's egg allergy: Single-center non-inferiority randomized trial.

BACKGROUND: Low-dose oral immunotherapy (OIT) is a safe treatment for hen's egg allergy; however, comparison of its therapeutic effects with those of high-dose OIT has not been reported. OBJECTIVE: To compare the efficacy of low- and high-dose boiled egg-white (EW) OIT for hen's egg allergy. METHODS: Patients with hen's egg allergy were randomly assigned to two groups: OIT using hard-boiled EW with a maximum maintenance dose of 2 and 20 g in the low-dose (L-D) and high-dose (H-D) groups, respectively. The intake dose was ingested twice a week, increased by approximately 20% per week until reaching the target maintenance dose (2 or 20 g hard-boiled EW), and maintained thereafter according to the schedule. The threshold was confirmed via oral food challenge (OFC) after 6 months, and the difference in the proportion of subjects passing the exit OFC between groups was evaluated. RESULTS: Fifty-two patients (L-D, n = 23; H-D, n = 29) were enrolled. Thirty-three patients (L-D, n = 17; H-D, n = 16) completed the 6-month OIT and underwent an exit OFC. In total, three (L-D, 3/17; H-D, 3/16) patients in each group tested negative for an exit OFC with a 20-g reactive dose (p = 1.000). EW-specific IgE levels in both groups decreased significantly after OIT (L-D, p < 0.001; H-D, p = 0.002). CONCLUSIONS: A threshold-elevating effect was observed in the L-D group, not inferior to that in the H-D group. Low-dose OIT may be appropriate to treat hen's egg allergy for the first 6 months.

[OBJECTIVE EVALUATION OF SUBLINGUAL IMMUNOTHERAPY FOR PEDIATRIC ALLERGIC RHINITIS RESPOND TO SQ HOUSE DUST MITE].

BACKGROUND: Sublingual immunotherapy (SLIT) has become applicable to insurance for children in Japan in 2018. However, as for the efficacy of SLIT for children, objective evaluation methods have not been sufficiently investigated. SUBJECTS AND METHODS: We investigated the efficacy of SLIT as both subjective and objective evaluation in 44 children with allergic rhinitis sensitized to house dust mite who started the treatment in the summer of 2018 in our hospital. The children and their patients wrote the allergy diary every day, and in winter/spring/summer vacations, they answered Japanese allergic rhinitis quality of life standard questionnaire and were evaluated with nasal provocation test, blood test, rhinomanometry for 3 years. RESULTS: 29 (66%) of the 44 children continued SLIT for 3 years. Symptom scores, QOL scores, symptom medication scores halved in a year and the effect lasted in the second and third year. Nasal provocation test and rhinomanometry showed significant improvement. Specific IgE increased transiently and then decreased. Specific IgG4 increased annually. CONCLUSION: The present study showed a decrease in scores not only for subjective assessments but also for objective evaluation methods, the house dust nasal provocation test and the nasal airway resistance.

[LUNG FUNCTION IN EARLY-PERIOD SCHOOL-AGED ASTHMATIC CHILDREN MAY BE A PREDICTOR OF TREATMENT LEVEL AT ADOLESCENCE].

BACKGROUND: Lung function in early-period school-aged children with asthma influences remission in adolescence. However, there are no reports of this in Japan. OBJECTIVE: This study investigated the influence of lung function in early-period school-aged asthmatic children on medication during adolescence. SUBJECTS AND METHODS: Forty-nine subjects who had visited our hospital at age 6 years or younger were evaluated on March 31, 2018, at the ages of 16 to 18, to determine their asthma treatment step (step 1 to 4). The patients were divided into four groups, and lung function at six years old. RESULTS: The groups for steps 1, 2, 3 and 4 had 11, 13, 6, and 8 participants, respectively. FEV1.0% at six years old for step 1, 2, 3 and 4 had 88.4%, 89.1%, 86.9%, 80.9%, and %V50 had 111.5%, 107.9%, 108.2% and 69.9%, respectively. There were significant differences between the groups of step 4 and 1, 2 regarding FEV1.0% and %V50. CONCLUSION: As for the patient of treatment step 4 of adolescence, lung function decreased at 6 years old in comparison with step 1, 2 patients. Lung function in early-period school-aged asthmatic children may predict the treatment level at adolescence.

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study.

INTRODUCTION: The severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020. METHODS: All patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients' records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software. RESULTS: Data from 61 patients (16 Pt-CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt-CSI were significantly older and had hypertension or diabetes than Pt-MMI (P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt-CSI than in Pt-MMI (P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt-CSI than in Pt-MMI (P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt-CSI than in Pt-MMI (P = 0.013). Among the 16 Pt-CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died. CONCLUSIONS: The illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.

Relationship between the outcome of low-dose egg oral immunotherapy and the fold-difference levels of allergen-specific IgE and IgG4 in serum.

BACKGROUND: There are no indices to monitor desensitization by low-dose egg oral immunotherapy (eOIT). OBJECTIVE: We aimed to examine the relationship between desensitization by low-dose eOIT and the changes in allergen-specific immunoglobulin E (IgE) and IgG4 levels. METHODS: We carried out low-dose eOIT in 31 patients with severe egg allergy in our previous two studies. After 4 months of treatment, the patients with no observed allergic symptoms in response to the open hard-boiled egg white challenge tests were classified as the negative group, and the remaining patients, the positive group. The fold-difference levels were calculated using 10 Log (Titer after eOIT/Titer before eOIT). RESULTS: The 28 patients who completed eOIT with sufficient serum collected before and after eOIT were analyzed. The median fold-difference levels of ovomucoid-specific IgE in the negative and positive groups were 0.819 and 0.953, respectively (P = 0.082). The median fold-difference levels of ovalbumin-specific IgG4 in the negative and positive groups were 2.01 and 1.29, respectively (P = 0.057). In the receiver-operating characteristic curves, the area under the curves of fold-difference ovomucoid-specific IgE and ovalbumin-specific IgG4 were 0.701 and 0.719, respectively. The challenge positive predictive values of fold-difference ovomucoid-specific IgE and ovalbumin-specific IgG4 were 83.8% (cut-off point: 0.934) and 77.8% (cut-off point: 1.87), respectively. Moreover, the challenge positive predictive value in patients with both 0.934 < ovomucoid-specific IgE and ovalbumin-specific IgG4 <1.87 was 100%. CONCLUSIONS: The fold-difference levels of allergen-specific IgE and IgG4 in serum are considered useful for monitoring desensitization by low-dose OIT.

Single-Center Noninferiority Randomized Trial on the Efficacy and Safety of Low- and High-Dose Rush Oral Milk Immunotherapy for Severe Milk Allergy.

INTRODUCTION: Oral immunotherapy (OIT) has been reported to be effective but associated with a risk of severe symptoms. Thus, an OIT method with decreased risk is required. OBJECTIVES: We aimed to evaluate the efficacy and safety of low- and high-dose OIT regimens in children with severe milk allergy. METHODS: Overall, 33 participants (median age, 9 years; median final dose of the milk oral food challenge [OFC], 2 mL) were included. The participants were randomly assigned to groups that received either a low (20 mL; n = 19) or high (100 mL; n = 14) maintenance target dose of OIT. The dose was gradually increased to the target dose in the rush escalation phase and was then maintained daily at home. The primary endpoint was the final OFC dose at 6 months of OIT. Adverse events during OIT were evaluated. RESULTS: The final OFC dose after OIT was significantly higher than that before OIT in both groups (low-dose, p = 0.000; high-dose, p = 0.006), but there was no significant difference in the final OFC dose between the 2 groups (p = 0.767). In the maintenance phase, the high-dose group had significantly more severe symptoms than did the low-dose group (0.5%, 11/2,355 total intake events vs. 0.1%, 4/3,230 total intake events; p = 0.018). CONCLUSIONS: An equally increased dose effect was observed for maintenance OIT doses of 20 and 100 mL in children with severe milk allergy. The risk of severe symptoms in the maintenance phase was lower in the low-dose group. A low-dose OIT regimen is recommended for severe milk allergy.

The severity of reaction after food challenges depends on the indication: A prospective multicenter study.

BACKGROUND: There are expanding indications for oral food challenges (OFCs). Although several studies have examined the risk of OFCs, little has been reported on allergic reactions during OFCs depending on the indication. This study assessed the prevalence, severity, and treatment of allergic reactions depending on the indication for OFCs. METHODS: We performed a prospective multicenter study between March 2012 and May 2013. Severity of symptoms elicited by OFCs was classified according to grading of anaphylaxis that ranges from grade 1 (most mild) to grade 5 (most severe). RESULTS: A total of 5062 cases (median age, 3.8 years; males, 65.2%) were analyzed. Allergic reactions were elicited in 2258 (44.6%) OFCs, of which 991 (43.9%) were classified as grade 1, 736 (32.6%) were classified as grade 2, 340 (15.1%) were classified as grade 3, and 191 (8.5%) were classified as grade 4-5. Epinephrine was administered in 7.1% (n = 160) of positive OFCs. Among the top three most common food allergens (hen's egg, cow's milk, and wheat), severity differed significantly depending on the indication for OFC, and adjusted standardized residuals indicated that severity of allergic reactions was higher for the indication to assess threshold level for oral immunotherapy. In addition, the prevalence of epinephrine use was highest for the indication to determine safe intake quantity. CONCLUSIONS: Our study suggested that prevalence, severity, and treatment of allergic reactions differ depending on the indication for OFC. Further studies are needed to determine differences in risks depending on the indication for OFC.

A study on the effect of nutrient intake on the body mass index of mothers of children with food allergies.

BACKGROUND: No previous studies have reported the effect of the presence of children with food allergies (FAs) on the diet and body mass index (BMI) of mothers. Therefore, we conducted a dietary survey and considered nutrients that influenced BMI of mothers. OBJECTIVE: Subjects included 554 mothers-305 mothers of children with FAs (FA mothers; aged 38.4 ± 5.1 years, FA group) and 249 mothers of children without FAs (non-FA mothers; aged 37.7 ± 5.5 years, NFA group). METHODS: We extracted dietary patterns from dietary survey results and investigated the correlation between nutrient intake and BMI. We divided the FA group into two groups (one containing 181 mothers whose children were allergic to ≤ 1 of the three major allergenic foods-eggs, milk and wheat-and another containing 124 mothers whose children were allergic to ≥ 2 of these foods) and conducted a comparative analysis. RESULTS: BMI was significantly lower in the FA group than in the NFA group (20.7 vs. 21.4 kg/m2). There was a significant negative correlation between BMI and vegetable protein intake (ß = -0.196, SE = 0.05). Vegetable protein intake was higher in the group that was allergic to ≥ 2 of the allergenic foods. CONCLUSIONS: BMI of FA mothers is affected by a diet that strictly follows their FA child's allergen-free state-a diet dominated by vegetable protein. These observations suggested that the degree to which an FA mother is affected depends on the number of the three major allergenic foods to which her FA child is allergic.

Effectiveness and Safety of Double-Blind, Placebo-Controlled, Low-Dose Oral Immunotherapy with Low Allergen Egg-Containing Cookies for Severe Hen's Egg Allergy: A Single-Center Analysis.

INTRODUCTION: The usefulness of low-dose oral immunotherapy (OIT) for the treatment of egg allergy has been unclear. OBJECTIVE: To evaluate the efficacy and safety of OIT with low allergen cookies (LACs) containing a low dose of hen's egg. METHOD: Thirty-three patients with severe hen's egg allergy were randomly administered either OIT with LACs (n = 21) or placebo (n = 12). Two patients in the LACs group withdrew before completing OIT. The primary endpoint was the number of good responders (G-R), patients with negative results in the oral food challenge (OFC) with a final dose of 2 g hard-boiled egg whites after 4 months of OIT, in each group. Total OFC Aichi score for anaphylaxis/cumulative protein dose (TS/Pro) as the marker of severity of food allergy was also compared. Adverse events during OIT were evaluated using patients' diaries. RESULTS: The proportion of G-R in the LACs group was higher than in the placebo group (7/19 [37%] vs. 1/12 [8%], χ2 test; p = 0.077). The TS/Pro after OIT in the LACs group was lower than in the placebo group (median score, 44.2 vs. 104.1, p = 0.059; Mann-Whitney U test). The threshold and TS/Pro before and after OIT significantly improved in the LACs group (p = 0.015, p = 0.027, respectively; Wilcoxon signed-rank test). There were 99 recorded incidences of symptoms of 1,938 intake events in the LACs group during OIT. Of these, 90 were mild; no severe symptoms occurred. CONCLUSIONS: OIT with LACs potentially increases the OFC threshold and decreases allergy severity and is a relatively safe treatment modality.

Low-Dose Oral Immunotherapy Using Low-Egg-Allergen Cookies for Severe Egg-Allergic Children Reduces Allergy Severity and Affects Allergen-Specific Antibodies in Serum.

BACKGROUND: We evaluated the safety and efficacy of low-egg-allergen cookies (LAC) as low-dose oral immunotherapy (OIT) in children with severe egg allergy. We also examined the relationship between mild desensitization by low-dose OIT and serum biomarkers of allergy. METHODS: We enrolled 13 children with egg allergy who could not receive OIT with hard-boiled egg white (EW). For 11 participants, OIT was carried out using LAC for 3-4 months. Open food challenges with hard-boiled EW and blood samplings were performed before and after OIT. Participants were divided into 2 groups: high effect (H-E) and no/low effect (N/L-E). Serum levels of total IgE and egg yolk-, EW-, and ovomucoid (OM)-specific IgE, ovalbumin (OVA)- and OM-specific IgG4, IgA1, and IgA2, and the percentage of CD 203c+ were measured. RESULTS: Allergic severity was reduced in 7 patients, who were assigned to the H-E group. Moreover, no study participants were taken off the intake of LAC during OIT. In the H-E group, OVA-specific IgA2 levels after OIT were significantly higher than before OIT. The ratios of OM-specific IgG4/OM-specific IgE and OM-specific IgA2/OM-specific IgE in the H-E group after OIT were significantly higher than before OIT. CONCLUSION: Our findings suggest that low-dose OIT using LAC is an effective and safe treatment for patients with severe egg allergy.

Development and validation of asthma questionnaire for assessing and achieving best control in preschool-age children.

BACKGROUND: Several patient-/caregiver-completed questionnaires have been utilized for the assessment of asthma control. However, due to the diversity in medical/social circumstances, they may not be optimal for use in all countries. The Japanese pediatric asthma guideline (JPGL) aims at higher levels of control compared with other international guidelines, based on a strong social demand for best care. We developed a new control test to help meet that demand. METHODS: A 34-item working questionnaire was developed based on input from pediatric asthma specialists and the caregivers of preschool children with asthma. The questionnaire was administered to caregivers of 565 patients aged <6 years who had physician-diagnosed asthma or ß2-agonist-responsive recurrent wheeze. Then, 6 questions for assessing JPGL-defined control levels were selected from the 34 questions by stepwise logistic regression methods using randomly selected questionnaires completed by two-thirds of the caregivers. We named that set of questions the Best Asthma Control Test for Preschoolers (Best ACT-P). Validation of Best ACT-P was performed using the remaining completed questionnaires. RESULTS: The 6 questions asked about the frequency/severity of cold-induced wheeze, nighttime awakening, exercise-induced symptoms, and disruption of family life due to asthma in the past 4 weeks and hospitalization in the past 12 months. The 6-item logistic model showed good statistical fit, and the scores for the physicians' ratings of the asthma control differed significantly in the hypothetical direction. CONCLUSIONS: Best ACT-P is a valid caregiver-completed questionnaire of asthma control in preschoolers in whom total control needs to be achieved.

THE COMPARISON OF EFFECTIVENESS OF SLOW SPECIFIC ORAL IMMUNOTHERAPY FOR WHEAT ALLERGY USING TWO DIFFERENT INTAKE FREQUENCY.

OBJECTIVE: We performed a constructive study on the effectiveness of oral immunotherapy for wheat allergy using two different intake frequency, and evaluated the impact of intake frequency. SUBJECTS: Of all the subjects who had a positive result in an oral food challenge test for udon (wheat noodles), informed consent was obtained from 49 subjects. Forty-one of the subjects successfully completed testing; data was tabulated for only the 16 in each group who complied with their assigned intake frequency. METHOD: Oral immunotherapy was administered after randomly dividing the subjects into the following two groups according to intake frequency: the frequent group, whose intake was six times/week or more; and the intermittent group, whose intake was two times/week. The ability of these patients to ingest the noodles at the target dose was evaluated after 6 months. RESULTS: After six months, the proportion of subjects who had a negative result on testing with the target dose (20g dried noodle weight for subjects ≤3 years of age, and 50g dried noodle weight for those ≥4 years of age) or who were capable of the target intake within six months was 75%, and there was no difference among the both groups. CONCLUSION: The findings suggest that even when intake frequency is reduced to twice/week, no clear difference is seen with the target dose after six months of immunotherapy.

[The Safety and efficacy of airway-hyperresponsiveness test for asthma using by SK-1211 (Methacholine Chloride)].

BACKGROUND: In abroad, Methacholine Chloride (Provocholine®) is used to meet the indications of the diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma. We examined efficacy, safety and pharmacokinetics of Methacholine Chloride (name of study drug: SK-1211) in order to get approved for the airway hyperresponsiveness test in Japan. METHODS: Fifteen adult healthy volunteers, fifteen adult patients with asthma and ten pediatric patients with asthma were enrolled in this study. The airway hyperresponsiveness test with SK-1211 was conducted in accordance with Japanese Society of Allergology Standard Method. RESULTS: When the threshold value of PC20 was 8 mg/mL, the sensitivity of adult patients with asthma was 66.7% (10/15 subjects) and the specificity of adult healthy volunteers was 86.7% (13/15 subjects). The sensitivity of pediatric patients with asthma was 70.0% (7/10 subjects). Not all subjects experienced some adverse reactions during inhalation of SK-1211, all of which were mild in severity and resolved soon with inhalation of a bronchodilator. There were no serious adverse reactions reported. CONCLUSION: The airway hyperresponsiveness test with SK-1211 was no specific concern with safety and useful in the diagnosis of bronchial airway hyperresponsiveness.

Japanese pediatric guideline for the treatment and management of bronchial asthma 2012.

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a "well-controlled level" for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established.

[Allergy due to probable contamination of bread used for school meals with milk].

BACKGROUND: In May 2012, two schoolchildren developed allergic symptoms after eating a school meal of fried bread in Osaka, Japan. One specific raw material, milk, should not be present in fried bread. However, we suspected the unintentional mixing of milk in the bread manufacturing process. Our aim was to verify the reason if this was so. METHODS: We first manufactured bread that contained milk as one of its components. We then thoroughly cleaned the manufacturing line except for the dough divider and, as per the revised instruction manual, continuously manufactured bread that did not contain milk. In this manner, we tried to simulate the conditions at the time of the incident. Casein is a major milk protein. We, therefore, determined casein concentration in the milk-free bread, using casein enzyme-linked immunosorbent assay. RESULTS: We observed casein levels higher than 1000 ppm in the initial lots of breads, but lower levels in the later lots. Casein levels also decreased upon frying of bread. CONCLUSION: High casein levels, which were observed in the earlier lots of breads, were lower in the later lots. In the manufacturing line, the remnants of the bread dough that contained milk presumably got mixed with the dough used in the subsequent manufacture of milk-free bread.

Suppressed pediatric asthma hospitalizations during the COVID-19 pandemic in Japan, from a national survey.

BACKGROUND: Acute asthma exacerbation in children is often caused by respiratory infections. In this study, a coordinated national surveillance system for acute asthma hospitalizations and causative respiratory infections was established. We herein report recent trends in pediatric acute asthma hospitalizations since the COVID-19 pandemic in Japan. METHODS: Thirty-three sentinel hospitals in Japan registered all of their hospitalized pediatric asthma patients and their causal pathogens. The changes in acute asthma hospitalization in children before and after the onset of the COVID-19 pandemic and whether or not COVID-19 caused acute asthma exacerbation were investigated. RESULTS: From fiscal years 2010-2019, the median number of acute asthma hospitalizations per year was 3524 (2462-4570), but in fiscal years 2020, 2021, and 2022, the numbers were 820, 1,001, and 1,026, respectively (the fiscal year in Japan is April to March). This decrease was observed in all age groups with the exception of the 3- to 6-year group. SARS-CoV-2 was evaluated in 2094 patients from fiscal years 2020-2022, but the first positive case was not detected until February 2022. Since then, only 36 of them have been identified with SARS-CoV-2, none of which required mechanical ventilation. Influenza, RS virus, and human metapneumovirus infections also decreased in FY 2020. In contrast, 24% of patients had not been receiving long-term control medications before admission despite the severity of bronchial asthma. CONCLUSION: SARS-CoV-2 was hardly detected in children with acute asthma hospitalization during the COVID-19 pandemic. This result indicated that SARS-CoV-2 did not induce acute asthma exacerbation in children. Rather, infection control measures implemented against the pandemic may have consequently reduced other respiratory virus infections and thus acute asthma hospitalizations during this period. However, the fact that many hospitalized patients have not been receiving appropriate long-term control medications is a major problem that should be addressed.

Parents' Fears about Hospital Visits and Trait Anxiety in the COVID-19 Pandemic.

Anxiety in parents of children with allergic diseases during the COVID-19 pandemic may impact hospital visits. This study explored the effect of the pandemic on parents' fears about hospital visits and their relationship with their personality traits. A cross-sectional, questionnaire-based study was conducted between September 2020 and March 2021, with parents of children aged 0-15 years, who regularly visited 24 outpatient facilities for allergic disease. The survey included patient information, fears about hospital visits, desired information, and the State-Trait Anxiety Inventory. Responses were compared between parents with high and low trait anxiety. The response rate was 97.6% (2439/2500). The most common fear was "Fear of getting medical care as usual (85.2%)" and "Fear of COVID-19 infection during hospital visits (87.1%)". High trait anxiety showed a significant association with "Fear of worsening of children's allergies" (adjusted OR: 1.31, 95%CI: 1.04 to 1.65, p = 0.022), and "Fear of worsening of COVID-19 due to allergy" (adjusted OR: 1.52, 95%CI: 1.27 to 1.80, p < 0.01). Healthcare professionals should share updates on COVID-19 and healthcare system to reduce parents' fear. Subsequently, they should communicate the importance of continuing treatment to prevent worsening of COVID-19 and avoid emergency visits, considering parental trait anxiety.