Epidemiology of anaphylaxis and biphasic reaction in Japanese children.

AIM: Anaphylaxis is common, but can sometimes be fatal. However, data on the epidemiology and characteristics of anaphylaxis are limited. Although 0.9%-14.7% of anaphylactic reactions in children are biphasic, it is unclear what the characteristics of biphasic reaction are and how long patients with this reaction should be observed. The present study aimed to investigate the epidemiology of anaphylaxis and biphasic reactions and identify the characteristics of the latter. METHODS: We conducted an observational study of patients who visited the pediatric emergency department (PED) and were hospitalized for anaphylaxis between March 2010 and March 2017. RESULTS: Of the 264,689 children who visited our PED, 353 (1.3 per 1,000 patient) were hospitalized for anaphylaxis, and six (1.7%) had a biphasic reaction. Of the patients with a biphasic reaction, the median time from initial anaphylaxis to the biphasic reaction was 5.9 (interquartile range [IQR] = 3.3-7.6) hours. Symptoms of the initial episode and the biphasic reaction varied. One (0.3%) of the 353 patients developed a clinically important biphasic reaction that required epinephrine administration. CONCLUSIONS: The rate of biphasic reactions was 1.7%, and that of clinically important biphasic reactions was 0.3%. Patients with anaphylaxis need to be carefully monitored because of the regular occurrence of biphasic reactions.

The prevalence of oral symptoms caused by Rosaceae fruits and soybean consumption in children; a Japanese population-based survey.

BACKGROUND: Pollen food Syndrome (PFS) to Rosaceae fruits and soybean, related to Bet v 1 homologue sensitization has been reported increasingly throughout Japan, possibly due to the wide distribution of alder. METHODS: In 2015, we conducted a school-based questionnaire survey among two age groups; students in primary school (Years 1-2) and secondary school (Years 8-9) from each of the 47 prefectures of Japan. We analyzed the prevalence, demographic and clinical characteristics of children with oral symptoms to Rosaceae fruits/soybean; defined as oral symptoms occurring shortly after ingesting apple, peach, cherry or soybean. Additionally, we assessed the correlation between the prevalence and external data on alder sensitization rates by prefecture. RESULTS: Responses from 41,264 primary and 35,302 secondary school students were analyzed. The prevalence of oral symptoms to Rosaceae fruits/soybean was 0.99%, 95%CI: 0.89-1.09% and 2.75%, 95%CI: 2.59-2.93% among each age group, respectively. Children with oral symptoms were more likely to have parental and personal history of allergic disease compared to those without symptoms. Oral symptoms were experienced more often in children with severe spring allergic rhinitis or have both allergic rhinitis and wheeze. There was a strong correlation between the prevalence of oral symptoms and alder sensitization rates by prefecture among both age groups (r = 0.63, p < 0.001 and r = 0.76, p < 0.001, respectively). CONCLUSIONS: Oral symptoms to Rosaceae fruits/soybean, which is suggestive of PFS was reported by 1-3% Japanese school children. It was associated with the geographic alder sensitization rate, supporting the underlying sensitization to Bet v 1.

Metered-dose inhaler ipratropium bromide for children with acute asthma exacerbation: A prospective, non-randomized, observational study.

BACKGROUND: Ipratropium bromide (IB), when administered with ß2-agonists, is effective in reducing hospital admissions of children presenting to the emergency department (ED) with severe asthma. While IB is commonly delivered in its nebulized form, using a metered-dose inhaler (MDI), can, reportedly, shorten patients' length of stay in the ED. However, the effectiveness and safety of IB administration using an MDI with a spacer have not been established. This study aimed to investigate the effectiveness and safety of MDI-delivered IB in pediatric patients with acute asthma exacerbation. METHODS: This prospective, non-randomized, observational study included patients aged ≥4 years with a history of severe asthma exacerbation. Patients received IB via MDI with a spacer three times at 20-min intervals. IB use was determined by the physicians' treatment policy. Propensity score matching was used to adjust the confounding factors related to IB administration. RESULTS: Of the 158 patients, 88 were treated with IB and 70 were treated without IB. A propensity score-matching analysis extracted 54 patients from each group. We found no statistical difference in the admission rate of the two groups (IB group: 25.9% vs non-IB group: 31.5%; P = 0.67). The post-treatment modified pulmonary index scores (mean ± SD) were also similar (IB: 6.6 ± 2.0 vs non-IB: 6.3 ± 2.5; P = 0.53). Only one patient (1.0%) treated with IB experienced vomiting, which resolved spontaneously. CONCLUSION: The metered-dose inhaler IB was ineffective in reducing the admission rate possibly because it was less effective than a nebulizer for IB inhalation.

Changes in the characteristics of patients with latex allergy from 1999 to 2014.

OBJECTIVES: We conducted a multicenter study using the same questionnaire in 1999 and 2014 to investigate changes in the characteristics of patients with latex allergy. METHODS: We mailed questionnaires on latex allergy to hospitals in Japan that were members of the Japanese Latex Allergy Society. RESULTS: We compared the 25 responses received in 2014 and the 81 responses received in 1999. With regard to the age distribution, the number of patients with latex allergy in their 20s declined significantly from 1999 to 2014 (P=0.004). The largest proportion of latex allergy cases was observed among those aged <10 years. The incidence of cases caused by medical rubber gloves decreased significantly (P=0.004). Moreover, latex-fruit syndrome increased from 15% to 40% (P=0.006). CONCLUSIONS: Our findings indicate that the frequency of occurrence of latex allergy in people in their 20s decreased from 1999 to 2014. The largest proportion of latex allergy cases was observed among those aged <10 years. Future measures to protect children are required.

Nationwide survey of the prevalence of wheeze, rhino-conjunctivitis, and eczema among Japanese children in 2015.

BACKGROUND: Global surveys and cohort studies have been conducted to evaluate the prevalence of allergic disease in childhood, but only a few nationwide surveys have been conducted in Japan. We aimed to report the prevalence of childhood allergic disease in Japan and determine the prevalence distribution by sex and prefecture. METHODS: In 2015, we conducted a school-based questionnaire survey using the Japanese version of the International Study of Asthma and Allergies in Childhood questionnaire among two age groups: primary school students (PS, 6-8 years old) and middle school students (MS, 13-15 years old). The schools were randomly selected from each prefecture. RESULTS: Valid responses were obtained from 42,582 PS and 36,638 MS. Among PS and MS, the prevalence of wheeze was 10.2% and 8.2%, that of allergic rhino-conjunctivitis was 18.7% and 26.7%, and that of eczema was 14.6% and 9.7%, respectively. In terms of sex, the prevalence of wheeze and rhino-conjunctivitis was higher in male PS while that of rhino-conjunctivitis and eczema was higher in female MS. In terms of prefecture, there was a two-fold difference in the prevalence of wheeze and eczema and a four-fold difference in the prevalence of rhino-conjunctivitis, with each disease showing different distribution patterns. CONCLUSIONS: We demonstrated the prevalence of allergic disease among PS and MS in 2015. The prevalence tended to be higher in male PS and female MS. Each disease exhibited different prevalence ranges and distributions. Identifying the factors behind these differences is a topic for future research.

An independent relation of atopic dermatitis to exercise-induced wheezing in asthmatic children.

BACKGROUND: Atopic dermatitis (AD) and exercise-induced asthma (EIA) are common in asthmatic children, and exercise is the most common trigger other than infection for acute onset asthma attack in children. We examined whether AD is related to exercise-induced wheezing (EIW), some proxy for EIA. METHODS: Japanese version of the International Study of Asthma and Allergies in Childhood questionnaires were used. For 12,405 asthmatic school children, AD was defined as itchy rash coming and going for at least 6 months at any time in the last 12 months with affecting places of flexural parts of body, and severity of AD was rated according to frequency of being kept awake at night with the itch as follows: never in the past 12 months, less than one night per week and one or more nights per week. RESULTS: Adjusted for frequency of asthma attack, odds ratios (OR) of children with current AD as compared to those without AD for having EIW were 1.32 (95% confidence interval = 1.15-1.52), 1.35 (1.14-1.68) and 1.10 (0.92-1.31) for primary school, junior high school and high school children, respectively. EIW was more likely observed in accordance with increasing severity of AD in the primary school children with ORs of 1.12, 1.59 and 1.54 (p for trend < 0.01), and in the junior high school ones with ORs of 1.18, 1.31, 2.03 (<0.01), respectively. CONCLUSIONS: AD may be possibly related to EIW. Further studies investigating effect of AD treatment on EIW may be required.

Fentanyl-associated anaphylaxis in an infant with tetralogy of Fallot: a case report.

BACKGROUND: Anaphylactic reactions to opioids are rare. We report a case of an infant who experienced fentanyl-induced anaphylaxis. CASE PRESENTATION: A 2-month-old male was scheduled to undergo a Blalock-Taussig shunt. Following uneventful anesthetic induction, he experienced profound hypotension and generalized erythema. Anaphylaxis was clinically diagnosed, and he was treated with epinephrine, vasopressin, and fluids. The surgery was canceled, and he was transferred to the intensive care unit after restoration of his hemodynamic status. Intradermal testing was performed for all of the drugs given during the anaphylactic event on postoperative day (POD) 3. The results showed a positive reaction to fentanyl. For the second anesthesia scheduled on POD 5, morphine sulfate was selected as an alternative opioid. Anesthesia was maintained uneventfully with sevoflurane, morphine, and rocuronium. CONCLUSION: Intradermal testing revealed fentanyl anaphylaxis. We were able to manage the patient by using of morphine as an alternative opioid for the subsequent anesthesia.

[THE COURSE OF ASTHMA SYMPTOMS IN JAPANESE CHILDREN; THE FIRST REPORT FROM A MULTICENTER PROSPECTIVE COHORT STUDY].

BACKGROUND: The use of asthma control guidelines and anti-inflammatory drugs have significantly decreased the number of severe asthma cases including death from asthma. However, there are few prospective cohort studies among pediatric asthma patients in Japan describing the course of asthma symptoms with the treatment taken into consideration. METHOD: We recruited a total of 851 children diagnosed with asthma through 90 hospitals and clinics in 2004 to 2006. Questionnaires were posted annually to collect data on their asthma symptoms, treatment and environmental exposures. We analyzed the disease course in the first 5 years among the children who were registered at age 4 or younger. RESULTS: The disease course of a total of 641 children, aged 2.8+/-1.1 (mean+/-SD) at registration were analyzed. The proportion of children who had intermittent symptoms increased from 37.6% at registration to 86.5% at 5 years, and the proportion of children with intermittent severity increased from 7.0% to 38.9%, showing a significant decrease in the overall severity. The proportion of children using ß2 stimulants decreased from 87.8% at registration to 53.5% at 5 years, while the use of inhaled cortico-steroids were 41.6% at registration and 38.1% at 5 years. CONCLUSION: Most of the children with pre-school onset asthma had their symptoms controlled, and had decreased severity over 5 years.

Hand eczema as a risk factor for food allergy among occupational kitchen workers.

BACKGROUND: An increasing number of studies in children is highlighting the importance of transdermal routes of exposure to food allergens through damaged skin in the pathogenesis of food allergies. However, data on this in adults are limited. A few case-series studies has documented development of food allergy among kitchen workers with hand eczema after direct contact exposure to foods. METHODS: To explore the significance of hand eczema as a risk factor for food allergies in adults at the epidemiological level, we performed a cross-sectional web-based questionnaire survey on kitchen workers whose exposures were classed as occupational (cooks and food handlers, n = 1592) or non-occupational (housewives, n = 1915). Logistic regression was used to explore the association between the presence/severity of hand eczema and the risk of food allergy after adjustment for potential confounders. RESULTS: Current hand eczema and current diagnosed food allergy were more common among occupational kitchen workers (OKW) than among non-occupational kitchen workers (NOKW) (32.3%-vs-29.9% and 9.9%-vs-3.8%, respectively). Current hand eczema was significantly associated with increased risk of current diagnosed food allergy in OKW (adjusted odds ratio 2.4, 95% CI 1.6-3.7). Those with more severe hand eczema were more likely to suffer from allergic symptoms for foods, and diagnosed food allergy. CONCLUSIONS: This study illustrates a significant public health problem in the adult population, documenting a major impact of hand eczema on the ongoing adult food allergy epidemic.

Childhood asthma control in Japan: A nationwide, cross-sectional, web-based survey.

BACKGROUND: Recent surveys have shown that many patients with asthma experience uncontrolled symptoms and decreased quality of life due to their disease. However, few large population-based studies have evaluated asthma control in Japanese children. OBJECTIVE: To show the reality of asthma control and the pattern of asthma controller medication use among Japanese children. METHODS: In 2012, a web-based survey was conducted to identify children aged 6 to 11 years with asthma in Japan. Among children with current asthma, we collected information regarding their asthma controller medication use and evaluated the control level of asthma using the Childhood Asthma Control Test (C-ACT). In this study, a C-ACT score of 19 or less, 20 to 22 and over 22 were classified as uncontrolled asthma, well-controlled asthma, and optimally controlled asthma, respectively. RESULTS: Among the 3,033 children with current asthma, 442 (14.6%), 635 (20.9%), and 1,956 (64.5%) children had uncontrolled, well-controlled, and optimally controlled disease, respectively. In the past 1 month, 1,387 (45.7%) reported receiving at least 1 asthma controller medication with 638 (21.0%) reported receiving inhaled corticosteroid. Among the children with uncontrolled asthma, 67 (15.2%) were not receiving any asthma controller mediations. Among children receiving asthma controller medication, 27.0%, 31.4% and 41.5% had uncontrolled, well-controlled, and optimally controlled asthma, respectively. CONCLUSIONS: Although more than half of children with current asthma had optimally controlled disease, some children without any controller medications and more than a quarter of the children receiving asthma controller medications had uncontrolled disease.

IPRATROPIUM BROMIDE FOR ACUTE ASTHMA IN CHILDREN: A RETROSPECTIVE TRIAL.

BACKGROUND: Inhaled anticholinergics such as ipratropium bromide (IB), when administered with ß2-agonists, are effective in reducing hospital admissions of children presenting to the emergency department with moderate to severe asthma. However, treatment of acute asthma with IB is still uncommon in Japan. The aim of this study was to investigate the effectiveness and safety of IB for the treatment of pediatric acute asthma. METHODS: We conducted a retrospective study to compare the admission rate of patients who received IB with those who did not. Patients aged 4 years or older with a history of moderate to severe attacks were included. For analysis, propensity score matching was used to adjust the confounding factors related to IB use. Patients received IB by metered-dose inhaler (40µg per dose) with a spacer three times at 20-min intervals. RESULTS: Among 175 patients included in the analysis, 102 patients were treated with IB (IB group) and 73 patients were treated without IB (Non-IB group). A propensity score matching analysis extracted 63 patients from each group. There was no statistical difference between the two groups in terms of admission rate (IB group 12.7% vs Non-IB group 9.5%; p=0.78). One patient (1.0%) treated with IB experienced dryness of the mouth, which resolved spontaneously. CONCLUSIONS: The admission rate did not decline with IB use. Several confounding factors could have influenced and limited our results. A prospective study is needed to investigate the effectiveness of IB in Japan.

Accurate Determination of Childhood Food Allergy Prevalence and Correction of Unnecessary Avoidance.

PURPOSE: Because the true prevalence of food allergy (FA), as based on the results of an oral food challenge test (OFC), is unknown, it is likely that children with suspected FA unnecessarily eliminate potentially causative foods. This study aimed to identify the prevalence of FA and to determine the proportion of children who unnecessarily eliminate food. METHODS: To identify children with FA, a primary survey was conducted via a questionnaire with all children aged 0-18 years in Niijima village (remote islands of Japan). In the secondary survey, a detailed medical interview was conducted by doctors with children who currently did not eat some foods. The third survey involved serum food-specific immunoglobulin E (IgE) tests and an OFC for children with suspected FA. RESULTS: Of 376 enrolled children, 374 (99.5%) completed the questionnaire. Some foods were eliminated by 18.6% and 13.0% of all children and those ≥6 years old, respectively. The target population for the secondary survey included 69 children who all completed the medical interview. The target population for the third survey consisted of 35 children, of whom 26 (74.3%) underwent the blood test. An OFC was performed 35 times with 20 children. As a result, the prevalence of FA was 4.9% in children of all ages and 4.7% in those ≥6 years old. Moreover, 55.0% children were able to cease eliminating food intake. CONCLUSIONS: It is possible that a considerable number of children unnecessarily eliminate food because of suspected FA.

Long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with severe uncontrolled asthma.

BACKGROUND: Omalizumab is effective and well-tolerated in children with moderate to severe allergic asthma. However, the effects of long-term treatment with omalizumab in this population haven't been well investigated. The objective of this study is to evaluate the long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab in children with uncontrolled severe asthma. METHODS: Thirty-eight Japanese children (aged 7-16 years) who completed the 24-week treatment core study were included in an uncontrolled extension study, in which treatment with omalizumab continued until the pediatric indication was approved in Japan (ClinicalTrials.gov number: NCT01328886). RESULTS: Thirty-five patients (92.1%) completed the extension study. The median exposure throughout the core and extension studies was 116.6 weeks (range, 46.9-151.1 weeks). The most common adverse events were nasopharyngitis, influenza, upper respiratory tract infection, and asthma. Serious adverse events developed in 10 patients (26.3%), but resolved completely with additional treatments. Incidence of adverse events didn't increase with extended exposure with omalizumab. Twenty-nine patients (76.3%) achieved completely- or well-controlled asthma compared with 9 patients (23.7%) at the start of the extension study. QOL scores, the rates (per year) of hospitalizations and ER visits were significantly improved compared with the baseline of the core study [39.0 vs 48.0 (median), p < 0.001 for QOL, 1.33 vs 0.16, p < 0.001 for hospitalization, 0.68 vs 0.15, p = 0.002 for ER visits]. Remarkably, the mean total IgE level showed a decreasing trend while exposure to omalizumab remained at steady-state. CONCLUSIONS: Long-term treatment with omalizumab is well-tolerated and effective in children with uncontrolled severe allergic asthma. No new safety findings were identified.

Randomized controlled trial of oral immunotherapy for egg allergy in Japanese patients.

BACKGROUND: Egg allergy is one of the most common food allergies in young children. While oral immunotherapy (OIT) is not routinely recommended in current guidelines, it has been considered as a potential alternative treatment strategy. Studies on OIT for food allergy have been explored, but no controlled trials have been reported in Japan. METHODS: The first oral food challenge (OFC) was performed before treatment to ensure diagnosis and evaluate the threshold dose for egg using the double-blind, placebo-controlled food challenge. Participants were randomly assigned by computerized algorithm to receive OIT using egg (OIT group) or no egg (egg elimination [EE] group). A second OFC was performed in both groups approximately 6 months after therapy. Blood samples were collected and egg white-specific immunoglobulin (Ig)E and IgG4 were measured before and after the treatment period. RESULTS: Eight of the 14 patients (57%) in the OIT group had no allergic reaction to 4 g dry egg powder whereas none of the 16 patients in the EE group did. All 14 patients in the OIT group had increased threshold for egg powder in the second OFC compared with baseline. There was no significant change in egg white-specific IgE level during therapy. After therapy, egg white-specific IgG4 increased significantly in the OIT group, but not in the EE group. CONCLUSION: OIT is effective in increasing the threshold for allergens and inducing desensitization in Japanese egg allergy patients, similarly to North American and European patients.

Environmental factors associated with childhood eczema: Findings from a national web-based survey.

BACKGROUND: Genetic and environmental factors are known to be related to the development of childhood eczema. Our aim was to assess the environmental factors associated with the prevalence of eczema among children using a web-based survey. METHODS: In June 2012, we conducted a nation-wide web-based survey to identify the prevalence and characteristics of allergic diseases among Japanese children. The prevalence of allergic diseases including eczema was assessed using the International Study of Asthma and Allergies in Childhood core questionnaire. The associations between eczema prevalence and environmental factors, as well as those between background characteristics and comorbid allergic diseases among 6-12 year old children were assessed. RESULTS: A total of 28,348 children were included in the analysis. The prevalence of current eczema was 13.0%. Current eczema was significantly associated with a higher prevalence of wheeze, rhinitis, and food allergy. In multiple logistic regression models, birth during autumn (aOR: 1.18 95%CI: 1.06-1.31) or winter (aOR: 1.21 95%CI: 1.08-1.34), duration of exclusive breastfeeding for at least 6 months (aOR: 1.14 95%CI: 1.06-1.23), and ownership of a pet from infancy (aOR: 2.61 95%CI: 1.68-4.07) were also associated with a higher prevalence of eczema. The prevalence was lower in those with a high annual household income (aOR: 0.90 95%CI: 0.81-0.99) and 2 or more siblings (aOR: 0.86 95%CI: 0.76-0.97). CONCLUSIONS: Duration of breastfeeding, season of birth, pet ownership, household income, and the number of siblings were associated with the prevalence of childhood eczema in a nationwide web survey.