Nocturnal Scratching and Quality of Sleep in Children with Atopic Dermatitis.

Itching due to atopic dermatitis causes sleep disorders in children, but its pathology is unknown. The aim of this study is to investigate nocturnal scratching as an indirect index of itching during sleep and its relationship with depth of sleep in children with atopic dermatitis. Nocturnal scratching was measured in a total of 20 children with atopic dermatitis, using a smartwatch installed with the application Itch Tracker. Depth of sleep was analysed using polysomnography. The severity of atopic dermatitis was scored using Eczema Area and Severity Index (EASI) and Patient-Oriented Eczema Measure (POEM). The number and time of nocturnal scratching measured by Itch Tracker had a significantly positive correlation with EASI scores, whereas POEM scores were not correlated with EASI scores. Mean sleep efficiency was 90.0% and scratching episodes (n = 67) started mainly during the awake stage or light sleep stages. In the scratching episodes that started during sleep stages (n = 34), the sleep stage changed to a lighter one or to the awake stage in 35.5% of episodes. Itch Tracker is applicable to measure nocturnal scratching in children. Nocturnal scratching can deteriorate quality of sleep by changing the sleep stage to a lighter one or to the awake stage.

Efficacy and safety of tezepelumab in patients recruited in Japan who participated in the phase 3 NAVIGATOR study.

BACKGROUND: Tezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced exacerbations by 56% compared with placebo in adults and adolescents with severe, uncontrolled asthma. This analysis evaluated the efficacy and safety of tezepelumab in NAVIGATOR patients recruited in Japan. METHODS: NAVIGATOR was a phase 3, multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Endpoints assessed included: the annualized asthma exacerbation rate (AAER) over 52 weeks (primary endpoint) and the change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV1) and Asthma Control Questionnaire (ACQ)-6 score. The safety of tezepelumab was also assessed. RESULTS: Overall, 97 patients recruited in Japan were randomized (tezepelumab, n = 58; placebo, n = 39). The AAER over 52 weeks was 1.54 (95% confidence interval [CI]: 0.90, 2.64) with tezepelumab compared with 3.12 (95% CI: 1.82, 5.35) with placebo (rate ratio: 0.49 [95% CI: 0.25, 0.99]; 51% reduction). For tezepelumab and placebo, the least-squares mean (standard error) change from baseline to week 52 for pre-bronchodilator FEV1 was 0.23 (0.06) L and 0.19 (0.07) L and the ACQ-6 score was -1.12 (0.15) and -0.97 (0.19), respectively. The frequency of adverse events was similar between treatment groups (tezepelumab, 86.2%; placebo, 87.2%). CONCLUSIONS: Tezepelumab reduced exacerbations compared with placebo, and was well tolerated, in NAVIGATOR patients with severe, uncontrolled asthma recruited in Japan.

Effect of age on exercise-induced bronchoconstriction in children and adolescents with asthma.

OBJECTIVE: The relationship between exercise-induced bronchoconstriction (EIB) and exertional dyspnea in children and adolescents is yet to be fully established. This study examined whether indicators of fractional exhaled nitric oxide (FeNO), forced expiratory volume in 1 s (FEV1) percent predicted at baseline, and dyspnea are useful for predicting children and adolescents with EIB. METHODS: We enrolled 184 children and adolescents diagnosed with asthma (mean age 11.2 years); participants were divided into two groups according to age (12 years) and were subjected to a 6-min exercise challenge test. Lung function tests and modified Borg scale scores were used to examine perceptions of dyspnea at 0, 5 and 15 min after exercise. RESULTS: Among children, the maximum percentage drop in FEV1 after exercise correlated significantly with FeNO (adjusted ß = 2.3, P < 0.001) and with the perception of dyspnea at 5 min after exercise (adjusted ß = 1.9, P < 0.001). Among adolescents, the maximum percentage drop in FEV1 correlated with FeNO (adjusted ß = 2.7, P = 0.007) and with lung function (FEV1, percent predicted; adjusted ß = -0.28, P = 0.006). Children with EIB had significantly stronger dyspnea after exercise than did children without EIB. Adolescents even without EIB may experience more exertional dyspnea than children without EIB. CONCLUSIONS: Overall, our findings indicated that EIB was associated with FeNO and exertional dyspnea in asthmatic children. By contrast, EIB was associated with FEV1 percent predicted at baseline and FeNO but not with exertional dyspnea in asthmatic adolescents.

Roles of omalizumab in various allergic diseases.

IgE and mast cells play a pivotal role in various allergic diseases, including asthma, allergic rhinitis, and urticaria. Treatment with omalizumab, a monoclonal anti-IgE antibody, has significantly improved control of these allergic diseases and introduced a new era for the management of severe allergic conditions. About 10 years of experience with omalizumab treatment for severe allergic asthma confirmed its effectiveness and safety, reducing symptoms, frequency of reliever use, and severe exacerbations in patients with intractable conditions. Omalizumab is particularly useful in childhood asthma, where atopic conditions often determine clinical courses of asthma. Recently, omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) with the fixed dose of 300 mg. Although the mechanisms underlying the actions of omalizumab in CSU are not fully clarified, nearly 90% of patients with CSU showed a complete or a partial response to omalizumab treatment. Furthermore, omalizumab is just approved for the treatment of severe Japanese cedar pollinosis (JC) based on the successful results of an add-on study of omalizumab for inadequately controlled severe pollinosis despite antihistamines and nasal corticosteroids. For proper use of omalizumab to treat severe JC, co-administration of antihistamines is necessary, while patients should meet the criteria including strong sensitization to Japanese cedar pollen (≥class 3) and poor control under standard treatment. In the management of severe allergic diseases using omalizumab, issues including cost and concerns about relapse after its discontinuation should be overcome. At the same time, possibilities for application to other intractable allergic diseases should be considered.

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.

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.

Association between Asian dust exposure and respiratory function in children with bronchial asthma in Nagasaki Prefecture, Japan.

BACKGROUND: Studies on the adverse effects of Asian dust (AD) on respiratory function in children are scarce. The objective of this study was to examine the association between AD and respiratory function by measuring peak expiratory flow rates (PEFRs) in asthmatic children. METHODS: The study was carried out from March to May from 2014 through 2016. One hundred ten children with bronchial asthma were recruited from four hospitals in the Goto Islands and south Nagasaki area in Nagasaki prefecture. The parents were asked to record their children's PEFRs every morning/evening and clinical symptoms in an asthma diary. AD was assessed from light detection and ranging data, and a linear mixed-effects model was used to estimate the effects of AD on daily PEFR. Time-stratified case-crossover analyses were performed to examine the association between AD and asthma attacks defined by reduction levels in PEFR. RESULTS: AD was detected on 11 days in the Goto Islands, and on 23 days in the south Nagasaki area. After adjusting for age, sex, temperature, and daily oxidants, we found a consistent association between AD and a 1.1% to 1.7% decrease in PEFR in the mornings and a 0.7% to 1.3% decrease in the evenings at a lag of 0 to 5 days. AD was not associated with the number of asthma attacks, respiratory symptoms, or other symptoms at any lag days examined. CONCLUSIONS: Exposure to AD was associated with reduced PEFR, although the effects were not large enough to induce clinically apparent symptoms, in clinically well-controlled asthmatic children.

[EVALUATION OF ADRENAL CORTICAL FUNCTION USING SALIVARY CORTISOL MEASUREMENTS IN CHILDREN WITH BRONCHIAL ASTHMA].

BACKGROUND: When corticosteroids are used for a long time in patients with bronchial asthma, a decrease in adrenal cortex function occurs. We investigated the use of salivary cortisol measurements as a simple, noninvasive method for the evaluation of the adrenal cortex function in pediatric asthmatic patients. METHODS: Plasma and salivary cortisol levels were measured from 8:00 am to 10:00 am in 248 pediatric asthmatic patients aged 0-18 years that were under long-term care management at the National Hospital Organization Fukuoka National Hospital in 2011-2013. We determined the correlation between plasma and salivary cortisol levels and calculated a salivary cortisol cut-off value for screening adrenocortical function. RESULTS: There was a significant positive correlation between salivary cortisol levels and plasma cortisol levels in all patients, patients under age 3, and patients over age 3 (r=0.759, r=0.563, r=0.827, respectively). Salivary cortisol cut-off values were 0.015µg/dL for plasma cortisol levels below 3µg/dL (sensitivity 83%, specificity 82%), and 0.045µg/dL those below 5µg/dL (sensitivity 83%, specificity 75%). 5µg/dL or less is an abnormal value, and 3µg/dL or less is considered to be adrenal insufficiency. CONCLUSION: Salivary cortisol levels were positively correlated with plasma cortisol levels in pediatric asthmatic patients. This is a useful method for frequently monitoring young children with adrenal dysfunction or severe asthma that are treated with high doses of inhaled corticosteroids.

[THREE CASES OF ATOPIC DERMATITIS CHILDREN WITH INTRACTABLE PRURIGO NODULARIS].

BACKGROUND: Prurigo nodularis is a chronic disease characterized by a hard dome-like or wart-like nodule which is solitary and does not fuse. Prurigo nodularis presents as one of the symptoms of atopic Dermatitis (AD). CASES: We present three cases of AD children with intractable prurigo nodularis. 1) a 9-Year-Old Boy, 2) an 11-Year-Old Girl, and 3) an 8-Year-Old Boy. The Eczema Area and Severity Index (EASI) in the first visit was 27.7, 30.6, and 49.0, respectively. All patients had been treated with very strong or strongest potency topical steroids for 3-9 years. Quality of life (QOL) had declined due to severe pruritus, and they had striae and secondary adrenal suppression as side effects of steroids. Case 1 and 2 were treated with Cyclosporine A (CyA), case 3 was treated with Duplimab when he was 15 years old; all patients improved. DISCUSSION: CyA and Duplimab are not indicated for children in Japan, however, it is necessary to consider not only topical medicine but also other additional treatments when faced with adrenal suppression as a side effect of steroids or loss of QOL. CONCLUSION: CyA and Duplimab, that were effective in AD with intractable prurigo nodularis, are expected to become indications for AD children.

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.

Association between daily ambient air pollution and respiratory symptoms in children with asthma and healthy children in western Japan.

OBJECTIVE: In recent years, air pollutant concentrations in Japan have decreased slightly; however, there are growing concerns about the influences of transnational air pollution on respiratory illness. We aimed to clarify the short-term association between the ambient air pollution and respiratory symptoms among children without asthma, children with asthma not using long-term medications (CA-nonLTM), and those using them (CA-LTM). METHODS: A total of 138 children attending 2 primary schools and 71 children with asthma regularly visiting cooperating medical institutions were recruited. Study participants measured peak expiratory flow (PEF) twice a day and recorded coughing, nasal symptoms, and medication use in a diary. Predicted associations between daily air pollutant concentrations and respiratory symptoms, and PEF were evaluated using case-crossover and generalized estimate equation models. RESULTS: Changes in %maxPEF per 10 ppb oxidant (Ox) increase in children without asthma, CA-nonLTM, and CA-LTM were -0.26% (95% CI: -0.49, -0.03), -0.51% (95% CI: -0.89, -0.12), and -0.20% (95% CI: -0.42, 0.01), respectively. The odds ratios for coughing per 10 ppb Ox increase in the Lag0 model were 1.34 (95% CI: 1.11, 1.60), 1.52 (95% CI: 1.12, 2.07), and 1.06 (95% CI: 0.93, 1.20), respectively. These suggested that the Ox concentration has graded effects on %maxPEF and coughing, in the following descending order, CA-nonLTM, children without asthma, and CA-LTM. The Ox concentration was also positively associated with nasal symptoms in children without asthma and CA-LTM. CONCLUSION: Our results suggest that using long-term medications to manage asthma may play an important role in preventing exacerbation of respiratory symptoms due to air pollution.

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.

Long-term safety of subcutaneous immunotherapy with TO-204 in Japanese patients with house dust mite-induced allergic rhinitis and allergic bronchial asthma: Multicenter, open label clinical trial.

BACKGROUND: To evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial. METHODS: Japanese patients aged 5-65 years were eligible for the study, if they had HDM-induced allergic rhinitis (AR), allergic bronchial asthma (BA), or both. TO-204 was administered in a dose titration scheme, and the maintenance dose was determined according to the predefined criteria. The treatment period was 52 weeks, and patients who were willing to continue the treatment received TO-204 beyond 52 weeks. This clinical trial is registered at the Japan Pharmaceutical Information Center (Japic CTI-121900). RESULTS: Between July 2012 and May 2015, 44 patients (28 with AR and 16 with allergic BA) were enrolled into the study. All patients were included in the analysis. The duration of treatment ranged from 23 to 142 weeks and the median maintenance dose was 200 Japanese allergy units (JAU). Adverse events occurred in 22 patients (50%). The most common adverse event was local reactions related to the injection sites. Four patients experienced anaphylactic reactions when they were treated with the dose of 500 JAU. Two patients experienced anaphylactic shock with the doses of 1000 JAU at onset. These 6 patients could continue the study with dose reduction. CONCLUSIONS: Safety profile of TO-204 was acceptable in Japanese patients with HDM-induced AR or allergic BA. Higher doses should be administered carefully, because the risk of anaphylaxis increased at doses of 500 or 1000 JAU.

[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.

Efficacy and safety of mepolizumab in Japanese patients with severe eosinophilic asthma.

BACKGROUND: The MENSA trial assessed the efficacy and safety of mepolizumab in patients with severe eosinophilic asthma. This report describes the efficacy and safety of mepolizumab in Japanese patients from MENSA. METHODS: A post hoc analysis of the Japanese subgroup from the randomized, double-blind, placebo-controlled, double-dummy, Phase III MENSA trial (NCT01691521). Patients ≥12 years with severe eosinophilic asthma received mepolizumab 75 mg intravenously (IV), 100 mg subcutaneously (SC), or placebo, every 4 weeks for 32 weeks. The primary endpoint was the annualized rate of exacerbations. Secondary and other endpoints included annualized rate of exacerbations requiring emergency department (ED) visit/hospitalization, morning peak expiratory flow (PEF), St George's Respiratory Questionnaire (SGRQ) score and eosinophil counts. Adverse events (AEs) were monitored. RESULTS: In the Japanese subgroup (N = 50), the rate of clinically significant exacerbations was reduced by 90% (rate ratio [RR]: 0.10; 95% confidence interval [CI]: 0.02-0.57; P = 0.010) with mepolizumab IV and 62% (RR: 0.38; 95% CI: 0.12-1.18; P = 0.094) with mepolizumab SC, versus placebo. No exacerbations requiring ED visit/hospitalization were reported with mepolizumab IV; exacerbations were reduced by 73% (RR: 0.27; 95% CI: 0.06-1.29; P = 0.102) with mepolizumab SC versus placebo. Compared with placebo, mepolizumab IV and SC numerically increased morning PEF from baseline by 40 L/min and 13 L/min, improved quality of life by greater than the minimal clinically important difference (SGRQ: 9.5 [P = 0.083] and 7.9 [P = 0.171] points) and reduced eosinophil counts. AE incidence was similar between treatments. Results were broadly consistent with the overall population. CONCLUSIONS: Mepolizumab was efficacious and well tolerated in Japanese patients with severe eosinophilic asthma, producing similar responses to the overall MENSA population.

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.

Asian Dust and Pediatric Emergency Department Visits Due to Bronchial Asthma and Respiratory Diseases in Nagasaki, Japan.

BACKGROUND: The adverse health effects of Asian dust (AD) on the respiratory system of children are unclear. We hypothesized that AD events may lead to increased visits by children to emergency medical centers due to bronchial asthma and respiratory diseases, including bronchial asthma. METHODS: We used anonymized data on children receiving primary emergency treatment at Nagasaki Municipal Primary Emergency Medical Center, Japan between March 2010 and September 2013. We used Light Detection and Ranging (LIDAR) data to assess AD exposure and performed time-stratified case-crossover analyses to examine the association between AD exposure and emergency department visits. The main analysis was done with data collected from March through May each year. RESULTS: The total number of emergency department visits during the study period was 756 for bronchial asthma and 5421 for respiratory diseases, and the number of "AD days" was 47. In school children, AD events at lag day 3 and lag day 4 were associated with increased emergency department visits due to bronchial asthma, with odds ratios of 1.837 (95% confidence interval [CI], 1.212-2.786) and 1.829 (95% CI, 1.179-2.806), respectively. AD events were significantly associated with respiratory diseases among preschool children at lag day 0, lag day 1, and lag day 2, with odds ratios of 1.244 (95% CI, 1.128-1.373), 1.314 (95% CI, 1.189-1.452), and 1.273 (95% CI, 1.152-1.408), respectively. These associations were also significant when the results were adjusted for meteorological variables and other air pollutants. CONCLUSIONS: The study findings suggested that AD exposure increases emergency department visits by children.

Impact of omalizumab on medical cost of childhood asthma in Japan.

Omalizumab is effective in children with severe asthma, but its impact on medical cost in Japan is not clear. We evaluated the impact of omalizumab on medical cost by comparing the pre- vs post-omalizumab-initiation medical costs of 12 children with severe asthma who received omalizumab for 2 years, and calculating incremental cost-effectiveness ratio for omalizumab therapy. Health outcome was measured as hospital-free days (HFD). The median total medical costs and medication fee per patient increased significantly after omalizumab initiation because of the high cost of omalizumab. The median hospitalization fee per patient, however, decreased significantly after omalizumab initiation due to reduction in hospitalization. Omalizumab led to an estimated increase of 40.8 HFD per omalizumab responder patient per 2 years. The cost was JPY 20 868 per additional HFD. Omalizumab can therefore reduce hospitalization cost in children with severe asthma in Japan.

Factors associated with the severity of childhood rhinoconjunctivitis.

BACKGROUND: Allergic rhinitis is one of the most common chronic diseases in children. Although it has a large impact on the patient's quality of life, little is known about the factors associated with its severity. The aim of this study was to assess the factors associated with the severity of rhinoconjunctivitis among children in the general population. METHODS: A survey was conducted using an online research panel in 2012. Parents were asked to answer an International Study of Asthma and Allergies in Childhood-based questionnaire to identify children with current rhinoconjunctivitis and evaluate factors associated with the severity of its symptoms. Severity was rated according to the degree of impairment caused by the symptoms in the patient's daily life. RESULTS: Among 26,725 children aged 6-12 years old, rhinoconjunctivitis was defined in 5175 (19.4%), and of these, 688 children (13.3% of children with current rhinoconjunctivitis) presented severe symptoms. Living in areas with a high cedar and cypress pollen count and having concurrent eczema were associated with severe rhinoconjunctivitis [adjusted OR (95% CI): 1.21 (1.00-1.46) and 1.45 (1.20-1.75), respectively]. Further, a maternal history of asthma and allergic rhinitis was a significant risk factor for severe rhinoconjunctivitis [1.34 (1.04-1.74) and 1.30 (1.10-1.53), respectively]. However, living with fur-bearing animals (pets) before 1 year of age proved to be a protective factor against severe rhinoconjunctivitis [0.70 (0.52-0.94)]. CONCLUSIONS: Environmental factors such as pets and pollen, together with comorbidities and a maternal history of allergic diseases, play an important role in determining the severity of rhinoconjunctivitis.

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.