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The relationship between exposure to polycyclic aromatic hydrocarbons and nasal symptoms currently remains unclear. Therefore, we herein examine this relationship in 51 adults living in Ishikawa prefecture, Japan, and conducted a 2 month follow-up survey on these participants. All participants were asked to record daily nasal symptoms in an allergy diary during the study period between 1 April to 31 May 2020. We collected air pollutant samples during the study period and determined the concentrations of PAHs and total suspended particulates by high-performance liquid chromatography. Sulfur dioxide and nitrogen dioxide concentrations were obtained through the Atmospheric Environmental Regional Observation System. We used generalized estimating equations to analyze the association between pollutant and nasal symptoms. After adjustment for confounding factors, the B values of fluoranthene, pyrene, and Benzo[k]fluoranthene were 2.389 (p = 0.026), 3.744 (p = 0.022) and 9.604 (p = 0.041), respectively, with a one-day lag. In contrast, the B value of indeno[1,2,3-cd]pyrene was −6.664 (p = 0.013) with no lag. Collectively, these results suggest ambient PAHs such as Flt, Pyr, and BkF were associated with nasal symptoms in adults. Further studies are needed to elucidate the mechanisms contributing to the relationships between specific PAHs and nasal symptoms. [ABSTRACT FROM AUTHOR]

Background: Childhood asthma is a major risk for low lung function in later adulthood, but what factors in asthma are associated with the poor lung function during childhood is not known. Objective: To identify clinical factors in children with asthma associated with low or declining lung function during the treatment. Methods: We enrolled children with asthma who had been treated throughout three age periods, i.e., 6–9, 10–12, and 13–15 years old, at seven specialized hospitals in Japan. Clinical information and lung function measurements were retrieved from the electronic chart systems. To characterize the lung function trajectories during each age period, we evaluated the forced expiratory volume 1 (FEV1) with % predicted values and individual changes by the slope (S) from linear regression. We defined four trajectory patterns: normal (Group N) and low (Group L), showing %FEV1 ≥80% or <80% throughout all three periods; upward (Group U) and downward (Group D), showing S ≥ 0 or S < 0%. Logistic regression analysis was performed to compare factors associated with the unfavorable (D/L) versus favorable (N/U) groups. Results: Among 273 eligible patients, 197 (72%) were classified into Group N (n = 150)/U (n = 47), while 76 (28%) were in Group D (n = 66)/L (n = 10). A history of poor asthma control, long-acting beta2 agonist use, and a lower height Z-score during 13–15 years were associated with an unfavorable outcome (Group D/L). Conversely, inhaled corticosteroid (ICS) use during 10–12 years and high-dose ICS use during 13–15 years were associated with a favorable outcome (Group N/U). Conclusion: We identified several factors that are associated with unfavorable lung function changes in pediatric asthma. Attention should be paid to the possible relationship between yearly changes in lung function and poor asthma control, use of ICS (and its dose) and use of LABA. [ABSTRACT FROM AUTHOR]

To clarify different effects of Asian dust (AD), long-range transported from Asian continent, on total suspended particles (TSP) and polycyclic aromatic hydrocarbons (PAHs) in Japan, TSP were simultaneously collected during AD periods (from 1 March to 31 May 2020 and 2021) in Fukuoka and Kanazawa. During AD days, decided by Light Detection and Ranging and Japan Meteorological Agency, TSP concentrations increased significantly (p < 0.001) at two sampling sites. PAH concentrations increased in Kanazawa (p < 0.001) but not in Fukuoka on AD days. Correlation coefficients (r) between daily TSP and total PAHs concentrations were weak in Kanazawa: 0.521 (non-AD) and 0.526 (AD) (p < 0.01), and in Fukuoka: 0.321 (non-AD) and 0.059 (AD). However, correlation between seasonal (average monthly) TSP and total PAH concentrations were stronger: 0.680 (Kanazawa) and 0.751 (Fukuoka). The reasons might be that seasonal variations of TSP and total PAHs in two cities depend equally on planetary scale westerly, while daily TSP and total PAHs variations in each city varied by different transportation distances from AD and PAHs sources in the Asian continent to Japan. Different local sources and meteorological conditions were considered. These results are important for elucidating the causes of chronic and acute respiratory diseases. [ABSTRACT FROM AUTHOR]

Rationale: Epidemiological evidence indicates that ambient exposure to particulate matter ⩽2.5 μm in aerodynamic diameter (PM2.5) has adverse effects on lung function growth in children, but it is not actually clear whether exposure to low-level PM2.5 results in long-term decrements in lung function growth in pre- to early-adolescent schoolchildren. Objectives: To examine long-term effects of PM2.5 within the 4-year average concentration range of 10-19 μg/m3 on lung function growth with repeated measurements of lung function tests. Methods: Longitudinal analysis of 6,233 lung function measurements in 1,466 participants aged 8-12 years from 16 school communities in 10 cities around Japan, covering a broad area of the country to represent concentration ranges of PM2.5, was done with a multilevel linear regression model. Forced expiratory volume in 1 second, forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC were used as lung function indicators to examine the effects of 10-μg/m3 increases in the PM2.5 concentration on relative growth per each 10-cm increase in height. Results: The overall annual mean PM2.5 level was 13.5 μg/m3 (range, 10.4-19.0 μg/m3). We found no association between any of the lung function growth indicators and increases in PM2.5 levels in children of either sex, even after controlling for potential confounders. Analysis with two-pollutant models with O3 or NO2 did not change the null results. Conclusions: This nationwide longitudinal study suggests that concurrent, long-term exposure to PM2.5 at concentrations ranging from 10.4 to 19.0 μg/m3 has little effect on lung function growth in preadolescent boys or pre- to early-adolescent girls. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: A relevant relationship exists between the upper and lower airway, indicating the concept of a unified airway. This study aimed to evaluate whether rhinitis has an association with asthma in children. METHODS: A cross-sectional nationwide survey was performed among children 6-7, 13-14, and 16-17 years old, using the International Study of Asthma and Allergies in Children (ISAAC) questionnaire in Japan. According to the responses to the ISAAC core questions, a child who had experienced nasal symptoms in the past 12 months in the absence of a cold was defined as having current rhinitis. RESULTS: After excluding 11,475 children because of incomplete data, 136,506 children were analyzed. Even after adjusting for demographics, sex, and obesity, children with current rhinitis were more likely to have asthma (adjusted odds ratio [OR], 3.10 [95% CI, 2.92-3.30] in children aged 6-7 years; OR, 3.76 [95% CI, 3.45-4.10] in children aged 13-14 years; and OR, 3.59 [95% CI, 3.33-3.88] in children aged 16-17 years). Children whose daily activities were more impaired by rhinitis symptoms had a significantly higher prevalence of severe asthma. The adjusted ORs for severe asthma among asthmatic children whose daily activities were severely impaired by rhinitis symptoms were 3.66 (95% CI, 2.29-5.85) in children aged 6-7 years, 2.55 (95% CI, 1.64-3.96) in children aged 13-14 years, and 1.87 (95% CI, 1.24-2.82) in children aged 16-17 years compared with asthmatic children whose daily activities were not impaired at all. CONCLUSION: There was a close association between rhinitis and asthma in young children to adolescents. Asthma should be examined in children with rhinitis symptoms. [ABSTRACT FROM AUTHOR]

Background. With an increase in Japanese cedar and cypress (JC) pollinosis, the relationship between JC pollen and atopic dermatitis (AD) has been studied. Some reports suggest that JC pollen can be one exacerbating factor for AD, but there has been no report that discusses JC pollen counts relating to AD symptom flare although actual airborne JC pollen counts can widely fluctuate throughout the pollen season. Objective. The relationship between symptom flare of AD and airborne JC pollen counts was examined. Methods. We monitored JC pollen counts in real time and divided the counts into low and high level. We then analyzed self-scored "itch intensity" recorded by 14 AD patients through a self-scoring diary. Results. Among the 14 patients, 7 had significantly higher itch intensity while the pollen counts were high. Conclusion. Even during the pollen season, actual airborne pollen counts can widely fluctuate. Our study suggested that symptom flare of AD could be influenced by the actual pollen counts. [ABSTRACT FROM AUTHOR]

Most studies regarding the association of obesity with asthma have been performed in the Western countries. This study is a nationwide survey conducted in Japan. A cross-sectional and questionnaire-based survey was performed among children aged 6-7, 13-14, and 16-17 years, using the ISAAC questionnaire. Overweight was defined as BMI ≥ 90th according to the reference values for Japanese children obtained during 1978-1981. Of a total of 179 218 children, 149 464 replied to the questionnaire (response rate 83.4%). After omitting incomplete data, 139 117 were analyzed. In all the age groups, being overweight was associated with current asthma after adjustment for confounding factors (adjusted OR: 1.24 in children 6-7 years of age, 1.31 in those 13-14 years, and 1.32 in those 16-17 years). These tendencies were observed in both genders. Overweight was a risk factor for nocturnal cough, independent of current asthma in the older age groups (adjusted OR: 1.21 in children 13-14 years, and 1.17 in those 16-17 years). There is a clear association between obesity and current asthma in Japanese school-aged children. Mechanisms through which obesity related with nocturnal cough might be different from those of obesity-associated asthma. [ABSTRACT FROM AUTHOR]

Background: Asthma is a common respiratory disease worldwide. However, few reports are available on the prevalences of asthma and asthma symptoms among Asian subjects. Methods: To determine the prevalences of asthma and asthma symptoms among Japanese subjects, we performed a nationwide cross-sectional, population-based study on Japanese adults aged 20-79 years. Ten areas spread throughout the country were randomly selected. Door-to-door or postal surveys were performed using a translated version of the European Community Respiratory Health Survey questionnaire. Results: The survey was completed by 23,483 participants. The overall response rate was 70.6%. The prevalences of wheeze and current asthma among all participants aged 20-79 years were 10.1% (95% CI: 9.7-10.5%) and 4.2% (95% CI: 4.0-4.5%), respectively. The prevalences among young adults aged 20-44 years were 9.3% (95% CI: 8.7-9.9%) and 5.3% (95% CI: 4.8-5.8%), respectively. The prevalence of current asthma was highest in females aged 30-39 years in comparison with the other gender and age groups. Conclusions: This nationwide study determined the prevalences of asthma and asthma symptoms among Japanese adults. The results provide fundamental information on the respiratory health of Japanese adults. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008 (JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008. In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity; recommendations for long-term management organized by age; a special mention of infantile asthma; and an emphasis on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report concerning JPGL 2005. [ABSTRACT FROM AUTHOR]

The aim was to investigate the effects of the 3-h mean concentration of suspended particulate matter (SPM) on peak expiratory flow (PEF) in asthmatic children. Subjects were 4- to 11-year-old boys and girls with asthma in Fukuoka, Japan. Daily measurements of PEF were made between April 2002 and March 2003. PEF was measured morning and evening. To assess the association between 3-h mean concentrations of SPM and morning PEF and evening PEF separately, we used generalized estimating equations. All models took into consideration seasonal effects: modified effects were examined using a two-level indicator variable for the warmer months (April through September) and the colder months (October through March). Among the 70 asthmatic children, 44 were boys. In warmer months, declines in morning PEF for 10 μg/m3 differences in 3-h concentration of SPM measured at 2 a.m. to 5 a.m. of the same day and 11 p.m. to 2 a.m. and 8 p.m. to 11 p.m. of the previous day were -0.78 L/min (95% CI: -1.40, -0.16), -0.61 L/min (-1.18, -0.05) and -0.73 L/min (-1.32, -0.15), respectively. Results were robust even after adjustment for other air pollutants. We also found that declines in evening PEF were weakly associated with increases in 3-h concentrations of SPM in warmer months, but the associations were not statistically significant. In colder months we did not find any robust association between SPM and morning/evening PEF. In conclusion, an increased 3-h concentration of SPM is associated with declines in PEF in warmer months. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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 (FEV 1) and Asthma Control Questionnaire (ACQ)-6 score. The safety of tezepelumab was also assessed. 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 FEV 1 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%). Tezepelumab reduced exacerbations compared with placebo, and was well tolerated, in NAVIGATOR patients with severe, uncontrolled asthma recruited in Japan. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 6th edition was published in 2009, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2009. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common chronic diseases in school-aged children in Japan. It is important to consider health-related quality of life (QoL) among children with chronic diseases when treatment decisions are made. Methods: A school-based survey was conducted in randomly selected public schools in Tokyo by using a KINDL® questionnaire for evaluating QoL and the international study of asthma and allergy on childhood (ISAAC) questionnaire, which is designed for comparing the asthma prevalence in various countries, from May to June in 2005. We recruited approximately 10% of the total children 6-7-years-old and 13-14-years-old living in Tokyo for sampling. Results: Response rate of this questionnaire was 86% (22,645 children) in the 6-7-year-old group and 64% (12,879 children) in the 13-14-year-old group. Comparing asthmatics with non-asthmatics in the same age, QoL of children with asthma was significantly impaired. The severity of QoL of children with asthma was significantly impaired. QoL of children with exercise-induced asthma (EIA) were more significantly impaired than ones without EIA and showed lower scores in the categories of physical functioning, emotional and school activities than those without EIA. Of note, QoL was more impaired in the EIA-positive group among severe asthmatics, suggesting that QoL of children with even severe asthma could be improved when EIA is appropriately controlled. Conclusions: Existence of EIA among asthmatic children most strongly impairs their QoL. We should be more cautious about the management of EIA. [ABSTRACT FROM AUTHOR]

Background: We conducted and reported the first (1982; 55,388 subjects), and second (1992; 45,674 subjects), epidemiological surveys conducted on bronchial asthma in elementary students across 11 prefectures in western Japan. The 2 surveys were conducted in the same regions using the same methodology employing a modified Japanese version of the American Thoracic Society-Division of Lung Diseases (ATS-DLD) Epidemiology Questionnaire. We conducted the third survey in 2002, and compared the findings to those of previous studies. Methods: In the third survey, 37,036 students attending the same schools as in previous surveys (in 11 prefectures) were given the questionnaire. A total of 35,582 responses (96.1%) were collected. An ATS-DLD Epidemiology Questionnaire was also used in this study, and the findings were compared to those of previous studies. Results: 1. The prevalence of bronchial asthma (BA) in boys, girls, and all students was 3.8%, 2.5%, and 3.2%, respectively, for the first survey; 5.6%, 3.5%, and 4.6% for the second survey; and 8.1%, 4.9%, and 6.5% for the third survey. 2. A decline in the BA prevalence in older subjects which could be seen in the first survey was absent in the second and third surveys. There were no regional differences in the third survey. 3. The boys-to-girls ratio in the first, second, and third surveys was 1.5, 1.6, and 1.6, respectively. 4. BA was more prevalent among subjects with a past history of respiratory disease in infancy and those with a family history of allergic disease. 5. The prevalence of asthma symptoms and wheezing in the first, second, and third surveys was 7.1%, 9.8%, and 11.8%, respectively. 6. A comparison of the prevalence of other allergic diseases between the second and third surveys revealed a decrease in atopic dermatitis and an increase in allergic rhinitis, allergic conjunctivitis, and cedar pollinosis. Conclusions: BA prevalence in the third survey increased 2.1 and 1.4 times respectively compared to the first survey and second survey, indicating an upward trend in all regions and age groups surveyed. [ABSTRACT FROM AUTHOR]

Rationale: Epidemiological evidence indicates that ambient exposure to particulate matter ⩽2.5 μm in aerodynamic diameter (PM 2.5 ) has adverse effects on lung function growth in children, but it is not actually clear whether exposure to low-level PM 2.5 results in long-term decrements in lung function growth in pre- to early-adolescent schoolchildren. Objectives: To examine long-term effects of PM 2.5 within the 4-year average concentration range of 10-19 μg/m 3 on lung function growth with repeated measurements of lung function tests. Methods: Longitudinal analysis of 6,233 lung function measurements in 1,466 participants aged 8-12 years from 16 school communities in 10 cities around Japan, covering a broad area of the country to represent concentration ranges of PM 2.5 , was done with a multilevel linear regression model. Forced expiratory volume in 1 second, forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC were used as lung function indicators to examine the effects of 10-μg/m 3 increases in the PM 2.5 concentration on relative growth per each 10-cm increase in height. Results: The overall annual mean PM 2.5 level was 13.5 μg/m 3 (range, 10.4-19.0 μg/m 3 ). We found no association between any of the lung function growth indicators and increases in PM 2.5 levels in children of either sex, even after controlling for potential confounders. Analysis with two-pollutant models with O 3 or NO 2 did not change the null results. Conclusions: This nationwide longitudinal study suggests that concurrent, long-term exposure to PM 2.5 at concentrations ranging from 10.4 to 19.0 μg/m 3 has little effect on lung function growth in preadolescent boys or pre- to early-adolescent girls.

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.

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.

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.

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., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

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., (Production and hosting by Elsevier B.V.)

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.

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 β 2 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.

Background: Omalizumab has demonstrated clinical benefits in children with moderate to severe allergic asthma. However, no studies have been performed in Japanese asthmatic children. The aim of this study was to evaluate the efficacy including free IgE suppression and safety of omalizumab in Japanese children with severe allergic asthma. The primary objective was to examine whether omalizumab decreases serum free IgE levels to less than 25 ng/ml (target level of suppression)., Methods: Thirty-eight Japanese children (6-15 years) with uncontrolled severe allergic asthma despite inhaled corticosteroids (>200 μg/day fluticasone propionate or equivalent) and two or more controller therapies received add-on treatment with omalizumab in a 24-week, multicenter, uncontrolled, open-label study., Results: The geometric mean serum free IgE level at 24 weeks was 15.6 ng/mL. Compared with baseline, total asthma symptom scores, daily activity scores and nocturnal sleep scores at 24 weeks were significantly improved. The rates of asthma exacerbation and hospitalization due to asthma were reduced by 69.2% and 78.2%, respectively (p < 0.001), versus baseline. Quality-of-life scores were also significantly improved (p < 0.001). In addition, 11 (28.9%) patients reduced the dose of any asthma controller medications. Thirty-six (94.7%) patients experienced at least one adverse event during the treatment period. All adverse events were mild or moderate in severity and no new safety concerns were detected. No patients discontinued the study., Conclusions: In Japanese children with severe allergic asthma, omalizumab decreased free IgE levels to less than 25 ng/mL. Omalizumab improved asthma control and was well-tolerated, as well., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Although achieving and maintaining control of asthma is considered to be the goal of asthma treatment, determinants of asthma control are not fully understood. Our aim was to assess factors associated with asthma control among paediatric patients in the general population., Methods: In June 2012, a Web-based survey was conducted to identify Japanese children aged 6 to 11 yr who currently have asthma and evaluate control of their disease using the Childhood Asthma Control Test (C-ACT). Associations were evaluated among uncontrolled asthma (C-ACT score <20) between environmental factors, demographics and comorbid allergic diseases., Results: Among the 3066 children with current asthma, 447 (14.6%) had uncontrolled asthma. Multivariable analysis identified factors such as low birthweight (adjusted OR 1.65, 95% CI 1.25-2.18), obesity (adjusted OR 1.44, 95% CI 1.05-1.99) and pet ownership before birth (adjusted OR 1.68, 95% CI 1.24-2.29) to be associated with uncontrolled disease. Comorbid allergic diseases, especially rhinitis were a significant risk of uncontrolled asthma (adjusted OR for severe rhinitis: 3.88, 95% CI 2.50-6.00). The severity of rhinitis symptoms was inversely correlated with the C-ACT score (p < 0.001)., Conclusions: A population-based Web survey showed an association between several factors and the control of paediatric asthma. The assessment of these factors may help identify the children at risk with uncontrolled asthma., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Epidemiologic studies have shown seasonal variations in responses to the written questionnaire for rhinitis symptoms., Objective: To evaluate whether the timing of data collection affected responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire in a Web-based study., Methods: The Web-based ISAAC questionnaires were completed by parents with children 6 to 12 years old using an online research system. The authors conducted surveys of asthma symptoms every month for 1 year and surveys of rhinitis and eczema symptoms every season throughout 1 entire year., Results: There was a significant fluctuation in the positive responses to questions about wheezing in the past 12 months (P < .001) but not in the positive responses to questions about exercise-induced wheezing in the past 12 months and asthma ever (P = .75 and P = .15, respectively). The positive responses to questions about rhinitis and allergic rhinoconjunctivitis in the past 12 months and pollinosis ever exhibited significant seasonal variations (P = .002, P < .001, and P < .001, respectively). In contrast, there were no significant variations in positive responses regarding eczema in the past 12 months and eczema ever (P = .33 and P = .55, respectively)., Conclusion: There were time-dependent fluctuations in responses to the Web-based questionnaire regarding allergic symptoms. Timing of data collection should be taken into account when evaluating prevalence of asthma and rhinitis in children., (Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 7th edition was published in 2013, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2013. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

Background: Exercise-induced wheezing (EIW) may be a symptom of asthma and is a predictor of exercise-induced bronchoconstriction, transient narrowing of the lower airway following exercise in the presence or absence of diagnosed asthma. Population-based studies with a large sample of EIW in relation to age, sex, current asthma severity and medication usage have been sparse., Methods: International Study of Asthma and Allergies in Childhood questionnaires were distributed at 885 nurseries, 535 primary schools, 321 junior high schools and 190 high schools, respectively, across Japan, and the corresponding data on 46,597, 41,216, 45,960 and 51,104 children were analyzed., Results: Prevalence of EIW was 4.8, 4.7, 17.9 and 15.4% for each of the four educational facility types, respectively. Among 24,103 current asthmatics, 20.9, 28.7, 76.1 and 73.6% of subjects for the 4 educational facility groups reported to have experienced EIW, respectively. Severity of current asthma was associated with the risk of EIW; odds ratio (95% confidence interval) of children with asthma attack every day for having EIW once a week or more, using intermittent asthmatics as reference group, were 24.48 (19.33 to 31.01) adjusted for other covariates. Among current asthmatic kindergartners, increase in risk for EIW due to ascending severity of current asthma was mitigated by daily use of leukotriene receptor antagonist (p for interaction = 0.071)., Conclusions: EIW was not rare among current asthmatic children. An increased risk for EIW was in accordance with increasing severity of current asthma and this relation was mitigated with leukotriene receptor antagonist daily use among kindergartners.

Obesity may increase the risk of subsequent asthma. We have previously reported that there is a clear association between obesity and asthma in Japanese school-aged children. To evaluate whether a similar association exists in younger children, a nationwide cross-sectional questionnaire-based survey was performed focusing on children aged 4-5 yr. A child who had experienced wheezing during the past 12 months and had ever been diagnosed with asthma by a physician was defined as having current asthma. Overweight and underweight were defined as BMI ≥90th percentile and ≤10th percentile, respectively, according to the reference values for Japanese children from 1978 to 1981. After excluding 2547 children because of incomplete data, 34,699 children were analyzed. Current asthma was significantly more prevalent in overweight children compared with underweight and normal weight children (13.2% for overweight vs. 10.5% for underweight and 11.1% for normal weight; both p < 0.001). Even after adjusting for other variables, such as gender, other coexisting allergic diseases, and parental history of asthma, there was an association between overweight and current asthma (adjusted odds ratio: 1.23, 95% CI: 1.10-1.38, p < 0.001). Even in preschool children, obesity is already associated with asthma, and there was no gender effect on this association. Physicians should consider the impact of obesity when managing asthma in younger children., (© 2011 John Wiley & Sons A/S.)

Background: It is important to clarify the quality of life (QOL) of the asthmatic children and their guardians., Method: We studied asthmatic patients treated at 359 institutes in Kyusyu and Okinawa, Japan, with QOL questionnaire 2 times in 2001. In the first study, 2906 patients were recruited and 2935 patients were in the 2nd study, and 1563 patients were in both study., Result: There was a statistically significant relationship, between the QOL and the clinical symptoms in the last 2 weeks, between the QOL and the severity of asthmatic symptoms, and between the patients' or their guardians' QOL and recognition of symptoms. There was a statistically significant relationship between the QOL answered by patients and those by guardians. More significant relationship of QOL between patients' and guardians' was seen in the patients with asthmatic attack or in the severe group, especially in schoolchildren., Conclusion: Asthmatic control is important for improvement of QOL. Because correlation is significant in QOL between parent and child especially in schoolchildren, asthmatic control is particularly important.

In order to analyze the determinants involved in the development of allergic diseases early in infancy, we examined the environmental and genetic factors that might affect the induction of such diseases during infancy, using a questionnaire. Maternal pharyngitis during pregnancy was significantly related to the development of atopic dermatitis in their progeny. Moreover, the frequency of the maternal infection was associated with a significantly increased risk of allergy in their infants. The prevalence of post-delivery maternal allergy was positively linked to the allergic symptoms in their children while the likelihood of bearing allergic children was related to the numbers of allergic individuals within their family. These results suggested that pre- and post-natal maternal factors and any genetic predisposition might modify the development of allergy in infancy.