Association between allergen-specific immunoglobulin E positivity, allergic rhinitis symptoms, and quality of life in school-aged children

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We analyzed data from 8-year-old children who participated in the Yamanashi Adjunct Study of the Japan Environment and Children's Study, focusing on those with complete information o on specific IgE levels and AR (1,229 for perennial AR [PAR] and 1,196 for seasonal AR [SAR]). Sensitization was determined when allergen-specific IgE levels were class 2 (0.70 U/mL) or higher. Among those who tested positive for house dust mite (HDM)-specific IgE, 656 (53.4%) children were identified, including 362 (60.6%) boys and 294 (46.5%) girls. For Japanese cedar pollen (JCP)-specific IgE, 820 (68.6%) children were sensitized, with 430 (73.1%) boys and 390 (64.1%) girls. Among children with AR, 38.3% of those with PAR and 76.2% of those with SAR experienced moderate to severe nasal symptoms. This study highlighted the high prevalence of JCP-specific IgE sensitization among school-aged children in Japan and provided insights into the severity of AR symptoms and the impact on QOL in these children. Health sciences/Medical research/Epidemiology Health sciences/Health care/Public health/Epidemiology Allergic Rhinitis Quality of Life School-aged Children Seasonal allergic rhinitis (SAR) Severity Specific IgE Antibodies Figures Figure 1 Figure 2 Figure 3 Introduction Allergic rhinitis (AR) has been rapidly increasing worldwide, emerging as a significant health and social issue. In Denmark, AR prevalence among adults rose from 19–32% over the past 30 years [ 1 ]. A recent meta-analysis reported an increase in AR prevalence among children from 8.39% during 2012–2015 to 19.87% during 2016–2022 [ 2 ]. In Japan, Japanese cedar pollen (JCP) is the most common cause of AR, making it a national health concern. A survey of otolaryngologists and their families in Japan showed that JCP allergy prevalence increased from 16.2% in 1998 to 26.5% in 2008 and to 38.3% in 2019 [ 3 ]. Furthermore, among children aged 5–9 years, the prevalence of JCP allergy rose from 7.5% in 1998 to 30.1% in 2019, with the age of onset decreasing [ 3 ]. Traditionally, AR has been classified mainly into perennial AR (PAR) and seasonal AR (SAR) based on the exposure period [ 4 ]. PAR is caused by indoor allergens, such as house dust mites (HDM), mold, and pet dander, leading to year-round symptoms. Conversely, SAR is triggered by outdoor allergens, such as cedar, cypress, and grass pollen, causing symptoms during specific seasons when pollen is dispersed. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines classify AR as intermittent and persistent. Intermittent AR involves symptoms for less than 4 days a week or fewer than 4 consecutive weeks, whereas persistent AR presents symptoms for more than 4 days per week and over 4 weeks. AR is characterized by sneezing, nasal congestion, nasal itching, and rhinorrhea, all triggered by an immunoglobulin E (IgE)-mediated response to inhaled allergens [ 5 ]. Therefore, diagnosing AR involves a medical interview and IgE antibody measurement to assess AR risk. Several European birth cohort studies have reported IgE levels for various allergens in children [ 6 , 7 ]. However, in Japan, only one study has measured IgE levels for multiple allergens in children aged 5–9 years living in Tokyo [ 8 ]. AR significantly impacts health-related quality of life (HRQOL). According to the ARIA recommendations, the severity of AR should be assessed by considering its impact on HRQOL [ 9 ]. AR causes absenteeism from work and school, non-productive time, sleep disorders, and reduced participation in outdoor activities [ 10 – 12 ]. Additionally, children with AR may experience declines in learning ability and academic performance [ 13 , 14 ]. This study aimed to investigate the prevalence of HDM- and JCP-specific IgE positivity and its association with AR symptoms among schoolchildren in Yamanashi Prefecture, which has the highest prevalence of JCP allergy in Japan. Additionally, this study sought to assess the severity of symptoms and QOL in children with AR and to provide up-to-date descriptive epidemiological data. Methods Participants The Japan Environment and Children’s Study (JECS) is a nationwide birth cohort study organized by the JECS Working Group to investigate environmental factors affecting children’s health and development. Pregnant women were recruited between January 2011 and March 2014 at 15 Regional Centers covering 19 prefectures across Japan, resulting in over 100,000 participants. We belong to the Koshin Regional Centers, which include Yamanashi and Nagano prefectures, and are responsible for conducting research on participants in Yamanashi Prefecture. Detailed protocols have been published previously [ 15 , 16 ]. Between July 2019 and November 2022, we conducted an additional survey with participants in Yamanashi Prefecture when each child reached the age of 8 years. However, due to the impact of coronavirus disease 2019 (COVID-19), no surveys were conducted between March and June 2020. This additional survey included ophthalmological exams, oral examinations, and blood tests. In July 2023, a survey on AR symptoms was mailed to additional research participants, with responses obtained by April 2024. At the time of the survey, participants were aged 8–12 years. Of the 2,036 additional survey participants, 1,531 were eligible for analysis after excluding those for whom specific IgE measurements could not be obtained. Furthermore, after excluding participants who did not respond to the PAR and SAR questionnaires, the numbers were reduced to 1,229 and 1,196 individuals, respectively. To assess the severity of AR symptoms, individuals with symptoms of either PAR (n = 345) or SAR (n = 866) were selected from each group (Supplementary Figure S1 ). The JECS protocol was reviewed and approved by the Ministry of the Environment’s Institutional Review Board for Epidemiological Studies and the Ethics Committees of all participating institutions (ethical approval number: 100910001). Additionally, this study was approved by the Institutional Review Board of Yamanashi University (No. 2070, 2218, and 2689). The study adhered to the principles of the Declaration of Helsinki, and informed consent was obtained from all subjects and/or their legal guardian(s). Measurement of Total and allergen-specific IgE We collected venous blood samples from 8-year-old children. Total IgE and allergen-specific IgE titers were measured using the ImmunoCAP system (SRL, Tokyo, Japan). Total IgE and specific IgE titers for HDM ( Der p 1) or JCP allergens were measured using the ImmunoCAP system (SRL, Tokyo, Japan). IgE levels for Dermatophagoides pteronyssinus ( Der p ) and JCP allergens were classified into seven categories: class 0 (< 0.35 UA/mL), class 1 (0.35–0.69 UA/mL), class 2 (0.70–3.49 UA/mL), class 3 (3.5–17.49 UA/mL), class 4 (17.5–49.99 UA/mL), class 5 (50–99.99 UA/mL), and class 6 (≥ 100 UA/mL). Positive IgE sensitization to allergens was defined as class 2 or higher. Investigation of AR symptoms Data on AR symptoms during school age were collected using a self-administered questionnaire completed by the mothers. They were asked to indicate whether the child currently had PAR (caused by dust mites, house dust, etc., resulting in year-round nasal or eye symptoms) and/or SAR (caused mainly by pollen, resulting in nasal or eye symptoms during specific seasons, commonly known as hay fever) by selecting one of the following options: "Diagnosed at a hospital and receiving treatment," "Diagnosed by a hospital, but not treated," "Symptomatic but has not seen a doctor," "No symptoms," or "Undecided." For mothers reporting that their child had symptoms of either type of AR, additional questions were asked to assess the severity of the child's AR and its impact on their QOL. Evaluation of the severity and quality of life (QOL) in PAR Mothers were asked to indicate how many years had passed since their child was first diagnosed with PAR or began experiencing nasal or eye symptoms by choosing from the following options: "Less than 6 months," "6 months to less than 1 year," "1 year to less than 2 years," "2 years to less than 3 years," "3 years to less than 4 years," "4 years to less than 5 years," "5 years to less than 10 years," and "10 years or more." Mothers were asked the following question: "How often does your child experience sneezing and nose blowing on an average day? Please provide an approximate number of times per day based on recent observations." The response options were: "Almost never," "1–5 times," "6–10 times," "11–20 times," and "More than 21 times." Additionally, regarding nasal congestion, mothers were asked: "How often does your child experience nasal congestion? Please describe the recent situation." The response options were: "Almost never," "Some nasal congestion, but no mouth breathing (can breathe through the nose)," "Severe nasal congestion, occasional mouth breathing (cannot always breathe through the nose)," "Very severe nasal congestion, frequent mouth breathing (mostly breathes through the mouth)," and "Completely congested all day." The severity of AR symptoms was classified based on the Nasal Allergy Guidelines of the Japan Society of Immunology Allergology and Infection in Otorhinolaryngology, categorizing them as none, mild, moderate, severe, and severest. To evaluate the impact on daily life, mothers were asked: "How much do your child's nasal or eye symptoms affect their daily life (studying, outdoor activities, or sleep)?" The response options were: "None," "Slightly," "Significantly," and "Impossible." Evaluation of the severity and quality of life (QOL) in SAR Mothers were asked to indicate how many years had passed since their child was first diagnosed with hay fever or began experiencing nasal or eye symptoms, using the same options provided for PAR. Additionally, mothers were asked to indicate all the months during which their child experienced hay fever symptoms throughout the year. During the period when symptoms occurred, mothers were also asked to provide responses regarding sneezing attacks, frequency of nose blowing, and the condition of nasal congestion, using the same options provided for PAR symptoms, and severity classification was conducted. Additionally, mothers were asked about the impact of nasal or eye symptoms on their child's studying, outdoor activities, and sleep, using the same options provided for PAR symptoms. Statistical analyses The sex of the children was extracted from the medical records of the dataset jecs-ta-20190930-qsn, released in October 2019 and finalized in March 2022. Sex was cross-tabulated with allergen-specific IgE or nasal symptoms, and the relationship was evaluated using the chi-square test. The Mann-Whitney U test was used to compare nonspecific IgE levels according to sex. Statistical significance was set at a p-value of 0.05 (two-sided). All statistical analyses were conducted using Statistical Package for the Social Sciences software version 27.0 (IBM Corp., Armonk, NY, USA). Results Table 1 shows the cross-tabulation by sex for HDM-specific IgE sensitization and PAR symptoms. A total of 656 (53.4%) children were positive for HDM-specific IgE sensitization, including 362 (60.6%) boys and 294 (46.5%) girls. A comparison of the median levels of nonspecific IgE showed that boys had higher nonspecific IgE levels than girls. For PAR symptoms, 345 (28.1%) children had symptoms overall, with 194 (32.5%) boys and 151 (23.9%) girls. Supplementary Table S1 shows the cross-tabulation of HDM-specific IgE sensitization and PAR symptoms: 69 (12.0%) children who tested negative for HDM-specific IgE had PAR symptoms, whereas 380 (57.9%) children with positive HDM-specific IgE showed no PAR symptoms. Table 1 Characteristics of house dust mite (HDM)-specific IgE and perennial allergic rhinitis symptoms All 1,229 (100) Boys 597 (48.6) Girls 632 (51.4) p-value HDM-specific IgE Negative 573 (46.6) 235 (39.4) 338 (53.5) < 0.001 Positive 656 (53.4) 362 (60.6) 294 (46.5) Class 0 523 (42.6) 210 (35.2) 313 (49.5) < 0.001 Class 1 50 (4.1) 25 (4.2) 25 (4.0) Class 2 123 (10.0) 60 (10.1) 63 (10.0) Class 3 165 (13.4) 85 (14.2) 80 (12.7) Class 4 179 (14.6) 102 (17.1) 77 (12.2) Class 5 128 (10.4) 79 (13.2) 49 (7.8) Class 6 61 (5.0) 36 (6.0) 25 (4.0) Non-specific IgE (IU/mL) 181.0 (55.6–471.0) 235.0 (77.9–603.0) 135.0 (46.1–365.5) < 0.001 Missing data 22 (1.8) 6 (1.0) 16 (2.5) Symptoms of perennial allergic rhinitis No symptoms 766 (62.3) 356 (59.6) 410 (64.9) 0.005 Undecided 118 (9.6) 47 (7.9) 71 (11.2) Diagnosed at a hospital and receiving treatment 186 (15.1) 108 (18.1) 78 (12.3) Diagnosed by a hospital, but not treated 92 (7.5) 53 (8.9) 39 (6.2) Symptomatic but has not seen a doctor 67 (5.5) 33 (5.5) 34 (5.4) n (%) or median (IQR). p-values were obtained from the chi-square test or Mann-Whitney U test. Figure 1 shows the duration and severity of PAR symptoms along with their impact on QOL. The most common duration of PAR symptoms was 5–10 years, affecting 39.1% of the children (38.1% of boys and 40.4% of girls), with no significant sex differences. Symptom severity was classified as follows: no symptoms (16.5%), mild (40.9%), moderate (24.1%), severe (11.6%), and very severe (2.6%), with no sex differences in severity. The impact of PAR symptoms on studying, outdoor activities, and sleep was: 67.2%, 70.7%, and 60.9% experienced no impact; 27.8%, 25.2%, and 33.0% experienced a slight impact; and 3.2%, 2.3%, and 3.8% experienced a considerable impact, respectively. No significant differences were observed between boys and girls regarding QOL impacts. Table 2 shows the cross-tabulation by sex for JCP-specific IgE sensitization and SAR symptoms. A total of 820 (68.2%) children were positive for JCP-specific IgE sensitization, including 430 (73.1%) boys and 390 (64.1%) girls. Supplementary Table S2 details the cross-tabulation of JCP-specific IgE sensitization and SAR symptoms: 166 (44.1%) children negative for JCP-specific IgE had SAR symptoms, whereas 120 (14.6%) children positive for JCP-specific IgE showed no SAR symptoms. Figure 2 shows the proportion of JCP-specific IgE class levels by month of blood sampling, with June showing the highest sensitization proportion (79.6%) and August the lowest (58.7%). Table 2 Characteristics of Japanese cedar pollen (JCP)-specific IgE and seasonal allergic rhinitis symptoms All 1,196 (100) Boys 588 (49.2) Girls 608 (50.8) p-value JCP-specific IgE Negative 376 (31.4) 158 (26.9) 218 (35.9) 0.001 Positive 820 (68.6) 430 (73.1) 390 (64.1) Class 0 333 (27.8) 141 (24.0) 192 (31.6) 0.007 Class 1 43 (3.6) 17 (2.9) 26 (4.3) Class 2 131 (11.0) 66 (11.2) 65 (10.7) Class 3 241(20.2) 113 (19.2) 128 (21.1) Class 4 227 (19.0) 131 (22.3) 96 (15.8) Class 5 137 (11.5) 71 (12.1) 66 (10.9) Class 6 84 (7.0) 49 (8.3) 35 (5.8) Non-specific IgE (IU/mL) 182.0 (57.5–472.5) 239.0 (80.8–609.5) 135.0 (46.2–354.0) < 0.001 Missing data 19 (1.6) 5 (0.9) 14 (2.3) Symptoms of seasonal allergic rhinitis No symptoms 280 (23.4) 133 (22.6) 147 (24.2) 0.06 Undecided 50 (4.2) 22 (3.7) 28 (4.6) Diagnosed at a hospital and receiving treatment 508 (50.8) 311 (52.9) 297 (48.8) Diagnosed by a hospital, but not treated 143 (12.0) 78 (13.3) 65 (10.7) Symptomatic but has not seen a doctor 115 (9.6) 44 (7.5) 71 (11.7) n (%) or median (IQR). p-values were obtained from the chi-square test or Mann-Whitney U test. Figure 3 shows the duration and severity of SAR symptoms along with their impact on QOL. The most common duration of SAR symptoms was 5–10 years, affecting 35.7% of the children (36.5% of boys and 34.9% of girls), with no significant sex differences. Symptom severity was classified as follows: no symptoms (3.0%), mild (17.1%), moderate (31.3%), severe (29.9%), and very severe (15.0%), with no sex differences in severity. The impact of SAR symptoms on studying, outdoor activities, and sleep was: 39.8%, 41.5%, and 39.0% experienced no impact; 51.0%, 46.7%, and 49.5% experienced a slight impact; 8.9%, 11.7%, and 11.1% experienced a considerable impact; and 0.1%, 0.1%, and 0.2% experienced an impossible impact. Table 3 shows the number of children with IgE polysensitization to HDM and JCP. Moreover, 367 (23.8%) children were HDM(-)JCP(-), 119 (7.7%) were HDM(+)JCP(-), 336 (21.8%) were HDM(-)JCP(+), and 717 (46.6%) were HDM(+)JCP(+). The proportion of IgE polysensitization to HDM and JCP was higher in boys than in girls. Table 3 Co-sensitization to house dust mite (HDM)- and Japanese cedar pollen (JCP)-specific IgE All 1,539 (100) Boys 769 (50.0) Girls 770 (50.0) p-value HDM (-) JCP (-) 367 (23.8) 138 (17.9) 229 (29.7) < 0.001 HDM (+) JCP (-) 119 (7.7) 67 (8.7) 52 (6.8) HDM (-) JCP (+) 336 (21.8) 157 (20.4) 179 (23.2) HDM (+) JCP (+) 717 (46.6) 407 (52.9) 310 (40.3) p-values were obtained from the chi-square test. Discussion This study represented the first investigation of HDM-specific and JCP-specific IgE along with AR symptoms in healthy school-age children. Among 8-year-olds in the study area, 68.2% were sensitized to JCP-specific IgE, with a higher prevalence in boys compared to girls. Furthermore, children with SAR exhibited more severe rhinitis and greater impacts on their QOL concerning studying, outdoor activities, and sleep compared to those with PAR. Typically, blood IgE levels are measured when patients with suspected allergies visit hospitals. However, due to challenges in accurately assessing symptoms and reluctance to undergo blood sampling, opportunities to obtain blood samples from children are limited. Consequently, reports on the prevalence of IgE sensitization in the general population are scarce. A meta-analysis of five European birth cohorts reported that 25– 45% of 8–10-year-olds are sensitized to inhalant allergens [ 2 ]. A French cohort study reported that approximately 20% of 8–9-year-olds have HDM-specific IgE sensitization [ 7 ]. In a prospective birth cohort study of the general population, called the Tokyo Children’s Health, Illness and Development study (T-Child study), the percentage of 9-year-olds sensitized to Der f 1-specific IgE is 54.3% [ 3 ], a figure comparable to our study’s result of 53.4%. The hot and humid climate in Japan, which facilitates mites proliferation, likely contributes to higher rates of IgE sensitization to mites compared to Europe and America [ 17 ]. In Japan, cedar and cypress are the most common pollen allergy-causing plants. Cedar pollen allergen Cry j 1 cross-reacts with cypress pollen allergen Cha o 1, leading many individuals with cedar pollen allergies to also react to cypress pollen [ 18 ]. In the T-Child study, the percentage of 9-year-olds sensitized to JCP-specific IgE is 57.8%, which is lower than the 68.6% found in our study [ 3 ]. This difference could be due to regional differences, as the Yamanashi Prefecture, where our study was conducted, is surrounded by forests with high levels of cedar and cypress pollen. A 2019 nationwide survey identified Yamanashi Prefecture as having the highest prevalence of JCP allergy in Japan [ 3 ]. The JECS study, which surveyed approximately 88,000 pregnant women across Japan, found a national average sensitization rate to JCP-specific IgE of 50.9%. In contrast, the Koshin region, including Yamanashi and Nagano Prefectures, showed the highest rate at 67.0% [ 19 ]. By the age of 8 years, the proportion of children with JCP-specific IgE sensitization was already comparable to that of adults. Most previous studies have measured JCP-specific IgE during the pollen dispersal period. In this study, blood samples were collected around the participants' 8th birthday between July 2019 and November 2022, measuring allergen-specific IgE levels. A distinctive aspect of our study was the measurement of JCP-specific IgE both during and outside the cedar pollen season, which may have led to an underestimation of the JCP-specific IgE sensitization positivity rate. The JCP dispersal period is from February to April when pollen levels peak. According to the survey results for the period when pollen allergy symptoms appeared (Supplementary Figure S2), cedar and cypress pollen were the causes, as most patients with pollen allergy exhibited symptoms from February to May. In contrast, approximately 30% of patients exhibited symptoms between September and November, suggesting ragweed and mugwort pollen as possible triggers. The positivity rate for JCP-specific IgE increased from September to November (Fig. 2 ), possibly due to "crazy blooming," where warm autumns lead to out-of-season flowering [ 20 , 21 ], leading to JCP exposure even in the fall. Additionally, approximately 60% of children tested positive for JCP-specific IgE sensitization even during the non-dispersal period, suggesting persistent high IgE levels throughout the year. Meta-analyses have shown sex differences in the prevalence of AR, with rates in males during childhood and in females during adolescence [ 22 ]. A survey of a healthy population aged 20–59 years living in Tokyo, Japan [ 23 ], found a 38.3% overall sensitization rate to HDM-specific IgE (≥ 0.35 UA/mL), with males showing a significantly higher rate than females. The overall sensitization rate to JCP-specific IgE was 66.8%, with no significant sex differences across age groups, though males aged 20– 29 had a notably higher rate than females. These findings align with our results, showing that 8-year-old boys had higher sensitization rates for both HDM-specific IgE (odd s ratio [OR]: 1.77, 95% confidence interval [CI]: 1.41–2.22) and JCP-specific IgE (OR: 1.52, 95% CI: 1.19–1.95) compared to girls. Additionally, we uniquely revealed that boys had a higher proportion of polysensitization to both HDM-specific and JCP-specific IgEs, whereas girls had a higher proportion of sensitization exclusively to JCP-specific IgE. SAR is typically associated with more acute and severe symptoms than PAR due to high pollen exposure over a short period. Our study found that 85.4% of children with JCP-specific IgE sensitization had AR symptoms, whereas only 42.1% of those sensitized to HDM-specific IgE had such symptoms, indicating a significant difference between sensitization and the presence of symptoms. Furthermore, among children with AR, 76.2% of those with SAR had moderate to severe symptoms, compared to 38.3% of those with PAR. In a survey conducted in 2017 targeting patients with AR, the proportion of moderate or severe cases among those aged 15–19 years is 63.0% for PAR and 61.6% for SAR [ 24 ]. In comparison, our study revealed lower severity for PAR, potentially due to an underestimation of PAR severity relative to SAR in children with both conditions. The main symptoms of AR, including sneezing, nasal itching, rhinorrhea, and nasal congestion [ 25 ], are associated with sleep deprivation [ 26 ], fatigue [ 27 ], and mental health issues [ 28 ] in patients with AR. The relationship between AR and sleep disturbances is well-documented in adolescents, with AR children experiencing shorter nighttime sleep duration [ 29 , 30 ] and increased daytime sleepiness [ 11 , 31 ]. Moreover, as rhinitis severity increases, academic performance often declines due to reduced classroom productivity [ 11 , 13 ]. Our results indicated that approximately 75% of children with pollen allergies experienced moderate to severe AR symptoms, with approximately 60% affected in their sleep, outdoor activities, and studying, highlighting a serious issue. However, appropriate interventions for AR may improve both the severity of AR and QOL. In particular, allergen-specific immunotherapy (AIT) improves AR symptoms, QOL, and performance at work/school [ 32 – 35 ]. Sublingual immunotherapy (SLIT), a type of AIT, has rapidly gained acceptance in recent years owing to its minimal adverse effects and convenient administration. In Japan, the starting age for SLIT was lowered to 5 years old in 2018 [ 26 ], making it a viable option for improving QOL and academic outcomes in children, provided safe long-term adherence to medication is ensured. The strength of this study lies in its investigation of the relationship between allergen-specific IgE sensitization and AR symptoms among elementary school students in the region with the highest prevalence of hay fever in Japan. Additionally, this study elucidated the severity of AR and its impact on the QOL among patients with AR. Opportunities to collect blood samples from typically healthy 8-year-old children are limited, making the measurement of IgE levels and the calculation of sensitization rates in this age group a valuable data resource. Nevertheless, this study had some limitations. Firstly, the diagnosis and symptoms of AR relied on self-reported questionnaires completed by mothers, which could have led to potential misclassification. Secondly, blood samples were collected when the children were 8 years old, whereas the symptom questionnaires were completed when the children were between 8 and 12 years old, raising the possibility that some children who developed AR symptoms after the age of 8 were included. However, considering the results regarding symptom duration, most children likely experienced rhinitis symptoms before the age of 8 years. Thirdly, although we investigated the impact of AR on children's QOL regarding studying, outdoor activities, and sleep, the external validity of the questions remained uncertain. The Japanese Rhinitis Quality of Life Questionnaire (JRQLQ No1), commonly used for assessing QOL in AR, was not utilized in this study because it is designed for patients visiting medical institutions and is not suitable for evaluating healthy school-age children. Finally, although some AR symptoms could have been triggered by unmeasured allergens, approximately 85% of children with SAR symptoms reported experiencing them in March and April, suggesting that most children with SAR were likely sensitized to pollen allergens such as cedar and cypress. Conclusions This study revealed the prevalence of sensitization to HDM- and JCP-specific IgE and the current state of AR symptoms among 8-year-old children in the region with the highest number of patients with hay fever in Japan. Children with cedar pollen allergies experienced significant negative impacts on sleep and academic performance, making early prevention and treatment from infancy essential. Further follow-up studies from school age onwards are necessary to elucidate the effects of treatment on symptoms and QOL. Declarations Competing interests The authors declare that they have no conflict of interest. Funding This research received support from a Grant-in-Aid for Scientific Research conferred by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (No. 20H03928, 24K13437) and TERUMO LIFE SCIENCE FOUNDATION (23-Ⅲ5024). The JECS was funded by the Ministry of the Environment, Japan. The findings and conclusions of this study are solely the responsibility of the authors and do not represent the official views of the above-mentioned government. Author Contribution KM conceived the study design. DW and KM performed statistical analysis and drafted the initial manuscript. DW, KM, SO, MK, HY, RS, and ZY collected the data. DW, KM, SO, MK, HY, RS, ZY, DW, DS and the JECS critically reviewed and revised the manuscript. All authors have approved the final manuscript as submitted and agree to be accountable for all aspects of this work. Acknowledgement We express our gratitude to every participant in the JECS and appreciate the contributions of all individuals engaged in data collection. We would like to thank Keiko Mitsui and Ayumi Okada for their technical support in data collection and cleaning. We would like to thank Editage (www.editage.jp) for English language editing. Data Availability Data are unsuitable for public deposition due to ethical restrictions and legal framework of Japan. It is prohibited by the Act on the Protection of Personal Information (Act No. 57 of 30 May 2003, amendment on 9 September 2015) to publicly deposit the data containing personal information. Ethical Guidelines for Epidemiological Research enforced by the Japan Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare also restrict the open sharing of the epidemiologic data. All inquiries about access to data should be sent to: [email protected] . The person responsible for handling enquiries sent to this e-mail address is Dr Shoji F. Nakayama, JECS Programme Office, National Institute for Environmental Studies. References Leth-Møller, K. B., Skaaby, T. & Linneberg, A. Allergic rhinitis and allergic sensitisation are still increasing among Danish adults. Allergy . 75 , 660–668 (2020). Licari, A. et al. Epidemiology of allergic rhinitis in children: A systematic review and meta-analysis. J. Allergy Clin. Immunol. Pract. 11 , 2547–2556 (2023). Matsubara, A. et al. Epidemiological survey of allergic rhinitis in Japan 2019. Nippon Jibiinkoka Gakkai Kaiho 123, 485 – 90 (2020). Meng, Y., Wang, C. & Zhang, L. Advances and novel developments in allergic rhinitis. Allergy . 75 , 3069–3076 (2020). Bousquet, J. et al. Allergic rhinitis. Nat. Rev. Dis. Primers . 6 , 95 (2020). Gruzieva, O. et al. Meta-analysis of air pollution exposure association with allergic sensitization in European birth cohorts. J. Allergy Clin. Immunol. 133 , 767–776 (2014). Gabet, S. et al. Asthma and allergic rhinitis risk depends on house dust mite specific IgE levels in Paris birth cohort children. World Allergy Organ. J. 12 , 100057 (2019). Yamamoto-Hanada, K. et al. IgE responses to multiple allergen components among school-aged children in a general population birth cohort in Tokyo. World Allergy Organ. J. 13 , 100105 (2020). Bousquet, J. et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 63 Supplement 86, 8-160 (2008). Vandenplas, O. et al. Impact of rhinitis on work productivity: a systematic review. J. Allergy Clin. Immunol. Pract. 6 , 1274–1286e9 (2008). Devillier, P. et al. In allergic rhinitis, work, classroom and activity impairments are weakly related to other outcome measures. Clin. Exp. Allergy . 46 , 1456–1464 (2016). Pagel, J. M. L. & Mattos, J. L. Allergic rhinitis and its effect on sleep. Otolaryngol. Clin. North. Am. 57 , 319–328 (2024). Walker, S. et al. Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case–control study. J. Allergy Clin. Immunol. 120 , 381–387 (2007). Blaiss, M. S., Hammerby, E., Robinson, S., Kennedy-Martin, T. & Buchs, S. The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review. Ann. Allergy Asthma Immunol. 121 , 43–52e3 (2018). Kawamoto, T. et al. Rationale and study design of the Japan environment and children's study (JECS). BMC Public. Health . 14 , 25 (2014). Michikawa, T. et al. Baseline profile of participants in the Japan Environment and Children's Study (JECS). J. Epidemiol. 28 , 99–104 (2018). Fukutomi, Y., Yasueda, H., Nakazawa, T., Taniguchi, M. & Akiyama, K. Indoor mite and insect allergens and allergic disease. Indoor Environ. 12 , 87–96 (2009). Sone, T. et al. Identification of human T cell epitopes in Japanese cypress pollen allergen, Cha o 1, elucidates the intrinsic mechanism of cross-allergenicity between Cha o 1 and Cry j 1, the major allergen of Japanese cedar pollen, at the T cell level. Clin. Exp. Allergy . 35 , 664–671 (2005). Yamamoto-Hanada, K. et al. Allergic profiles of mothers and fathers in the Japan Environment and Children's Study (JECS): a nationwide birth cohort study. World Allergy Organ. J. 10 , 24 (2017). Takahashi, Y. Current state of Japanese cedar (Cryptomeria japonica D. Don) pollen information and future directions for its airborne allergen determination and improved pollen monitoring. Aerobiology . 2 , 1–17 (2024). Taira, H., Yoshii, E. & Teranishi, H. The Characteristic of the pollen dispersal of cryptomeria japonica. Arerugi . 53 , 1187–1194 (2004). Fröhlich, M. et al. Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from childhood to adulthood? A meta-analysis. Clin. Transl Allergy . 7 , 44 (2017). Tanaka, J. et al. Prevalence of inhaled allergen-specific IgE antibody positivity in the healthy Japanese population. J. Allergy Clin. Immunol. 133 , 632–9e5 (2014). Okamoto, Y., Ohta, T., Karim, Y., Kaneko, Y. & Yoden, T. Survey of patient awareness and actions for improved quality of life in perennial allergic rhinitis. Ther. Res. 38 , 1001–1037 (2017). Okubo, K. et al. Japanese guidelines for allergic rhinitis 2020. Allergol. Int. 69, 331 – 45 (2020). Liu, J., Zhang, X., Zhao, Y. & Wang, Y. The association between allergic rhinitis and sleep: A systematic review and meta-analysis of observational studies. PLOS ONE . 15 , e0228533 (2020). Kim, O., Kim, B., Jeong, H., Lee, J. & Jung, H. Sleep, fatigue, and depressive symptoms among female nurses with allergic rhinitis. Healthc. (Basel) . 9 , 1328 (2021). Amritwar, A. U. et al. Mental health in allergic rhinitis: depression and suicidal behavior. Curr. Treat. Options Allergy . 4 , 71–97 (2017). Kwon, J. A., Lee, M., Yoo, K. B. & Park, E. C. Does the duration and time of sleep increase the risk of allergic rhinitis? Results of the 6-year nationwide Korea youth risk behavior web-based survey. PLOS ONE . 8 , e72507 (2013). Ng, D. K., Chan, C. H. & Ng, E. P. Natural history of snoring in Hong Kong adolescents. J. Paediatr. Child. Health . 50 , 596–604 (2014). Stuck, B. A. et al. Changes in daytime sleepiness, quality of life, and objective sleep patterns in seasonal allergic rhinitis: a controlled clinical trial. J. Allergy Clin. Immunol. 113 , 663–668 (2004). Ohashi-Doi, K., Lund, K., Mitobe, Y. & Okamiya, K. State of the art: development of a sublingual allergy immunotherapy tablet for allergic rhinitis in Japan. Biol. Pharm. Bull. 43 , 41–48 (2020). Novakova, S. M. et al. Quality of life improvement after a three-year course of sublingual immunotherapy in patients with house dust mite and grass pollen induced allergic rhinitis: results from real-life. Health Qual. Life Outcomes . 15 , 189 (2017). Roger, A. et al. Reduced work/academic performance and quality of life in patients with allergic rhinitis and impact of allergen immunotherapy. Allergy Asthma Clin. Immunol. 12 , 40 (2016). Kajiume, T. Sublingual immunotherapy for pediatric patients with mite allergies. Medicine . 101 , e28690 (2022). Members of the Yamanashi Adjunct Study of the Japan Environment and Children’s Study Group as. of 2023 4 : Zentaro Yamagata, Ryoji Shinohara, Sanae Otawa, Anna Kobayashi, Megumi Kushima, Hideki Yui, Takeshi Inukai, Kyoichiro Tsuchiya, Hirotaka Haro, Masanori Wako, Takahiko Mitsui, Kenji Kashiwagi, Daiju Sakurai, Koichiro Ueki, Sumire Ono, Yuka Akiyama, Tadao Ooka, Reiji Kojima, Hiroshi Yokomichi, Kunio Miyake, and Sayaka Horiuchi. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5060853","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":372027578,"identity":"1ee8a4ee-f0db-46a9-84c5-703dc65e2273","order_by":0,"name":"Daisuke Watanabe","email":"","orcid":"","institution":"University of Yamanashi","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Watanabe","suffix":""},{"id":372027581,"identity":"5afa3988-dc29-4acc-8ce1-7a6c5dc99f23","order_by":1,"name":"Sanae Otawa","email":"","orcid":"","institution":"University of Yamanashi","correspondingAuthor":false,"prefix":"","firstName":"Sanae","middleName":"","lastName":"Otawa","suffix":""},{"id":372027583,"identity":"cc77ceb3-9bf3-42e3-9185-ab6650ac4d2b","order_by":2,"name":"Megumi Kushima","email":"","orcid":"","institution":"University of Yamanashi","correspondingAuthor":false,"prefix":"","firstName":"Megumi","middleName":"","lastName":"Kushima","suffix":""},{"id":372027586,"identity":"650893a4-d611-4b9a-a86c-fd2aae226d51","order_by":3,"name":"Hideki Yui","email":"","orcid":"","institution":"University of Yamanashi","correspondingAuthor":false,"prefix":"","firstName":"Hideki","middleName":"","lastName":"Yui","suffix":""},{"id":372027587,"identity":"0e8d2686-7dcd-47b3-87a9-729b3e2e573f","order_by":4,"name":"Ryoji Shinohara","email":"","orcid":"","institution":"University of Yamanashi","correspondingAuthor":false,"prefix":"","firstName":"Ryoji","middleName":"","lastName":"Shinohara","suffix":""},{"id":372027589,"identity":"72a28ee4-8b71-4039-9214-bcfc00c4fc94","order_by":5,"name":"Zentaro Yamagata","email":"","orcid":"","institution":"University of Yamanashi","correspondingAuthor":false,"prefix":"","firstName":"Zentaro","middleName":"","lastName":"Yamagata","suffix":""},{"id":372027590,"identity":"ea9c8341-7c1b-4a62-bfcd-da34c43308e8","order_by":6,"name":"Daiju Sakurai","email":"","orcid":"","institution":"University of Yamanashi","correspondingAuthor":false,"prefix":"","firstName":"Daiju","middleName":"","lastName":"Sakurai","suffix":""},{"id":372027592,"identity":"c6122fb5-1a5b-414e-94d6-124039b16e5a","order_by":7,"name":"Kunio Miyake","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYBACCQbGBgaGAwxyMIEENjDFQ1iLMSlaQOAAQ2IDTAtBh0lOO9wm8eOMTfqG46cTPxfU1OXxMTA//MAgcwenFmnpxDbJnhtpuRvO5G6WnnHscDEbA5uxBAPPM5xa5IBaJHg+HM7dcCB3gzQP24HENgYGM6BfDuPVIvnnw/90g/NvN//m+VcH1ML+Da8WkMOkeW4cSDC4kbtNmreNGaiFB78tkrMTm61lziQbzrzxdps1b9/hxDZmnmKJBDx+kbid/vDmm2N28nznczff5vlWlzi/vX3jh489uEMMCFjAcaNwAMZnBuLEngM4VEOUfACR8g0ogj/wahkFo2AUjIKRBQBTmVpDVgsX7AAAAABJRU5ErkJggg==","orcid":"","institution":"University of Yamanashi","correspondingAuthor":true,"prefix":"","firstName":"Kunio","middleName":"","lastName":"Miyake","suffix":""}],"badges":[],"createdAt":"2024-09-10 01:31:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5060853/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5060853/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-83471-8","type":"published","date":"2024-12-30T15:57:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":69350676,"identity":"4e4c1625-6437-47fc-80e9-496dae632e7d","added_by":"auto","created_at":"2024-11-19 13:04:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":152820,"visible":true,"origin":"","legend":"\u003cp\u003eThe duration since the onset of symptoms (A), severity (B), and QOL (C) in children with perennial allergic rhinitis (PAR).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5060853/v1/dd90a71aa4322e230b413d14.png"},{"id":69350677,"identity":"fc5f22ae-4f65-4d2c-83ce-68813f268ad2","added_by":"auto","created_at":"2024-11-19 13:04:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":38666,"visible":true,"origin":"","legend":"\u003cp\u003eThe proportion of Japanese cedar pollen (JCP)-specific IgE class values by month of blood collection.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5060853/v1/938a9c95de76013ebf97a63e.png"},{"id":69350679,"identity":"9a8cb34e-9313-4135-baf4-1af0568a19b4","added_by":"auto","created_at":"2024-11-19 13:04:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":158307,"visible":true,"origin":"","legend":"\u003cp\u003eThe duration since the onset of symptoms (A), severity (B), and QOL (C) in children with seasonal allergic rhinitis (SAR).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5060853/v1/8ad9c052659de1b603dfb9d5.png"},{"id":73095333,"identity":"76a66bbd-6b40-4e7a-9243-d7667b4723c0","added_by":"auto","created_at":"2025-01-06 16:24:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":981032,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5060853/v1/c64e0b47-62ef-433d-b1c2-17e7aa571e70.pdf"},{"id":69352411,"identity":"9e66b016-8c7b-4f79-a306-ab931a734ba2","added_by":"auto","created_at":"2024-11-19 13:12:01","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":218372,"visible":true,"origin":"","legend":"","description":"","filename":"supplementalinfo.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5060853/v1/4a2b2b2713f5c5cbf72d2589.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association between allergen-specific immunoglobulin E positivity, allergic rhinitis symptoms, and quality of life in school-aged children","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAllergic rhinitis (AR) has been rapidly increasing worldwide, emerging as a significant health and social issue. In Denmark, AR prevalence among adults rose from 19\u0026ndash;32% over the past 30 years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. A recent meta-analysis reported an increase in AR prevalence among children from 8.39% during 2012\u0026ndash;2015 to 19.87% during 2016\u0026ndash;2022 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In Japan, Japanese cedar pollen (JCP) is the most common cause of AR, making it a national health concern. A survey of otolaryngologists and their families in Japan showed that JCP allergy prevalence increased from 16.2% in 1998 to 26.5% in 2008 and to 38.3% in 2019 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Furthermore, among children aged 5\u0026ndash;9 years, the prevalence of JCP allergy rose from 7.5% in 1998 to 30.1% in 2019, with the age of onset decreasing [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTraditionally, AR has been classified mainly into perennial AR (PAR) and seasonal AR (SAR) based on the exposure period [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. PAR is caused by indoor allergens, such as house dust mites (HDM), mold, and pet dander, leading to year-round symptoms. Conversely, SAR is triggered by outdoor allergens, such as cedar, cypress, and grass pollen, causing symptoms during specific seasons when pollen is dispersed. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines classify AR as intermittent and persistent. Intermittent AR involves symptoms for less than 4 days a week or fewer than 4 consecutive weeks, whereas persistent AR presents symptoms for more than 4 days per week and over 4 weeks. AR is characterized by sneezing, nasal congestion, nasal itching, and rhinorrhea, all triggered by an immunoglobulin E (IgE)-mediated response to inhaled allergens [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, diagnosing AR involves a medical interview and IgE antibody measurement to assess AR risk. Several European birth cohort studies have reported IgE levels for various allergens in children [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, in Japan, only one study has measured IgE levels for multiple allergens in children aged 5\u0026ndash;9 years living in Tokyo [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAR significantly impacts health-related quality of life (HRQOL). According to the ARIA recommendations, the severity of AR should be assessed by considering its impact on HRQOL [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. AR causes absenteeism from work and school, non-productive time, sleep disorders, and reduced participation in outdoor activities [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Additionally, children with AR may experience declines in learning ability and academic performance [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aimed to investigate the prevalence of HDM- and JCP-specific IgE positivity and its association with AR symptoms among schoolchildren in Yamanashi Prefecture, which has the highest prevalence of JCP allergy in Japan. Additionally, this study sought to assess the severity of symptoms and QOL in children with AR and to provide up-to-date descriptive epidemiological data.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eThe Japan Environment and Children\u0026rsquo;s Study (JECS) is a nationwide birth cohort study organized by the JECS Working Group to investigate environmental factors affecting children\u0026rsquo;s health and development. Pregnant women were recruited between January 2011 and March 2014 at 15 Regional Centers covering 19 prefectures across Japan, resulting in over 100,000 participants. We belong to the Koshin Regional Centers, which include Yamanashi and Nagano prefectures, and are responsible for conducting research on participants in Yamanashi Prefecture. Detailed protocols have been published previously [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBetween July 2019 and November 2022, we conducted an additional survey with participants in Yamanashi Prefecture when each child reached the age of 8 years. However, due to the impact of coronavirus disease 2019 (COVID-19), no surveys were conducted between March and June 2020. This additional survey included ophthalmological exams, oral examinations, and blood tests. In July 2023, a survey on AR symptoms was mailed to additional research participants, with responses obtained by April 2024. At the time of the survey, participants were aged 8\u0026ndash;12 years.\u003c/p\u003e \u003cp\u003eOf the 2,036 additional survey participants, 1,531 were eligible for analysis after excluding those for whom specific IgE measurements could not be obtained. Furthermore, after excluding participants who did not respond to the PAR and SAR questionnaires, the numbers were reduced to 1,229 and 1,196 individuals, respectively. To assess the severity of AR symptoms, individuals with symptoms of either PAR (n\u0026thinsp;=\u0026thinsp;345) or SAR (n\u0026thinsp;=\u0026thinsp;866) were selected from each group (Supplementary Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e The JECS protocol was reviewed and approved by the Ministry of the Environment\u0026rsquo;s Institutional Review Board for Epidemiological Studies and the Ethics Committees of all participating institutions (ethical approval number: 100910001). Additionally, this study was approved by the Institutional Review Board of Yamanashi University (No. 2070, 2218, and 2689). The study adhered to the principles of the Declaration of Helsinki, and informed consent was obtained from all subjects and/or their legal guardian(s).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of Total and allergen-specific IgE\u003c/h2\u003e \u003cp\u003eWe collected venous blood samples from 8-year-old children. Total IgE and allergen-specific IgE titers were measured using the ImmunoCAP system (SRL, Tokyo, Japan). Total IgE and specific IgE titers for HDM (\u003cem\u003eDer p\u003c/em\u003e 1) or JCP allergens were measured using the ImmunoCAP system (SRL, Tokyo, Japan). IgE levels for Dermatophagoides pteronyssinus (\u003cem\u003eDer p\u003c/em\u003e) and JCP allergens were classified into seven categories: class 0 (\u0026lt;\u0026thinsp;0.35 UA/mL), class 1 (0.35\u0026ndash;0.69 UA/mL), class 2 (0.70\u0026ndash;3.49 UA/mL), class 3 (3.5\u0026ndash;17.49 UA/mL), class 4 (17.5\u0026ndash;49.99 UA/mL), class 5 (50\u0026ndash;99.99 UA/mL), and class 6 (\u0026ge;\u0026thinsp;100 UA/mL). Positive IgE sensitization to allergens was defined as class 2 or higher.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eInvestigation of AR symptoms\u003c/h2\u003e \u003cp\u003eData on AR symptoms during school age were collected using a self-administered questionnaire completed by the mothers. They were asked to indicate whether the child currently had PAR (caused by dust mites, house dust, etc., resulting in year-round nasal or eye symptoms) and/or SAR (caused mainly by pollen, resulting in nasal or eye symptoms during specific seasons, commonly known as hay fever) by selecting one of the following options: \"Diagnosed at a hospital and receiving treatment,\" \"Diagnosed by a hospital, but not treated,\" \"Symptomatic but has not seen a doctor,\" \"No symptoms,\" or \"Undecided.\" For mothers reporting that their child had symptoms of either type of AR, additional questions were asked to assess the severity of the child's AR and its impact on their QOL.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of the severity and quality of life (QOL) in PAR\u003c/h2\u003e \u003cp\u003eMothers were asked to indicate how many years had passed since their child was first diagnosed with PAR or began experiencing nasal or eye symptoms by choosing from the following options: \"Less than 6 months,\" \"6 months to less than 1 year,\" \"1 year to less than 2 years,\" \"2 years to less than 3 years,\" \"3 years to less than 4 years,\" \"4 years to less than 5 years,\" \"5 years to less than 10 years,\" and \"10 years or more.\" Mothers were asked the following question: \"How often does your child experience sneezing and nose blowing on an average day? Please provide an approximate number of times per day based on recent observations.\" The response options were: \"Almost never,\" \"1\u0026ndash;5 times,\" \"6\u0026ndash;10 times,\" \"11\u0026ndash;20 times,\" and \"More than 21 times.\" Additionally, regarding nasal congestion, mothers were asked: \"How often does your child experience nasal congestion? Please describe the recent situation.\" The response options were: \"Almost never,\" \"Some nasal congestion, but no mouth breathing (can breathe through the nose),\" \"Severe nasal congestion, occasional mouth breathing (cannot always breathe through the nose),\" \"Very severe nasal congestion, frequent mouth breathing (mostly breathes through the mouth),\" and \"Completely congested all day.\" The severity of AR symptoms was classified based on the Nasal Allergy Guidelines of the Japan Society of Immunology Allergology and Infection in Otorhinolaryngology, categorizing them as none, mild, moderate, severe, and severest. To evaluate the impact on daily life, mothers were asked: \"How much do your child's nasal or eye symptoms affect their daily life (studying, outdoor activities, or sleep)?\" The response options were: \"None,\" \"Slightly,\" \"Significantly,\" and \"Impossible.\"\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of the severity and quality of life (QOL) in SAR\u003c/h2\u003e \u003cp\u003eMothers were asked to indicate how many years had passed since their child was first diagnosed with hay fever or began experiencing nasal or eye symptoms, using the same options provided for PAR. Additionally, mothers were asked to indicate all the months during which their child experienced hay fever symptoms throughout the year. During the period when symptoms occurred, mothers were also asked to provide responses regarding sneezing attacks, frequency of nose blowing, and the condition of nasal congestion, using the same options provided for PAR symptoms, and severity classification was conducted. Additionally, mothers were asked about the impact of nasal or eye symptoms on their child's studying, outdoor activities, and sleep, using the same options provided for PAR symptoms.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eThe sex of the children was extracted from the medical records of the dataset jecs-ta-20190930-qsn, released in October 2019 and finalized in March 2022. Sex was cross-tabulated with allergen-specific IgE or nasal symptoms, and the relationship was evaluated using the chi-square test. The Mann-Whitney U test was used to compare nonspecific IgE levels according to sex. Statistical significance was set at a p-value of 0.05 (two-sided). All statistical analyses were conducted using Statistical Package for the Social Sciences software version 27.0 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the cross-tabulation by sex for HDM-specific IgE sensitization and PAR symptoms. A total of 656 (53.4%) children were positive for HDM-specific IgE sensitization, including 362 (60.6%) boys and 294 (46.5%) girls. A comparison of the median levels of nonspecific IgE showed that boys had higher nonspecific IgE levels than girls. For PAR symptoms, 345 (28.1%) children had symptoms overall, with 194 (32.5%) boys and 151 (23.9%) girls. Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e shows the cross-tabulation of HDM-specific IgE sensitization and PAR symptoms: 69 (12.0%) children who tested negative for HDM-specific IgE had PAR symptoms, whereas 380 (57.9%) children with positive HDM-specific IgE showed no PAR symptoms.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of house dust mite (HDM)-specific IgE and perennial allergic rhinitis symptoms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003e1,229 (100)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBoys\u003c/p\u003e \u003cp\u003e597 (48.6)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGirls\u003c/p\u003e \u003cp\u003e632 (51.4)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHDM-specific IgE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e573 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e235 (39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e338 (53.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e656 (53.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e362 (60.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e294 (46.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e523 (42.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e210 (35.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e313 (49.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50 (4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e123 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e165 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e85 (14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e179 (14.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e102 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e77 (12.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e128 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e79 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e61 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-specific IgE (IU/mL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e181.0\u003c/p\u003e \u003cp\u003e(55.6\u0026ndash;471.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e235.0\u003c/p\u003e \u003cp\u003e(77.9\u0026ndash;603.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e135.0\u003c/p\u003e \u003cp\u003e(46.1\u0026ndash;365.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptoms of perennial allergic rhinitis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e766 (62.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e356 (59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e410 (64.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndecided\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e118 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e71 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosed at a hospital and receiving treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e186 (15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e108 (18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e78 (12.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosed by a hospital, but not treated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic but has not seen a doctor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e67 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e34 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003en (%) or median (IQR).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ep-values were obtained from the chi-square test or Mann-Whitney U test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the duration and severity of PAR symptoms along with their impact on QOL. The most common duration of PAR symptoms was 5\u0026ndash;10 years, affecting 39.1% of the children (38.1% of boys and 40.4% of girls), with no significant sex differences. Symptom severity was classified as follows: no symptoms (16.5%), mild (40.9%), moderate (24.1%), severe (11.6%), and very severe (2.6%), with no sex differences in severity. The impact of PAR symptoms on studying, outdoor activities, and sleep was: 67.2%, 70.7%, and 60.9% experienced no impact; 27.8%, 25.2%, and 33.0% experienced a slight impact; and 3.2%, 2.3%, and 3.8% experienced a considerable impact, respectively. No significant differences were observed between boys and girls regarding QOL impacts.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the cross-tabulation by sex for JCP-specific IgE sensitization and SAR symptoms. A total of 820 (68.2%) children were positive for JCP-specific IgE sensitization, including 430 (73.1%) boys and 390 (64.1%) girls. Supplementary Table S2 details the cross-tabulation of JCP-specific IgE sensitization and SAR symptoms: 166 (44.1%) children negative for JCP-specific IgE had SAR symptoms, whereas 120 (14.6%) children positive for JCP-specific IgE showed no SAR symptoms. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the proportion of JCP-specific IgE class levels by month of blood sampling, with June showing the highest sensitization proportion (79.6%) and August the lowest (58.7%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of Japanese cedar pollen (JCP)-specific IgE and seasonal allergic rhinitis symptoms\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003e1,196 (100)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBoys\u003c/p\u003e \u003cp\u003e588 (49.2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGirls\u003c/p\u003e \u003cp\u003e608 (50.8)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eJCP-specific IgE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e376 (31.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e158 (26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e218 (35.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e820 (68.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e430 (73.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e390 (64.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e333 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e141 (24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e192 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e26 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e131 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e65 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e241(20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e113 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e128 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e227 (19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e131 (22.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e96 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e137 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e71 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66 (10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClass 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e84 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e35 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-specific IgE (IU/mL)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e182.0\u003c/p\u003e \u003cp\u003e(57.5\u0026ndash;472.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e239.0\u003c/p\u003e \u003cp\u003e(80.8\u0026ndash;609.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e135.0\u003c/p\u003e \u003cp\u003e(46.2\u0026ndash;354.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptoms of seasonal allergic rhinitis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e280 (23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e133 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e147 (24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndecided\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e50 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28 (4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosed at a hospital and receiving treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e508 (50.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e311 (52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e297 (48.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosed by a hospital, but not treated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e143 (12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e78 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e65 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic but has not seen a doctor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e115 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e71 (11.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003en (%) or median (IQR).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ep-values were obtained from the chi-square test or Mann-Whitney U test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the duration and severity of SAR symptoms along with their impact on QOL. The most common duration of SAR symptoms was 5\u0026ndash;10 years, affecting 35.7% of the children (36.5% of boys and 34.9% of girls), with no significant sex differences. Symptom severity was classified as follows: no symptoms (3.0%), mild (17.1%), moderate (31.3%), severe (29.9%), and very severe (15.0%), with no sex differences in severity. The impact of SAR symptoms on studying, outdoor activities, and sleep was: 39.8%, 41.5%, and 39.0% experienced no impact; 51.0%, 46.7%, and 49.5% experienced a slight impact; 8.9%, 11.7%, and 11.1% experienced a considerable impact; and 0.1%, 0.1%, and 0.2% experienced an impossible impact.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the number of children with IgE polysensitization to HDM and JCP. Moreover, 367 (23.8%) children were HDM(-)JCP(-), 119 (7.7%) were HDM(+)JCP(-), 336 (21.8%) were HDM(-)JCP(+), and 717 (46.6%) were HDM(+)JCP(+). The proportion of IgE polysensitization to HDM and JCP was higher in boys than in girls.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCo-sensitization to house dust mite (HDM)- and Japanese cedar pollen (JCP)-specific IgE\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003e1,539 (100)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBoys\u003c/p\u003e \u003cp\u003e769 (50.0)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGirls\u003c/p\u003e \u003cp\u003e770 (50.0)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDM (-) JCP (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e367 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e138 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e229 (29.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDM (+) JCP (-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e119 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDM (-) JCP (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e336 (21.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e157 (20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e179 (23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDM (+) JCP (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e717 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e407 (52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e310 (40.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ep-values were obtained from the chi-square test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study represented the first investigation of HDM-specific and JCP-specific IgE along with AR symptoms in healthy school-age children. Among 8-year-olds in the study area, 68.2% were sensitized to JCP-specific IgE, with a higher prevalence in boys compared to girls. Furthermore, children with SAR exhibited more severe rhinitis and greater impacts on their QOL concerning studying, outdoor activities, and sleep compared to those with PAR.\u003c/p\u003e \u003cp\u003eTypically, blood IgE levels are measured when patients with suspected allergies visit hospitals. However, due to challenges in accurately assessing symptoms and reluctance to undergo blood sampling, opportunities to obtain blood samples from children are limited. Consequently, reports on the prevalence of IgE sensitization in the general population are scarce. A meta-analysis of five European birth cohorts reported that 25\u0026ndash; 45% of 8\u0026ndash;10-year-olds are sensitized to inhalant allergens [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. A French cohort study reported that approximately 20% of 8\u0026ndash;9-year-olds have HDM-specific IgE sensitization [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In a prospective birth cohort study of the general population, called the Tokyo Children\u0026rsquo;s Health, Illness and Development study (T-Child study), the percentage of 9-year-olds sensitized to \u003cem\u003eDer f\u003c/em\u003e 1-specific IgE is 54.3% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], a figure comparable to our study\u0026rsquo;s result of 53.4%. The hot and humid climate in Japan, which facilitates mites proliferation, likely contributes to higher rates of IgE sensitization to mites compared to Europe and America [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn Japan, cedar and cypress are the most common pollen allergy-causing plants. Cedar pollen allergen \u003cem\u003eCry j\u003c/em\u003e 1 cross-reacts with cypress pollen allergen \u003cem\u003eCha o\u003c/em\u003e 1, leading many individuals with cedar pollen allergies to also react to cypress pollen [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In the T-Child study, the percentage of 9-year-olds sensitized to JCP-specific IgE is 57.8%, which is lower than the 68.6% found in our study [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This difference could be due to regional differences, as the Yamanashi Prefecture, where our study was conducted, is surrounded by forests with high levels of cedar and cypress pollen. A 2019 nationwide survey identified Yamanashi Prefecture as having the highest prevalence of JCP allergy in Japan [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The JECS study, which surveyed approximately 88,000 pregnant women across Japan, found a national average sensitization rate to JCP-specific IgE of 50.9%. In contrast, the Koshin region, including Yamanashi and Nagano Prefectures, showed the highest rate at 67.0% [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. By the age of 8 years, the proportion of children with JCP-specific IgE sensitization was already comparable to that of adults.\u003c/p\u003e \u003cp\u003eMost previous studies have measured JCP-specific IgE during the pollen dispersal period. In this study, blood samples were collected around the participants' 8th birthday between July 2019 and November 2022, measuring allergen-specific IgE levels. A distinctive aspect of our study was the measurement of JCP-specific IgE both during and outside the cedar pollen season, which may have led to an underestimation of the JCP-specific IgE sensitization positivity rate. The JCP dispersal period is from February to April when pollen levels peak. According to the survey results for the period when pollen allergy symptoms appeared (Supplementary Figure S2), cedar and cypress pollen were the causes, as most patients with pollen allergy exhibited symptoms from February to May. In contrast, approximately 30% of patients exhibited symptoms between September and November, suggesting ragweed and mugwort pollen as possible triggers. The positivity rate for JCP-specific IgE increased from September to November (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), possibly due to \"crazy blooming,\" where warm autumns lead to out-of-season flowering [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], leading to JCP exposure even in the fall. Additionally, approximately 60% of children tested positive for JCP-specific IgE sensitization even during the non-dispersal period, suggesting persistent high IgE levels throughout the year.\u003c/p\u003e \u003cp\u003eMeta-analyses have shown sex differences in the prevalence of AR, with rates in males during childhood and in females during adolescence [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. A survey of a healthy population aged 20\u0026ndash;59 years living in Tokyo, Japan [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], found a 38.3% overall sensitization rate to HDM-specific IgE (\u0026ge;\u0026thinsp;0.35 UA/mL), with males showing a significantly higher rate than females. The overall sensitization rate to JCP-specific IgE was 66.8%, with no significant sex differences across age groups, though males aged 20\u0026ndash; 29 had a notably higher rate than females. These findings align with our results, showing that 8-year-old boys had higher sensitization rates for both HDM-specific IgE (odd s ratio [OR]: 1.77, 95% confidence interval [CI]: 1.41\u0026ndash;2.22) and JCP-specific IgE (OR: 1.52, 95% CI: 1.19\u0026ndash;1.95) compared to girls. Additionally, we uniquely revealed that boys had a higher proportion of polysensitization to both HDM-specific and JCP-specific IgEs, whereas girls had a higher proportion of sensitization exclusively to JCP-specific IgE.\u003c/p\u003e \u003cp\u003eSAR is typically associated with more acute and severe symptoms than PAR due to high pollen exposure over a short period. Our study found that 85.4% of children with JCP-specific IgE sensitization had AR symptoms, whereas only 42.1% of those sensitized to HDM-specific IgE had such symptoms, indicating a significant difference between sensitization and the presence of symptoms. Furthermore, among children with AR, 76.2% of those with SAR had moderate to severe symptoms, compared to 38.3% of those with PAR. In a survey conducted in 2017 targeting patients with AR, the proportion of moderate or severe cases among those aged 15\u0026ndash;19 years is 63.0% for PAR and 61.6% for SAR [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In comparison, our study revealed lower severity for PAR, potentially due to an underestimation of PAR severity relative to SAR in children with both conditions.\u003c/p\u003e \u003cp\u003eThe main symptoms of AR, including sneezing, nasal itching, rhinorrhea, and nasal congestion [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], are associated with sleep deprivation [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], fatigue [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], and mental health issues [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] in patients with AR. The relationship between AR and sleep disturbances is well-documented in adolescents, with AR children experiencing shorter nighttime sleep duration [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and increased daytime sleepiness [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Moreover, as rhinitis severity increases, academic performance often declines due to reduced classroom productivity [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Our results indicated that approximately 75% of children with pollen allergies experienced moderate to severe AR symptoms, with approximately 60% affected in their sleep, outdoor activities, and studying, highlighting a serious issue. However, appropriate interventions for AR may improve both the severity of AR and QOL. In particular, allergen-specific immunotherapy (AIT) improves AR symptoms, QOL, and performance at work/school [\u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Sublingual immunotherapy (SLIT), a type of AIT, has rapidly gained acceptance in recent years owing to its minimal adverse effects and convenient administration. In Japan, the starting age for SLIT was lowered to 5 years old in 2018 [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], making it a viable option for improving QOL and academic outcomes in children, provided safe long-term adherence to medication is ensured.\u003c/p\u003e \u003cp\u003eThe strength of this study lies in its investigation of the relationship between allergen-specific IgE sensitization and AR symptoms among elementary school students in the region with the highest prevalence of hay fever in Japan. Additionally, this study elucidated the severity of AR and its impact on the QOL among patients with AR. Opportunities to collect blood samples from typically healthy 8-year-old children are limited, making the measurement of IgE levels and the calculation of sensitization rates in this age group a valuable data resource. Nevertheless, this study had some limitations. Firstly, the diagnosis and symptoms of AR relied on self-reported questionnaires completed by mothers, which could have led to potential misclassification. Secondly, blood samples were collected when the children were 8 years old, whereas the symptom questionnaires were completed when the children were between 8 and 12 years old, raising the possibility that some children who developed AR symptoms after the age of 8 were included. However, considering the results regarding symptom duration, most children likely experienced rhinitis symptoms before the age of 8 years. Thirdly, although we investigated the impact of AR on children's QOL regarding studying, outdoor activities, and sleep, the external validity of the questions remained uncertain. The Japanese Rhinitis Quality of Life Questionnaire (JRQLQ No1), commonly used for assessing QOL in AR, was not utilized in this study because it is designed for patients visiting medical institutions and is not suitable for evaluating healthy school-age children. Finally, although some AR symptoms could have been triggered by unmeasured allergens, approximately 85% of children with SAR symptoms reported experiencing them in March and April, suggesting that most children with SAR were likely sensitized to pollen allergens such as cedar and cypress.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study revealed the prevalence of sensitization to HDM- and JCP-specific IgE and the current state of AR symptoms among 8-year-old children in the region with the highest number of patients with hay fever in Japan. Children with cedar pollen allergies experienced significant negative impacts on sleep and academic performance, making early prevention and treatment from infancy essential. Further follow-up studies from school age onwards are necessary to elucidate the effects of treatment on symptoms and QOL.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research received support from a Grant-in-Aid for Scientific Research conferred by the Japanese Ministry of Education, Culture, Sports, Science, and Technology (No. 20H03928, 24K13437) and TERUMO LIFE SCIENCE FOUNDATION (23-Ⅲ5024). The JECS was funded by the Ministry of the Environment, Japan. The findings and conclusions of this study are solely the responsibility of the authors and do not represent the official views of the above-mentioned government.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eKM conceived the study design. DW and KM performed statistical analysis and drafted the initial manuscript. DW, KM, SO, MK, HY, RS, and ZY collected the data. DW, KM, SO, MK, HY, RS, ZY, DW, DS and the JECS critically reviewed and revised the manuscript. All authors have approved the final manuscript as submitted and agree to be accountable for all aspects of this work.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe express our gratitude to every participant in the JECS and appreciate the contributions of all individuals engaged in data collection. We would like to thank Keiko Mitsui and Ayumi Okada for their technical support in data collection and cleaning. We would like to thank Editage (www.editage.jp) for English language editing.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData are unsuitable for public deposition due to ethical restrictions and legal framework of Japan. It is prohibited by the Act on the Protection of Personal Information (Act No. 57 of 30 May 2003, amendment on 9 September 2015) to publicly deposit the data containing personal information. Ethical Guidelines for Epidemiological Research enforced by the Japan Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare also restrict the open sharing of the epidemiologic data. All inquiries about access to data should be sent to: [email protected]. The person responsible for handling enquiries sent to this e-mail address is Dr Shoji F. Nakayama, JECS Programme Office, National Institute for Environmental Studies.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLeth-M\u0026oslash;ller, K. B., Skaaby, T. \u0026amp; Linneberg, A. Allergic rhinitis and allergic sensitisation are still increasing among Danish adults. \u003cem\u003eAllergy\u003c/em\u003e. \u003cb\u003e75\u003c/b\u003e, 660\u0026ndash;668 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLicari, A. et al. Epidemiology of allergic rhinitis in children: A systematic review and meta-analysis. \u003cem\u003eJ. Allergy Clin. Immunol. Pract.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e, 2547\u0026ndash;2556 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatsubara, A. et al. Epidemiological survey of allergic rhinitis in Japan 2019. \u003cem\u003eNippon Jibiinkoka Gakkai Kaiho\u003c/em\u003e 123, 485\u0026thinsp;\u0026ndash;\u0026thinsp;90 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng, Y., Wang, C. \u0026amp; Zhang, L. Advances and novel developments in allergic rhinitis. \u003cem\u003eAllergy\u003c/em\u003e. \u003cb\u003e75\u003c/b\u003e, 3069\u0026ndash;3076 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBousquet, J. et al. Allergic rhinitis. \u003cem\u003eNat. Rev. Dis. Primers\u003c/em\u003e. \u003cb\u003e6\u003c/b\u003e, 95 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGruzieva, O. et al. Meta-analysis of air pollution exposure association with allergic sensitization in European birth cohorts. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cb\u003e133\u003c/b\u003e, 767\u0026ndash;776 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGabet, S. et al. Asthma and allergic rhinitis risk depends on house dust mite specific IgE levels in Paris birth cohort children. \u003cem\u003eWorld Allergy Organ. J.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e, 100057 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto-Hanada, K. et al. IgE responses to multiple allergen components among school-aged children in a general population birth cohort in Tokyo. \u003cem\u003eWorld Allergy Organ. J.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e, 100105 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBousquet, J. et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). \u003cem\u003eAllergy\u003c/em\u003e 63 Supplement 86, 8-160 (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVandenplas, O. et al. Impact of rhinitis on work productivity: a systematic review. \u003cem\u003eJ. Allergy Clin. Immunol. Pract.\u003c/em\u003e \u003cb\u003e6\u003c/b\u003e, 1274\u0026ndash;1286e9 (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevillier, P. et al. In allergic rhinitis, work, classroom and activity impairments are weakly related to other outcome measures. \u003cem\u003eClin. Exp. Allergy\u003c/em\u003e. \u003cb\u003e46\u003c/b\u003e, 1456\u0026ndash;1464 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePagel, J. M. L. \u0026amp; Mattos, J. L. Allergic rhinitis and its effect on sleep. \u003cem\u003eOtolaryngol. Clin. North. Am.\u003c/em\u003e \u003cb\u003e57\u003c/b\u003e, 319\u0026ndash;328 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalker, S. et al. Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case\u0026ndash;control study. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cb\u003e120\u003c/b\u003e, 381\u0026ndash;387 (2007).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlaiss, M. S., Hammerby, E., Robinson, S., Kennedy-Martin, T. \u0026amp; Buchs, S. The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review. \u003cem\u003eAnn. Allergy Asthma Immunol.\u003c/em\u003e \u003cb\u003e121\u003c/b\u003e, 43\u0026ndash;52e3 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawamoto, T. et al. Rationale and study design of the Japan environment and children's study (JECS). \u003cem\u003eBMC Public. Health\u003c/em\u003e. \u003cb\u003e14\u003c/b\u003e, 25 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichikawa, T. et al. Baseline profile of participants in the Japan Environment and Children's Study (JECS). \u003cem\u003eJ. Epidemiol.\u003c/em\u003e \u003cb\u003e28\u003c/b\u003e, 99\u0026ndash;104 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFukutomi, Y., Yasueda, H., Nakazawa, T., Taniguchi, M. \u0026amp; Akiyama, K. Indoor mite and insect allergens and allergic disease. \u003cem\u003eIndoor Environ.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e, 87\u0026ndash;96 (2009).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSone, T. et al. Identification of human T cell epitopes in Japanese cypress pollen allergen, Cha o 1, elucidates the intrinsic mechanism of cross-allergenicity between Cha o 1 and Cry j 1, the major allergen of Japanese cedar pollen, at the T cell level. \u003cem\u003eClin. Exp. Allergy\u003c/em\u003e. \u003cb\u003e35\u003c/b\u003e, 664\u0026ndash;671 (2005).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto-Hanada, K. et al. Allergic profiles of mothers and fathers in the Japan Environment and Children's Study (JECS): a nationwide birth cohort study. \u003cem\u003eWorld Allergy Organ. J.\u003c/em\u003e \u003cb\u003e10\u003c/b\u003e, 24 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakahashi, Y. Current state of Japanese cedar (Cryptomeria japonica D. Don) pollen information and future directions for its airborne allergen determination and improved pollen monitoring. \u003cem\u003eAerobiology\u003c/em\u003e. \u003cb\u003e2\u003c/b\u003e, 1\u0026ndash;17 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaira, H., Yoshii, E. \u0026amp; Teranishi, H. The Characteristic of the pollen dispersal of cryptomeria japonica. \u003cem\u003eArerugi\u003c/em\u003e. \u003cb\u003e53\u003c/b\u003e, 1187\u0026ndash;1194 (2004).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFr\u0026ouml;hlich, M. et al. Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from childhood to adulthood? A meta-analysis. \u003cem\u003eClin. Transl Allergy\u003c/em\u003e. \u003cb\u003e7\u003c/b\u003e, 44 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka, J. et al. Prevalence of inhaled allergen-specific IgE antibody positivity in the healthy Japanese population. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cb\u003e133\u003c/b\u003e, 632\u0026ndash;9e5 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkamoto, Y., Ohta, T., Karim, Y., Kaneko, Y. \u0026amp; Yoden, T. Survey of patient awareness and actions for improved quality of life in perennial allergic rhinitis. \u003cem\u003eTher. Res.\u003c/em\u003e \u003cb\u003e38\u003c/b\u003e, 1001\u0026ndash;1037 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkubo, K. et al. Japanese guidelines for allergic rhinitis 2020. \u003cem\u003eAllergol. Int.\u003c/em\u003e 69, 331\u0026thinsp;\u0026ndash;\u0026thinsp;45 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu, J., Zhang, X., Zhao, Y. \u0026amp; Wang, Y. The association between allergic rhinitis and sleep: A systematic review and meta-analysis of observational studies. \u003cem\u003ePLOS ONE\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e, e0228533 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim, O., Kim, B., Jeong, H., Lee, J. \u0026amp; Jung, H. Sleep, fatigue, and depressive symptoms among female nurses with allergic rhinitis. \u003cem\u003eHealthc. (Basel)\u003c/em\u003e. \u003cb\u003e9\u003c/b\u003e, 1328 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmritwar, A. U. et al. Mental health in allergic rhinitis: depression and suicidal behavior. \u003cem\u003eCurr. Treat. Options Allergy\u003c/em\u003e. \u003cb\u003e4\u003c/b\u003e, 71\u0026ndash;97 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwon, J. A., Lee, M., Yoo, K. B. \u0026amp; Park, E. C. Does the duration and time of sleep increase the risk of allergic rhinitis? Results of the 6-year nationwide Korea youth risk behavior web-based survey. \u003cem\u003ePLOS ONE\u003c/em\u003e. \u003cb\u003e8\u003c/b\u003e, e72507 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNg, D. K., Chan, C. H. \u0026amp; Ng, E. P. Natural history of snoring in Hong Kong adolescents. \u003cem\u003eJ. Paediatr. Child. Health\u003c/em\u003e. \u003cb\u003e50\u003c/b\u003e, 596\u0026ndash;604 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStuck, B. A. et al. Changes in daytime sleepiness, quality of life, and objective sleep patterns in seasonal allergic rhinitis: a controlled clinical trial. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cb\u003e113\u003c/b\u003e, 663\u0026ndash;668 (2004).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOhashi-Doi, K., Lund, K., Mitobe, Y. \u0026amp; Okamiya, K. State of the art: development of a sublingual allergy immunotherapy tablet for allergic rhinitis in Japan. \u003cem\u003eBiol. Pharm. Bull.\u003c/em\u003e \u003cb\u003e43\u003c/b\u003e, 41\u0026ndash;48 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNovakova, S. M. et al. Quality of life improvement after a three-year course of sublingual immunotherapy in patients with house dust mite and grass pollen induced allergic rhinitis: results from real-life. \u003cem\u003eHealth Qual. Life Outcomes\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e, 189 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoger, A. et al. Reduced work/academic performance and quality of life in patients with allergic rhinitis and impact of allergen immunotherapy. \u003cem\u003eAllergy Asthma Clin. Immunol.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e, 40 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKajiume, T. Sublingual immunotherapy for pediatric patients with mite allergies. \u003cem\u003eMedicine\u003c/em\u003e. \u003cb\u003e101\u003c/b\u003e, e28690 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMembers of the Yamanashi Adjunct Study of the Japan Environment and Children\u0026rsquo;s Study Group as. of 2023\u003csup\u003e4\u003c/sup\u003e: Zentaro Yamagata, Ryoji Shinohara, Sanae Otawa, Anna Kobayashi, Megumi Kushima, Hideki Yui, Takeshi Inukai, Kyoichiro Tsuchiya, Hirotaka Haro, Masanori Wako, Takahiko Mitsui, Kenji Kashiwagi, Daiju Sakurai, Koichiro Ueki, Sumire Ono, Yuka Akiyama, Tadao Ooka, Reiji Kojima, Hiroshi Yokomichi, Kunio Miyake, and Sayaka Horiuchi.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Allergic Rhinitis, Quality of Life, School-aged Children, Seasonal allergic rhinitis (SAR), Severity, Specific IgE Antibodies","lastPublishedDoi":"10.21203/rs.3.rs-5060853/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5060853/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aimed to investigate the relationship between allergen-specific immunoglobulin E (IgE) sensitization and allergic rhinitis (AR) symptoms in school-aged children in Japan and to understand the current severity of AR symptoms and the quality of life (QOL) among children with AR. We analyzed data from 8-year-old children who participated in the Yamanashi Adjunct Study of the Japan Environment and Children's Study, focusing on those with complete information o on specific IgE levels and AR (1,229 for perennial AR [PAR] and 1,196 for seasonal AR [SAR]). Sensitization was determined when allergen-specific IgE levels were class 2 (0.70 U/mL) or higher. Among those who tested positive for house dust mite (HDM)-specific IgE, 656 (53.4%) children were identified, including 362 (60.6%) boys and 294 (46.5%) girls. For Japanese cedar pollen (JCP)-specific IgE, 820 (68.6%) children were sensitized, with 430 (73.1%) boys and 390 (64.1%) girls. Among children with AR, 38.3% of those with PAR and 76.2% of those with SAR experienced moderate to severe nasal symptoms. This study highlighted the high prevalence of JCP-specific IgE sensitization among school-aged children in Japan and provided insights into the severity of AR symptoms and the impact on QOL in these children.\u003c/p\u003e","manuscriptTitle":"Association between allergen-specific immunoglobulin E positivity, allergic rhinitis symptoms, and quality of life in school-aged children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-19 13:03:56","doi":"10.21203/rs.3.rs-5060853/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-30T04:42:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-22T08:45:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-19T09:07:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"51032492918486869335931015562849845117","date":"2024-10-16T23:45:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164090754544852653299528128294494196207","date":"2024-10-10T02:37:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-09T14:33:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-07T14:04:35+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-09-23T08:07:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-21T11:12:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-09-10T01:29:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"97bb70df-5d20-4427-913b-bcb19e16a1ea","owner":[],"postedDate":"November 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":39592461,"name":"Health sciences/Medical research/Epidemiology"},{"id":39592462,"name":"Health sciences/Health care/Public health/Epidemiology"}],"tags":[],"updatedAt":"2025-01-06T16:24:09+00:00","versionOfRecord":{"articleIdentity":"rs-5060853","link":"https://doi.org/10.1038/s41598-024-83471-8","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-12-30 15:57:45","publishedOnDateReadable":"December 30th, 2024"},"versionCreatedAt":"2024-11-19 13:03:56","video":"","vorDoi":"10.1038/s41598-024-83471-8","vorDoiUrl":"https://doi.org/10.1038/s41598-024-83471-8","workflowStages":[]},"version":"v1","identity":"rs-5060853","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5060853","identity":"rs-5060853","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}