Allergic rhinitis phenotypes with distinct transcriptome profiles in children: A birth cohort.

BACKGROUND: Allergic rhinitis (AR) phenotypes in childhood are unclear. OBJECTIVES: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics. METHODS: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype. RESULTS: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response. CONCLUSIONS: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.

Frequency of exacerbation and degree of required asthma medication can characterize childhood longitudinal asthma trajectories.

BACKGROUND: To the best of our knowledge, there have been no investigations of longitudinal asthma trajectories based on asthma exacerbation frequency and medications required for asthma control in children. OBJECTIVE: To investigate longitudinal asthma trajectories based on the exacerbation frequency throughout childhood and asthma medication ranks. METHODS: A total of 531 children aged 7 to 10 years were enrolled from the Korean childhood Asthma Study. Required asthma medications for control of asthma from 6 to 12 years of age and asthma exacerbation frequency from birth to 12 years of age were obtained from the Korean National Health Insurance System database. Longitudinal asthma trajectories were identified on the basis of asthma exacerbation frequency and asthma medication ranks. RESULTS: Four asthma clusters were identified: lesser exacerbation with low-step treatment (8.1%), lesser exacerbations with middle-step treatment (30.7%), highly frequent exacerbations in early childhood with small-airway dysfunction (5.7%), and frequent exacerbations with high-step treatment (55.6%). The frequent exacerbations with high-step treatment cluster were characterized by a high prevalence of male sex, increased blood eosinophil (counts) with fractional exhaled nitric oxide, and high prevalence of comorbidities. The highly frequent exacerbation in early childhood with small-airway dysfunction cluster was characterized by recurrent wheeze in preschool age, with high prevalence of acute bronchiolitis in infancy and a greater number of family members with small-airway dysfunction at school age. CONCLUSION: The present study identified 4 longitudinal asthma trajectories on the basis of the frequency of asthma exacerbation and asthma medication ranks. These results would help clarify the heterogeneities and pathophysiologies of childhood asthma.

Fetal growth rather than prematurity determines lung function in children with asthma.

BACKGROUND AND OBJECTIVE: Preterm birth or fetal growth has been associated with reduced lung function and asthma during childhood in the general population. We aimed to elucidate whether prematurity or fetal growth has a significant influence on lung function or symptoms in children with stable asthma. METHODS: We included children with stable asthma who participated in the Korean childhood Asthma Study cohort. Asthma symptoms were determined by asthma control test (ACT). Percent predicted values of pre- and post-bronchodilator (BD) lung function including forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), and forced expiratory flow at 25%-75% of FVC (FEF25%-75% ) were measured. Lung function and symptoms were compared according to the history of preterm birth and birth weight (BW) for gestational age (GA). RESULTS: The study population consisted of 566 children (age range: 5-18 years). There were no significant differences in lung function and ACT between preterm and term subjects. We observed no significant difference in ACT but significant differences were observed in pre- and post-BD FEV1 , pre- and post-BD FVC, and post-BD FEF25%-75% according to BW for GA in total subjects. Two-way ANOVA revealed that BW for GA rather than prematurity was a significant determining factor for pre- and post-BD lung function. After regression analysis, BW for GA was still a significant determining factor of pre- and post-BD FEV1 and pre- and post-BD FEF25%-75% . CONCLUSION: Fetal growth rather than prematurity appears to have a significant effect on lung function in children with stable asthma.

Particulate matter exposure during pregnancy increases risk of childhood asthma: modified by gender and NRF2 genotype.

BACKGROUND: Exposure to particulate matter (PM) has been known to develop asthma in children and the oxidative stress-related mechanisms are suggested. For the development of asthma, not only the exposure dose but also the critical window and the risk modifying factors should be evaluated. OBJECTIVE: We investigated whether prenatal exposure to PM10 increases the risk of childhood asthma and evaluated the modifying factors, such as gender and reactive oxidative stress-related gene. METHODS: A general population-based birth cohort, the Panel Study of Korean Children (PSKC), including 1572 mother-baby dyads was analyzed. Children were defined to have asthma at age 7 when a parent reported physician-diagnosed asthma. Exposure to PM10 during pregnancy was estimated by land-use regression models based on national monitoring system. TaqMan method was used for genotyping nuclear factor, erythroid 2-related factor, NRF2 (rs6726395). A logistic Bayesian distributed lag interaction model (BDLIM) was used to evaluate the associations between prenatal PM10 exposure and childhood asthma by gender and NRF2. RESULTS: Exposure to PM10 during pregnancy was associated with the development of asthma (aOR 1.03, 95% CI 1.001.06). Stratifying by gender and NRF2 genotype, exposure to PM10 during 26-28 weeks gestation increased the risk of childhood asthma, especially in boys with NRF2 GG genotype. CONCLUSIONS: A critical window for PM10 exposure on the development of childhood asthma was during 26-28 weeks of gestation, and this was modified by gender and NRF2 genotype.

The association between MTHFR polymorphism, dietary methyl donors, and childhood asthma and atopy.

BACKGROUND: Studies investigating the genetic association of the C677T methylenetetrahydrofolate reductase (MTHFR) genotype and dietary methyl donors with asthma and atopy are limited, and have variable results. OBJECTIVE: To investigate the effect of dietary methyl donor intake on the risk of childhood asthma and atopy, based on the C677T polymorphism in the MTHFR gene. METHODS: This cross-sectional study included 2,333 elementary school children aged 6-8 years across Korea during 2005 and 2006, as part of the first Children's Health and Environmental Research survey. Genotyping for the MTHFR (rs1801133) polymorphism was performed using the TaqMan assay. Multivariable-adjusted logistic regression analysis was performed to determine a descriptive association between the dietary methyl donor intake, MTHFR polymorphism, and childhood asthma and atopy. RESULTS: Intake of dietary methyl donors like folates was significantly associated with a decreased risk of the wheezing symptom, in the past 12 months, and "ever asthma" diagnosis, respectively. Vitamin B6 intake was also associated with a decreased atopy risk. The T allele of the MTHFR (rs1801133) gene was significantly associated with a decreased risk of atopy. Increased intakes of folate, vitamin B2, and vitamin B6 were protective factors against atopy, especially in children with the T allele on the MTHFR gene, compared to those with lower intakes and the CC genotype. CONCLUSIONS: High intakes of dietary methyl donors were associated with reduced risk of atopy and asthma symptoms. These may have additive effects related to the susceptibility alleles of the MTHFR gene. The clinical implications require evaluation.

Combined effect of hygienic and polygenic risk scores in children with allergic rhinitis.

BACKGROUND: Although the development of allergic rhinitis (AR) is associated with multiple genetic and hygienic environmental factors, previous studies have focused mostly on the effect of a single factor on the development of AR. OBJECTIVE: This study aimed to investigate the combined effect of multiple genetic and hygienic environmental risk factors on AR development in school children. METHODS: We conducted a cross-sectional study, comprising 1,797 children aged 9-12 years. Weighted environmental risk score (ERS) was calculated by using four hygienic environmental factors, including antibiotic use during infancy, cesarean section delivery, breast milk feeding, and having older siblings. Weighted polygenic risk score (PRS) was calculated by using four single nucleotide polymorphisms (SNPs), including interleukin-13 (rs20541), cluster of differentiation 14 (rs2569190), toll-like receptor 4 (rs1927911), and glutathione S-transferase P1 (rs1695). Multivariable logistic regression analysis was used. RESULTS: More than three courses of antibiotic use during infancy increased the risk of current AR (adjusted odd ratio [aOR], 2.058; 95% confidence interval [CI]: 1.290-3.284). Having older siblings, especially > 2 (aOR, 0.526; 95%Cl: 0.303-0.913) had a protective effect. High ERS ( > median; aOR, 2.079; 95%Cl: 1.466-2.947) and PRS ( > median; aOR, 1.627; 95%Cl: 1.117-2.370) increased the risk of current AR independently. Furthermore, children who had both high ERS and PRS showed a higher risk of current AR (aOR, 3.176; 95%Cl: 1.787-5.645). CONCLUSIONS: Exposure to multiple hygienic risk factors during infancy increases the risk of AR in genetically susceptible children.

Food allergy in early childhood increases the risk of oral allergy syndrome in schoolchildren: A birth cohort study.

BACKGROUND: The level of pollen in Korea has increased over recent decades. Research suggests that oral allergy syndrome (OAS) may be more frequent in childhood than previously recognized. We aimed to investigate the prevalence and characteristics of OAS in children aged 6-10 years from a general-population-based birth cohort. METHODS: We analyzed 930 children from the cohort for childhood origin of asthma and allergic diseases (COCOA). Allergic diseases were diagnosed annually by pediatric allergists. The skin prick tests were performed with 14 common inhalant allergens and four food allergens for the general population of children aged 3 and 7 years. RESULTS: Of the 930 eligible children, 44 (4.7%) aged 6-10 years were diagnosed with OAS. The mean age at onset was 6.74 years. OAS prevalence was 7.2% among children with allergic rhinitis (AR) and 19.1% among those with pollinosis, depending on comorbidity. OAS was more prevalent in schoolchildren with atopic dermatitis, food allergy, and sensitization to food allergens and grass pollen in early childhood. In schoolchildren with AR, only a history of food allergy until the age of 3 years increased the risk of OAS (aOR 2.971, 95% CI: 1.159-7.615). CONCLUSION: Food allergy and food sensitization in early childhood were associated with OAS in schoolchildren with AR. Further study is required to elucidate the mechanism by which food allergy in early childhood affects the development of OAS.

Host-microbial interactions between PTGR2 and Bifidobacterium in the early life gut of atopic dermatitis children.

BACKGROUND: Gut microbiota dysbiosis is linked to the development and responses of the immune system and can play an important role in the onset of allergic diseases including atopic dermatitis (AD). This study investigated the association between host genetics and the gut microbiota in AD. METHODS: A global gene expression profiling of the gut epithelial colonocytes, genetic variations analysis, and the gut microbial composition analysis were performed. RESULTS: This study identified the upregulation of PTGR2 (p = .028), a gene involved in prostaglandin catalysis and inflammatory responses, as a potential risk factor for AD. In subsequent fine mapping analysis using 17 single nucleotide polymorphisms (SNPs) of PTGR2 in 864 Korean subjects (420 AD patients and 444 unaffected controls), several SNPs and haplotypes showed significant associations with AD and its SCORing AD (SCORAD) values (p = .002). To investigate host-microbial interactions, further gut microbiota data and genotypes were obtained from an independent cohort of 176 subjects (91 AD patients and 85 controls). From correlation analysis, a significantly negative association between SNP and Bifidobacterium abundance was observed in AD patients (p = .005). In additional observations of PTGR2-associated downstream molecules, NRF2 (p = .004) and several antioxidant genes (GSTT1, GCLC, GPX1; p < .05) showed significantly reduced expression in AD patients. CONCLUSIONS: Our current findings suggest that the interaction between PTGR2 dysregulated expression and a Bifidobacterium abundance affects a higher risk of AD and a more severe onset.

Longitudinal asthma exacerbation phenotypes in the Korean childhood asthma study cohort.

BACKGROUND: Asthma exacerbation (AE) leads to social and economic costs and long-term adverse outcomes. We aimed to predict exacerbation-prone asthma (EPA) in children. METHODS: The Korean childhood Asthma Study (KAS) is a prospective nationwide pediatric asthma cohort of children aged 5-15 years followed every 6 months. Patients with AE during the 6 months prior to all three visits, with AE prior to one or two visits, and without AE prior to any visit were defined as having EPA, exacerbation-intermittent asthma (EIA), and exacerbation-resistant asthma (ERA), respectively. Risk factors and prediction models of EPA were explored. RESULTS: Of the 497 patients who completed three visits, 42%, 18%, and 15% had exacerbations prior to visits 1, 2, and 3 and 5%, 47%, and 48% had EPA, EIA, and ERA, respectively. Univariate and multivariable logistic regression revealed forced expiratory volume in 1 s (FEV1) z-score, forced vital capacity (FVC) z-score, white blood cell (WBC) count, and asthma control test (ACT) score as relevant EPA risk factors. The EPA prediction model comprised FVC z-score, WBC count, ACT score, sex, and parental education level (area under the receiver operating characteristic curve [AUROC] 0.841 [95% confidence interval (CI): 0.728-0.954]). CONCLUSION: With appropriate management, AE decreases over time, but persistent AEs may occur. Apart from asthma control level, baseline lung function and WBC count predicted EPA.

Analysis of national surveillance of respiratory pathogens for community-acquired pneumonia in children and adolescents.

BACKGROUND: Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP. METHODS: The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020. RESULTS: A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports. CONCLUSIONS: This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.

Sublingual immunotherapy may be effective in reducing house dust mite allergies in children with atopic dermatitis.

AIM: We evaluated the efficacy of sublingual immunotherapy for children aged 5-17 years with atopic dermatitis who were allergic to house dust mites. METHODS: This open-label, controlled, randomised trial from June 2015 to February 2018 comprised 60 subjects from a specialist allergy centre in South Korea. Half received sublingual immunotherapy for 12 months and the other half formed the control group. The subjects were evaluated using specialist scores and specific immunoglobulin and skin prick tests. RESULTS: Sublingual immunotherapy significantly decreased the mean Scoring Atopic Dermatitis measurements in the sublingual group from baseline (30.2 ± 10.7) to 3 months (20.7 ± 8.5) and the effects persisted at 12 months (21.5 ± 12.4). However, the control group only showed a significant difference between baseline (30.4 ± 11.9) and 12 months (24.3 ± 10.2). The levels of Dermatophagoides farina-specific immunoglobulin G4 significantly increased in the treatment group from baseline (0.6 ± 0.5) to 12 months (1.0 ± 0.7), with no significant changes in the control group. New sensitisations to two or more allergens between baseline and 12 months were significantly lower in the sublingual group (21.4%) than controls (54.2%). CONCLUSION: Sublingual immunotherapy improved disease severity and prevented new sensitisations in children with atopic dermatitis who were allergic to dust mites.

A Case Report of Postinfectious Bronchiolitis Obliterans After Coronavirus Disease 2019 in a 10-Year-Old Child.

Coronavirus disease 2019 (COVID-19) is usually less severe in children and adolescents than in adults. However, it can cause severe respiratory illness in a small proportion of children with risk factors. Here, we report a rare case of a 10-year-old boy with postinfectious bronchiolitis obliterans that developed after pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This patient was previously healthy apart from a high body mass index (BMI, 30.13; 99.6th percentile for the age bracket), history of preterm birth (35 weeks), and low birth weight (1,850 g). He had persistent exertional dyspnea after recovering from SARS-CoV-2-related pneumonia. Spirometry revealed obstructive lung disease with the following results: predicted forced vital capacity (FVC%pred), 71%; forced expiratory volume in 1 second (FEV1%pred), 63%; FEV1/FVC, 0.81; and forced expiratory flow25-75%pred, 55%. Chest computed tomography showed multifocal areas of parenchymal hyperlucency and mosaic attenuation in both lungs. This case suggests that careful observation of children with obesity and low birth weight is necessary after recovery from SARS-CoV-2-related pneumonia.

Dog Ownership in Early Life Increased the Risk of Nonatopic Asthma in Children.

BACKGROUND: It is still debatable whether dog ownership during early childhood is a risk factor for the development of allergic diseases. OBJECTIVE: We investigated the association of dog ownership in early life with sensitization and asthma in childhood. METHODS: Data from the Cohort for Childhood Origin of Asthma and Allergic diseases were used to investigate the association between dog ownership at any time from pregnancy to 1 year of age and sensitization to aeroallergens at 3 and 7 years old, bronchial hyperresponsiveness (BHR), and asthma at 7 years old. We analyzed the cytokine levels in cord blood (CB) and indoor environmental measurement concentrations in the mother's residence obtained at 36 weeks of pregnancy. RESULTS: Sensitization to dogs at age 3 and 7 did not differ between dog ownership and nonownership, but dog ownership during early life decreased the risk of sensitization to aeroallergens at age 7 (aOR = 0.44, 95% CI 0.21-0.90). Dog ownership significantly increased the risk of nonatopic BHR (aOR = 2.86; 95% CI 1.32-6.21). In addition, dog ownership was associated with asthma, especially nonatopic asthma at 7 years old (aOR = 2.73, 95% CI 1.02-7.32; aOR = 7.05, 95% CI 1.85-26.90, respectively). There were no significant differences in the concentrations of IL-13 or interferon-γ in CB or indoor environmental measurements according to dog ownership during pregnancy. CONCLUSION: Early-life dog exposure in this birth cohort has been shown to reduce atopy but increase the risk of nonatopic BHR and nonatopic asthma at 7 years old.

Effect of early-life antibiotic exposure and IL-13 polymorphism on atopic dermatitis phenotype.

BACKGROUND: Although atopic dermatitis (AD) is associated with certain gene variants, the rapidly increasing incidence of AD suggests that environmental factors contribute to disease development. In this study, we investigated the association of AD incidence and phenotype with antibiotic exposure within 6 months of age, considering the dose administered and genetic risk. METHODS: This study included 1637 children from the COCOA cohort. Pediatric allergists assessed the presence of AD at each visit and obtained information about antibiotic exposure for more than 3 days. IL-13 (rs20541) polymorphism was genotyped by the TaqMan method. We stratified the AD phenotypes into four groups and used multinomial logistic regression models for analysis. RESULTS: Antibiotic exposure within 6 months of age was found to increase the risk of AD within 3 years of life (aOR = 1.40; 95% CI, 1.09-1.81) in dose-dependent manner. Antibiotic exposure more than twice increased the risk of the early-persistent AD phenotype (aOR = 2.50; 95% CI, 1.35-4.63). There was a weak interaction between genetic polymorphisms and environmental factors on the development of AD (p for interaction = 0.06). Children with the IL-13 (rs20541) GA + AA genotype have a higher risk of the early-persistent AD phenotype when exposed to antibiotics more than twice than those with the IL-13 (rs20541) GG genotype and without exposure to antibiotics (aOR = 4.73; 95% CI, 2.01-11.14). CONCLUSION: Antibiotic exposure within 6 months was related to the incidence of early-persistent AD and a dose-dependent increase in the incidence of AD in childhood, whose effect was modified by the IL-13 (rs20541) genotype.

Mid-pregnancy PM2.5 exposure affects sex-specific growth trajectories via ARRDC3 methylation.

Prenatal particulate matter <2.5 µm (PM2.5) is associated with adverse birth growth. However, the longitudinal growth impacts have been little studied, and no mechanistic relationships have been described. We investigated the association between prenatal PM2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM2.5 data measured by ordinary kriging from the COhort for Childhood Origin of Asthma and allergic diseases, followed up at 1, 3, and 5 years to evaluate growth. Differential DNA methylation and pyrosequencing of cord blood leukocytes was evaluated according to the prenatal PM2.5 levels and birth weight (BW). PM2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM2.5 levels [female, aOR 1.39 (95% CI 1.05-1.83); male, aOR 1.36 (95% CI 1.04-1.79)]. Bayesian distributed lag models with indoor PM2.5 adjustments revealed a sensitive window for BW effects at 10-26 weeks gestation, but only in females. Latent class mixture models indicated that a persistently low weight-for-height percentile trajectory was more prevalent in the highest PM2.5 exposure quartile at T2 in females, compared to a persistently high trajectory (36.5% vs. 20.3%, P = 0.022). Also, in the females only, the high PM2.5 and low BW neonates showed significantly greater ARRDC3 methylation changes. ARRDC3 methylation was also higher only in females with low weight at 5 years of age. Higher fetal PM2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism.

Innate Type 2 Response to Aspergillus fumigatus in a Murine Model of Atopic Dermatitis-like Skin Inflammation.

BACKGROUND: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). METHODS: We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1-/- mice five times per week, with repeat exposures at 2-week intervals. RESULTS: The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1-/- mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. CONCLUSIONS: Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

Association between sensitization and allergic diseases in 7-years-old Korean children.

BACKGROUND: Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children. OBJECTIVE: We characterized the association between sensitization patterns and allergic diseases. METHODS: A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. RESULTS: The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. CONCLUSIONS: The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Vegetable dietary pattern may protect mild and persistent allergic rhinitis phenotype depending on genetic risk in school children.

BACKGROUND: The effect of diet on allergic rhinitis (AR), its severity in children, and whether it modifies AR depending on genetic susceptibility are unknown. We investigated the association between dietary patterns and AR in school children and the influence of diet on AR according to a genetic risk score (GRS). METHODS: Totally, 435 7-year-old school children were recruited from the Panel Study on Korean Children. We used dietary patterns (vegetable, sugar, and meat) and dietary inflammatory index (DII) as dietary parameters. AR and its severity were defined by questionnaires about treatment in the previous 12 months and the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, respectively. A GRS was calculated using 6 single nucleotide polymorphisms for allergic diseases. RESULTS: A vegetable diet containing a lot of anti-inflammatory nutrients and higher vitamin D level in blood were negatively correlated, while DII was positively correlated with triglyceride level and triglyceride/HDL cholesterol. Vegetable diet (aOR, 95% CI = 0.73, 0.58-0.94) and DII (1.13, 1.01-1.28) were associated with AR risk. In particular, a high-vegetable diet resulted in a lower risk of mild and persistent AR (aOR, 95% CI = 0.24, 0.10-0.56) while a high DII represented a higher risk (2.33, 1.06-5.10). The protective effect of vegetable diet on AR appeared only among children with a lower GRS (adjusted P = .018). CONCLUSIONS: A vegetable dietary pattern characterized by high intake of anti-inflammatory nutrients and higher vitamin D level in blood might be associated with a lower risk of mild and persistent AR. This beneficial effect is modified by a genetic factor.

Prenatal PM2.5 exposure and vitamin D-associated early persistent atopic dermatitis via placental methylation.

BACKGROUND: The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 µm to 2.5 µm (PM2.5) and vitamin D on atopic dermatitis (AD) phenotypes have not been evaluated. DNA methylation and cord blood (CB) vitamin D could represent a plausible link between prenatal PM2.5 exposure and AD in an offspring. OBJECTIVE: To determine the critical windows of prenatal PM2.5 exposure on the AD phenotypes, if vitamin D modulated these effects, and if placental DNA methylation mediated these effects on AD in offspring. METHODS: Mother-child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PM2.5 was estimated by land-use regression models, and CB vitamin D was measured by chemiluminescence immunoassay. AD was identified by the parental report of a physician's diagnosis. We defined the following 4 AD phenotypes according to onset age (by the age of 2 years) and persistence (by the age of 3 years): early-onset transient and persistent, late onset, and never. Logistic regression analysis and Bayesian distributed lag interaction model were used. DNA methylation microarray was analyzed using an Infinium Human Methylation EPIC BeadChip (Illumina, San Diego, California) in placenta. RESULTS: PM2.5 exposure during the first trimester of pregnancy, especially during 6 to 7 weeks of gestation, was associated with early-onset persistent AD. This effect increased in children with low CB vitamin D, especially in those with PM2.5 exposure during 3 to 7 weeks of gestation. AHRR (cg16371648), DPP10 (cg19211931), and HLADRB1 (cg10632894) were hypomethylated in children with AD with high PM2.5 and low CB vitamin D. CONCLUSION: Higher PM2.5 during the first trimester of pregnancy and low CB vitamin D affected early-onset persistent AD, and the most sensitive window was 6 to 7 weeks of gestation. Placental DNA methylation mediated this effect.

Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.