Search

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.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.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.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.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.

Rationale: Exposure to humidifier disinfectants (HDs) can increase the risk of asthma, but the characteristics of HD-related asthma are currently unclear. Polyhexamethylene guanidine (PHMG)–contain...

BACKGROUND Bronchiolitis obliterans syndrome (BOS) is a life-threatening respiratory complication of allogeneic hematopoietic stem cell transplantation (HSCT). Although pulmonary function testing is crucial for monitoring BOS, little information exists on the association of these test results with outcomes in children with BOS. OBJECTIVES The purpose of this study was to determine the correlation between changes in lung function after BOS diagnosis and long-term outcomes. METHODS A total of 428 children underwent allogeneic HSCT from January 2006 to December 2017 at Asan Medical Center. Twenty-three (5.4%) were diagnosed with BOS after allogeneic HSCT, and their clinical data were reviewed. Twenty-one subjects underwent regular pulmonary function testing for 24 months after BOS diagnosis. RESULTS Among the 21 children with BOS, 8 died, 5 underwent lung transplantation (TPL), and 15 required oxygen (O2 ) therapy. The FEV1 % predicted (pred), FVC% pred, and FEF25%-75% pred were 37.8 ± 12.7% (mean ± SD), 62.2 ± 16.2%, and 16.4 ± 9.6%, respectively, at the time of BOS diagnosis. Changes in the FEV1 % pred were greater in the death and lung TPL groups (-24.8 ± 22.3%) than in the survival without lung TPL group (5.7 ± 21.8%) and greater in the O2 therapy (-19.4 ± 23.4%) group than in the group without O2 therapy (14.2 ± 20.0%) during the first 3 months after BOS diagnosis. CONCLUSION The change in FEV1 during the first 3 months after BOS diagnosis correlated with outcomes including survival, lung TPL, and O2 therapy. These results suggest that more active intervention in the first 3 months after BOS diagnosis may be needed to improve prognosis.

Background: Low-level laser (light) therapy is a promising technology that stimulates healing, relieves pain and inflammation, and restores function in injured body parts. However, few studies have compared the effects of lightemitting diodes of different fluence levels or different treatment durations. Objective: Here, we investigated the effects of various fluence levels and treatment durations on wound closure in mice. Methods: Full-thickness wounds were created on the dorsal skin using an 8-mm diameter punch, and the wounds were irradiated at 1, 4, or 40 J/cm2 for 5 consecutive days starting on day 1. To determine the optimal irradiation duration, wounds were irradiated at the most potent fluence of previous study for 5, 10, or 15 days. Photographic documentation, skin biopsies, and wound measurements were performed to compare the effects of different treatment parameters. Results: The most effective fluence level was 40 J/cm2 at day 5, as determined by monitoring wound closure. There were no statistically significant differences in wound healing with different durations. Conclusion: We have shown that repeated exposure to low levels of light significantly stimulates wound healing in mice and demonstrated more efficient wound closure with certain fluences of 830 nm irradiation. (Ann Dermatol 33(4) 318∼323, 2021)

We evaluated the efficacy of sublingual immunotherapy for children aged 5-17 years with atopic dermatitis who were allergic to house dust mites.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.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%).Sublingual immunotherapy improved disease severity and prevented new sensitisations in children with atopic dermatitis who were allergic to dust mites.

Atopic dermatitis (AD) and food allergy (FA) are associated with respiratory comorbidities, in the concept of 'atopic march.' However, children with AD and a coexisting FA have various disease courses, and the mechanism of atopic march remains unclear. In this study, we investigated whether the phenotype of AD with coexisting FA in early life affected asthma or allergic rhinitis (AR) in school children.A total of 1,579 children from the Panel Study on Korean Children (PSKC) cohort were followed-up in 2013. The participants diagnosed with AD in this cohort were classified by the age of AD onset and persistence as well as FA history. We compared the presence of comorbidities-asthma and rhinitis-among different AD phenotypes.Asthma and AR with current symptoms within 12 months at age 6-8 years were associated with early-onset persistent AD phenotype, regardless of coexisting FA. AD with FA conferred a higher risk of recent wheezing at 8 years of age than AD without FA (adjusted odds ratio, 8.09; 95% confidence interval, 2.54-25.76). Children with early-onset persistent AD with FA manifested a distinctive trajectory with a higher prevalence of wheezing and AR at age 5-8 years than those without AD.AD with FA in early life is strongly associated with asthma and AR in school children, and the early-onset persistent AD with FA had a strong additive effect on the risk of asthma at school age. Classifying AD phenotypes regarding FA in early life will help predict and prevent asthma and AR in school children.

Asthma exacerbation (AE) leads to social and economic costs and long-term adverse outcomes. We aimed to predict exacerbation-prone asthma (EPA) in children.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.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]).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.

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.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.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).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.

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.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.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.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.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.

An outbreak of fatal humidifier disinfectant lung injuries (HDLI) occurred in Korea. Human studies on mechanisms underlying HDLI have yet to be conducted. This study aimed to investigate methylation changes and their potential role in HDLI after exposure to HDs containing polyhexamethylene guanidine-phosphate. DNA methylation analysis was performed in blood samples from 10 children with HDLI and 10 healthy children using Infinium Human MethylationEPIC BeadChip. Transcriptome analysis was performed using lung tissues from 5 children with HDLI and 5 controls. Compared to healthy controls, 92 hypo-methylated and 79 hyper-methylated CpG sites were identified in children with HDLI at the statistical significance level of |Δβ|>0.2 and p

BackgroundUse of humidifier disinfectants (HD) at home leads to chemical airborne exposure, causing HD associated lung injury (HDLI) with high mortality. However, the lung function in children diagnosed with HDLI is not well studied. We investigated the effect of HD exposure on lung function, prognosis, and exposure characteristics associated with the lung function phenotype in children.MethodsEighty-one children diagnosed with HDLI in a nationwide cohort were tested for spirometry and diffusing capacity of the lung for carbon monoxide (DLco) from July 2013 and followed up with at five time points over 2 years. The results were compared with 122 children without HD exposure as controls. Home investigation and questionnaire analysis were conducted to assess HD inhalation exposure.ResultsHDLI survivor’s mean percent of predicted forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and corrected DLco were significantly lower compared with the control group. On longitudinal assessment, FVC was within the normal range, but flattened, and spirometry showed a predominantly restrictive pattern. Corrected DLco did not normalize above 80% despite increasing age. The persistently low phenotype of lung function was associated with initial exposure age, especially less than 12 months of age. Higher density HD exposure during sleep and close distance between the bed and the humidifier were significantly associated with persistently low corrected DLco.ConclusionsHD exposure affects prolonged decrement in lung function, especially DLco, particularly among children who are exposed within the first year of life. These results suggested that early-life HD exposure determines long-term prognosis of lung function in children.

The main advantages of the three-dimensional (3D) printing process are flexible design, rapid prototyping, multi-component structures, and minimal waste. For stereolithography (SLA) 3D printing, common photocurable polymers, such as bisphenol-A glycidyl methacrylate (Bis-EMA), trimethylolpropane triacrylate (TMPTMA), as well as urethane oligomers, have been widely used. For a successful 3D printing process, these photocurable polymers must satisfy several requirements, including transparency, a low viscosity, good mechanical strength, and low shrinkage post-ultraviolet curing process. Herein, we investigated SLA-type photocurable resins prepared using Bis-EMA, TMPTMA, and urethane oligomers. The flexural strength, hardness, conversion rate, output resolution, water absorption, and solubility of the printed materials were investigated. The degree of conversion of the printed specimens measured by infrared spectroscopy ranged from 30 to 60%. We also observed that 64–80 MPa of the flexural strength, 40–60 HV of the surface hardness, 15.6–29.1 MPa of the compression strength, and 3.3–14.5 MPa of the tensile strength. The output resolution was tested using three different structures comprising a series of columns (5–50 mm), circles (0.6–6 mm), and lines (0.2–5 mm). In addition, we used five different pigments to create colored resins and successfully printed complex models of the Eiffel Tower. The research on resins, according to the characteristics of these materials, will help in the design of new materials. These results suggests that acrylate-based resins have the potential for 3D printing.

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 1,637 children from the COCOA birth 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 4 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, 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.

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.

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.

The effects of prenatal particulate matter with an aerodynamic diameter ranging from 0.1 μm to 2.5 μm (PMTo determine the critical windows of prenatal PMMother-child pairs were enrolled from the birth cohort of the Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study. PMPMHigher PM

Purpose Interleukin (IL)-17 variants and perturbations in the gut microbiota may influence the development of atopic dermatitis (AD). However, unifying principles for variants of host and microbe interaction remains unclear. We sought to investigate whether IL-17 variants and gut microbiota affect the development of AD in infancy. Methods Composition of the gut microbiota was analyzed in fecal samples from 99 normal healthy and 61 AD infants at 6 months of age. The associations between total immunoglobulin E (IgE), the scoring atopic dermatitis (SCORAD), short-chain fatty acids, transcriptome and functional profile of the gut measured in these subjects and Streptococcus were analyzed. IL-6 and IL-8 in the human intestinal epithelial cell line (HIEC-6) were measured after stimulation of IL-17 and Streptococcus mitis. Results In this study, Streptococcus was enriched in infants with AD and was higher in those with the GA + AA of IL-17 (rs2275913) variant. Streptococcus was positively correlated with IgE and SCORAD in infants with AD and GA + AA of IL-17. Butyrate and valerate were negatively correlated with Streptococcus and were decreased in infants with AD and GA + AA. Bacterial genes for oxidative phosphorylation induced by reduced colonization of Clostridium were decreased compared with normal and GG. In transcriptome analysis, lactate dehydrogenase A-like 6B was higher in infants with AD compared with healthy infants. IL-6 and IL-8 were increased in IL-17 and/or S. mitis-stimulated HIEC-6 cells. Conclusions These findings suggest that increased Streptococcus and A allele of IL-17 (rs2275913) may contribute to the pathogenesis of AD via modulation of the immune system in infancy.

Photodynamic Therapy (PDT) is one of the standard treatment modalities for actinic keratoses (AKs). Daylight PDT (DL-PDT) with MAL cream, using daylight as light source, is one of recent treatment for AKs with less pain. Herein, we report cases of AKs successfully treated with DL-PDT in Asian patients. Four patients presented erythematous scaly patches and were diagnosed with AK by skin biopsy. The lesions were pretreated by fractional carbon dioxide laser first and then MAL creams were applied immediately. They went outdoors and exposed daylight for 2 h. They reported little pain of visual analogue scale 0. Clinically cleared lesions were observed with 1 month and 2 month follow-up. No complication such as oozing or scar was reported.

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.

Atopic dermatitis is a chronic, relapsing, inflammatory skin disease that usually appears in early childhood and develops into a heterogeneous disease during childhood. The clinical course and treatment for atopic dermatitis can differ according to its phenotype and/or endotype. This study aimed to identify clinical phenotypes of atopic dermatitis in early childhood. Data were obtained from 572 children under 3 years of age with atopic dermatitis. Cluster analysis applied to 11 variables, and we identified four clusters of atopic dermatitis. Children in cluster A (n = 141) had early-onset atopic dermatitis with high blood eosinophil counts, serum total immunoglobulin E and rates of sensitization to food allergens. Children in cluster B (n = 218) had early-onset atopic dermatitis with low blood eosinophil counts, serum total immunoglobulin E and rates of sensitization to both food and inhalant allergens. Children in cluster C (n = 53) had early-onset atopic dermatitis with high C-reactive protein levels and white blood cell counts. Children in cluster D (n = 160) had middle-onset atopic dermatitis with high serum total immunoglobulin E and rates of sensitization to inhalant allergens. Cluster A had the highest Scoring for Atopic Dermatitis and transepidermal water loss values. Age at onset, age at diagnosis, white blood cell count, eosinophil count, C-reactive protein and serum total immunoglobulin E level were the strongest predictors of cluster assignment. Analysis of these six variables alone resulted in correct classification of 95.5% of the subjects. These results support the heterogeneity of atopic dermatitis, even in early childhood.

Background The most relevant time of PM10 exposure to affect airway hyperresponsiveness (AHR) and new development of asthma in school-aged children is unclear. The aims of this study were to investigate the most critical time of PM10 exposure to affect AHR and new diagnosis of asthma from AHR in school-aged children. Methods Elementary schoolchildren (n = 3570) have been enrolled in a nationwide prospective 4-year follow-up survey in Korea from 2005 to 2006. Individual annual PM10 exposure was estimated by using an ordinary kriging method from the prenatal period to 7 years of age. AHR at 7 years was defined by a methacholine PC20 ≤8 mg/mL. Results PM10 exposure during pregnancy and at 1 year of age showed significant effects on AHR (aOR: 1.694, 95% CI: 1.298-2.209; and aOR: 1.750, 95% CI: 1.343-2.282, respectively). PM10 exposure during pregnancy was associated with the risk of a new diagnosis of asthma (aOR: 2.056, 95% CI: 1.240-3.409), with the highest risk in children with AHR at age 7 (aOR: 6.080, 95% CI: 2.150-17.195). PM10 exposure in the second trimester was associated with the highest risk of a new diagnosis of asthma in children with AHR at age 7 (aOR: 4.136, 95% CI: 1.657-10.326). Conclusions Prenatal PM10 exposure in the second trimester is associated with an increased risk of a new diagnosis of asthma in school-aged children with AHR at 7 years. This study suggests that PM10 exposure during a specific trimester in utero may affect the onset of childhood asthma via AHR.

Primary cicatricial alopecia (PCA) is a dermatological challenge. Because no large-scale epidemiological study regarding PCA is available yet, we investigated the National Health Insurance Service-National Sample Cohort for patients diagnosed with PCA. The annual and overall rates of incidence and prevalence of PCA during the study period (2004-2013) were estimated. Distribution of PCA subtypes, disease co-occurrence rates and frequently prescribed medications were also evaluated. The overall incidence was 6.10 (95% confidence interval [CI], 5.62-6.60) per 100 000 person-years. The incidence rate was stable over time (risk ratio [RR] = 1.012, P = 0.201) and lower in female patients (RR = 0.718, P < 0.001). The overall prevalence was 20.93 (95% CI, 17.97-23.86) per 100 000 persons. The average duration of PCA was calculated as 3.23 years. Approximately 70% of the patients were below the age of 45 years. Folliculitis decalvans and dissecting cellulitis were the most common subtypes of PCA. Logistic regression analysis showed that PCA was significantly associated with thyroid disorders (adjusted odds ratio = 1.64, P < 0.001). Clobetasol was the most frequently prescribed topical agent. Corticosteroids were the most common oral agents used, followed by tetracycline antibiotics. Our study is the first large-scale study reporting the epidemiology of PCA. We found a preponderance of males and neutrophil-associated subtypes of PCA, and PCA was related to thyroid disorders.

BACKGROUND A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

Prenatal particulate matter

SummaryBackground Microbial colonization of the airway plays a role in the pathogenesis of asthma; however, the effect of the upper airway microbiome on childhood asthma is not fully understood. We analyzed the metagenome of airway microbiome to understand the associated role of upper airway microbiome with the natural course of childhood asthma. Methods Nasopharyngeal swabs were collected from children with asthma, those in asthma remission, and control groups. High-throughput sequencing was used to examine the structure and functional dynamics of the airway microbiome with respect to asthma phenotypes. Results The composition of microbiota differed among healthy control, asthma, and remission groups. The relative abundance of Streptococcus was negatively associated with FEV1% predicted (p = 0.023), and that of Staphylococcus was negatively associated with methacholine PC20 (p = 0.013). Genes related to arachidonic acid metabolites, lysine residues, and glycosaminoglycans in the microbiome could be associated with airway inflammation. In particular, genes related to synthesis of anti-inflammatory prostaglandin E2 were not detected from the airway microbiome in the asthma group. Conclusions These data suggest that alterations in the composition and function of the upper airway microbiome could be related with the natural course of asthma in children. This article is protected by copyright. All rights reserved.

In South Korea, a cluster of humidifier disinfectant-induced lung injury (HDLI) cases developed between 2006 and 2011. There are no existing reports regarding the rate of humidifier disinfectant (HD) usage in the general population of Korean children. The purpose of this study was to investigate the rate of humidifier and HD usage in the general population of Korean children. This is a general population-based birth cohort multicenter study, Panel Study of Korean Children (PSKC) from 2008, a humidifier and HD-related questionnaire administered to 1577 subjects (809 male, 768 female) in 2015 (n=1577). The questionnaire consisted of four categories (humidifier usage, HD usage, exposure duration, and type of HD brands). A total of 75.6% (1192/1577) had used a humidifier, and the rate of HD usage was found to be 31.1% (409/1316). Polyhexamethylene guanidine (PHMG), used as a disinfectant, was found to have the highest usage rate (62.0%). HD was used for less than 3 months of the entire lifetime of most of the subjects. In conclusion, approximately 30% of young Korean children were exposed to HD. PHMG-containing HD was the most commonly used. These results suggest that a nationwide epidemiologic investigation is needed urgently, and children exposed to HD should be investigated regarding their status of lung injury, including a pulmonary function test. Moreover, a long-term follow-up period may be required to evaluate HD usage-associated lung injury.

Objective: Mold exposure in early life may be associated with development of atopic dermatitis; however, studies of this link are inconclusive and evidence for the underlying mechanism(s) is lacking. This study identified the association between the time of mold exposure and development of atopic dermatitis and investigated the underlying mechanisms. Method: The association between atopic dermatitis and mold exposure was examined in the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study (n = 1446). Atopic dermatitis was diagnosed at 1 year of age by pediatric allergists. Exposure to mold was assessed by questionnaire. The Illumina MiSeq platform was used to examine the environmental mycobiome in 20 randomly selected healthy infants and 20 infants with atopic dermatitis at 36 weeks of gestation. Results: Prenatal, but not postnatal, mold exposure was significantly associated with atopic dermatitis (adjusted odds ratio, 1.36; 95% confidence interval, 1.01-1.83). Levels of total serum IgE at 1 year of age were higher in infants with atopic dermatitis exposed to mold during pregnancy than in healthy infants not exposed to mold during pregnancy (p = 0.021). The relative abundance of uncultured Ascomycota was higher in infants with atopic dermatitis than in healthy infants. The relative abundance of uncultured Ascomycota correlated with total serum IgE levels at 1 year of age (r = 0.613, p

Purpose Asthma is a heterogeneous airway disease occurring in children, and it has various clinical phenotypes. A clear differentiation of the clinical phenotypes can provide better asthma management and prediction of asthma prognosis. Little is currently known about asthma phenotypes in Korean children. This study was designed to identify asthma phenotypes in school-aged Korean children. Methods This study enrolled 674 children with physician-diagnosed asthma from the Korean childhood Asthma Study (KAS) cohort. The physicians verified the relevant histories of asthma and comorbid diseases, as well as airway lability and hyper-responsiveness from the results of pulmonary function tests and bronchial provocation tests. Questionnaires regarding the participants' baseline characteristics, their environment and self-rating of asthma control were collected at the time of enrollment. Laboratory tests were performed to assess allergy and airway inflammation. Children with asthma were classified by hierarchical cluster analysis. Results Of the 674 patients enrolled from the KAS cohort, 447 were included in the cluster analysis. Cluster analysis of these 447 children revealed 4 asthma phenotypes: cluster 1 (n = 216, 48.3%) which was characterized by male-dominant atopic asthma; cluster 2 (n = 79, 17.7%) which was characterized by early-onset atopic asthma with atopic dermatitis; cluster 3 (n = 47, 10.5%) which was characterized by puberty-onset, female-dominant atopic asthma with the low lung function; and cluster 4 (n = 105, 23.5%) which was characterized by early-onset, non-atopic dominant asthma. Conclusions The asthma phenotypes among Korean children can be classified into 4 distinct clusters. Long-term follow-up with these phenotypes will be needed to define their prognosis and response to treatment.

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. Conclusion 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.

Purpose Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. Methods This study was performed on 667 children aged 5-15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. Results Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. Conclusions Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.

Objective: Various numerical asthma control tools have been developed to distinguish different levels of symptom control. We aimed to examine whether the asthma control test (ACT) is reflective of objective findings such as lung function, fractional exhaled nitric oxide (FeNO) and laboratory data in patients with stable asthma. Methods: We included patients who were enrolled in the Korean Childhood Asthma Study. ACT, spirometry, blood tests and FeNO were performed in patients after stabilization of their asthma. We examined differences among spirometry parameters, blood tests and FeNO according to control status as determined by ACT and investigated for any significant correlations. Results: The study population consisted of 441 subjects. Spirometry showed that forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity and FEV1/forced vital capacity were all significantly higher in the controlled asthma group. Likewise, FeNO and percent-change in FEV1 were both significantly lower in the controlled asthma group. In blood tests, the eosinophil fraction was significantly lower in the controlled asthma group while white blood cell count was significantly higher in the controlled asthma group. Lastly, among the various factors analyzed, only provocative concentration of methacholine causing a 20% fall in FEV1 significantly correlated with ACT score. Conclusion: ACT is useful as part of the routine evaluation of asthmatic children and should be used as a complement to existing tools such as spirometry and FeNO measurement.

Objectives To investigate the association between particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5 ) exposure during each trimester of pregnancy and development of lower respiratory tract infections (LRTIs) during the first 3 years of life and whether GSTM1 gene polymorphisms modify these effects. Methods This study included 1,180 mother-child pairs from the Cohort for Childhood Origin of Asthma and allergic diseases. The PM2.5 levels during pregnancy were estimated by residential address using land-use regression models based on a national monitoring system. A diagnosis of LRTIs was based on a parental report of a physician's diagnosis. Real-time polymerase chain reaction was used for GSTM1 genotyping. Results Higher PM2.5 exposure during the third trimester was associated with LRTIs at 1 year of age (aRR, 1.06; 95% CI, 1.00-1.13). This result did not change after adjusting for PM2.5 exposures during the first and second trimesters (aRR, 1.06; 95% CI, 0.99-1.13). This association was significant after adjusting for PM2.5 exposures during first year of age (aRR, 1.08; 95% CI, 1.02-1.15) and exposures to NO2 and ozone at the third trimester (aRR, 1.07; 95% CI, 1.00-1.16). In addition, PM2.5 exposure during the third trimester increased the risk of LRTIs at 1 year of age in cases with the GSTM1 null genotype (aRR, 1.26; 95% CI, 1.01-1.57; P for interaction .20). Conclusion Higher PM2.5 exposure during the third trimester of pregnancy may increase the susceptibility to LRTIs at 1 year of age. This effect is modified by GSTM1 gene polymorphisms.

Background Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. Methods We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects’ baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. Discussion Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects’ personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

Aim We investigated airway function in preschoolers with postinfectious bronchiolitis obliterans (PIBO) using impulse oscillometry (IOS). Methods This study enrolled 182 children aged three to five years: 12 with PIBO, 135 with asthma and 35 nonatopic controls. Respiratory resistance and reactance were assessed using IOS. Results The percentage predicted (% predicted) of prebronchodilator respiratory resistance at 5 Hz was significantly higher in children with PIBO (177.9 ± 118.4%) than the asthma (126.1 ± 30.5%, p = 0.013) or control (121.1 ± 21.8%, p = 0.014) groups. After bronchodilator use, children with PIBO did not reach the values of Rrs5% predicted in the asthma and control groups. Respiratory reactance (Xrs5% predicted) in children with PIBO (337.1 ± 478.5%) was significantly higher than both asthma (130.0 ± 80.0%, p = 0.004) and control (105.1 ± 30.8%, p

Purpose To investigate potential differences in the frequency of preterm births (PTB) between pregnancies with or without prophylactic cerclage in women with a history of conization. Materials and methods We identified women who had their first singleton delivery after conization between 2013 and 2018 using records in the National Health Insurance Service of Korea claims database. We only included women who had undergone a health examination and interview within 2 years before delivery. We used timing of maternal serum alpha-fetoprotein (MSAFP) tests to differentiate early (before) from late (after the MSAFP test) cerclage. The frequency of adverse pregnancy outcomes, including PTB, preterm labor and premature rupture of membranes, antibiotics and tocolytics use, cesarean delivery, and number of admissions before delivery, were compared. Results A total of 8322 women was included. Compared to the no cerclage group (n=7147), the risks of adverse pregnancy outcomes were higher in the cerclage group (n=1175). After categorizing patients with cerclage into two groups, the risk of PTB was still higher in the early cerclage group than in the no cerclage group after adjusting for baseline factors (4.48%, 30/669 vs. 2.77%, 159/5749, odds ratio 2.42, 95% confidence interval 1.49, 3.92). Other adverse pregnancy outcomes were also more frequent in the early cerclage group than the no cerclage group. Conclusion Early cerclage performed before MSAFP testing does not prevent PTB in pregnancy with a history of conization, but increases the risk of adverse pregnancy outcomes, including PTB.

Purpose Interleukin (IL)-17 variants and perturbations in the gut microbiota may influence the development of atopic dermatitis (AD). However, unifying principles for variants of host and microbe interaction remains unclear. We sought to investigate whether IL-17 variants and gut microbiota affect the development of AD in infancy. Methods Composition of the gut microbiota was analyzed in fecal samples from 99 normal healthy and 61 AD infants at 6 months of age. The associations between total immunoglobulin E (IgE), the scoring atopic dermatitis (SCORAD), short-chain fatty acids, transcriptome and functional profile of the gut measured in these subjects and Streptococcus were analyzed. IL-6 and IL-8 in the human intestinal epithelial cell line (HIEC-6) were measured after stimulation of IL-17 and Streptococcus mitis. Results In this study, Streptococcus was enriched in infants with AD and was higher in those with the GA + AA of IL-17 (rs2275913) variant. Streptococcus was positively correlated with IgE and SCORAD in infants with AD and GA + AA of IL-17. Butyrate and valerate were negatively correlated with Streptococcus and were decreased in infants with AD and GA + AA. Bacterial genes for oxidative phosphorylation induced by reduced colonization of Clostridium were decreased compared with normal and GG. In transcriptome analysis, lactate dehydrogenase A-like 6B was higher in infants with AD compared with healthy infants. IL-6 and IL-8 were increased in IL-17 and/or S. mitis-stimulated HIEC-6 cells. Conclusions These findings suggest that increased Streptococcus and A allele of IL-17 (rs2275913) may contribute to the pathogenesis of AD via modulation of the immune system in infancy.

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.

Background Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease. Great efforts have been recently made to treat AD using mesenchymal stem cells (MSCs), which have immunomodulatory functions. However, the immunomodulatory effects of MSCs need to be enhanced for clinical application in the treatment of AD. Objectives To evaluate and characterise the therapeutic effects of human Wharton’s jelly-derived MSCs (WJ-MSCs) primed with the Toll-like receptor 3 agonist poly I:C or interferon-γ (IFN-γ) in a murine model of AD. Methods Mice were treated with Aspergillus fumigatus extract to induce AD and then subcutaneously injected with non-primed, poly I:C-primed or IFN-γ-primed WJ-MSCs. Clinical symptom scores, transepidermal water loss (TEWL), histological characteristics and cytokine levels were determined. Transcriptome profiling and pathway analyses of primed WJ-MSCs were conducted. Results The clinical symptom score and TEWL in skin lesions were reduced in mice administered non-primed and primed WJ-MSCs. Epidermal thickness and inflammatory cell infiltration in skin lesions were reduced more in mice administered primed WJ-MSCs than in mice administered non-primed WJ-MSCs. Secretion of interleukin-17 was significantly reduced in skin draining lymph nodes of mice administered primed WJ-MSCs. Genomics and bioinformatics analyses demonstrated the enrichment of certain pathways specifically in WJ-MSCs primed with poly I:C or IFN-γ. Conclusions Priming with poly I:C- or IFN-γ improved the therapeutic effects of WJ-MSCs in a murine model of AD. This study suggests that priming with poly I:C or IFN-γ enhances the immunomodulatory functions of WJ-MSCs and can be used as a novel therapeutic approach for AD. Electronic supplementary material The online version of this article (10.1186/s13287-019-1164-6) contains supplementary material, which is available to authorized users.

Objectives Swallowing difficulties are best assessed by videofluoroscopic swallowing studies (VFSS). However, limiting radiation exposure is important, especially in young children. The purpose was to evaluate radiation dose in young children during VFSS, and to investigate factors associated with it. Methods Children with swallowing difficulty who underwent VFSS from February 2012 to July 2014 were recruited. Dose area product (DAP) and screening time were offered by the fluoroscopy machine, and effective dose was calculated from the DAP using a conversion coefficient published by the National Radiological Protection Board (NRPB-R262). The age, gender, height, weight, body mass index (BMI), body surface area (BSA), underlying disease of the subject children, and results of VFSS were investigated. Results In 89 children (mean age 1.57 ± 2.17, 55 boys and 34 girls), mean effective dose was 0.29 ± 0.20 mSv, mean DAP was 2.41 ± 1.65 Gy cm2, and mean screening time was 2.24 ± 0.99 min. The effective dose correlated with the screening time (r = 0.598, p Conclusions The effective dose during VFSS (0.29 mSv) in young children, which is affected by screening time, age, and body size, is considerably lower than the pediatric radiation exposure limit of 1 mSv per year. However more than 4 VFSS annually would exceed this limit. Our findings will help physicians to reduce the radiation exposure and provide a useful references for future pediatric VFSS guidelines.