Neurodevelopment in Term Infants with Normal Birthweight following Postnatal Systemic Steroid Exposure.

INTRODUCTION: Studies investigating the potential impact of systemic steroid exposure during early infancy on neurological development in full-term infants with normal birth weight are lacking. METHODS: This population-based administrative cohort study used data of national health insurance and a health-screening program for infants and children and included full-term infants who were born in Korea between 2008 and 2012 with normal birth weight and did not have any specific perinatal or neurodevelopmental diseases. The prescription of systemic steroids within the first 3 months of age was mainly considered. The neurological development of children was assessed using the Korean Development Screening Test (K-DST) at 6 years of age. To balance the baseline characteristics of the control and exposed groups, stabilized inverse probability of treatment weighting with trimming was performed in the main cohort. Ordinal logistic regression was used to assess the association between systemic steroid exposure and unfavorable results in the K-DST. RESULTS: The control and exposure groups had 246,168 and 5,083 children, respectively. The K-DST suggested unfavorable results in 8.1% and 8.6% children in the control and exposure groups, respectively (weighted odds ratio, 95% confidence interval, 1.03, 0.93-1.14). When each domain of the K-DST was considered separately, the risk of unfavorable results in the exposed group was not significantly different from that in the control group. CONCLUSIONS: No significant association was observed between exposure to systemic steroids during early infancy and neurodevelopmental impairment at 6 years of age.

Total airway mechanics and fractional exhaled nitric oxide levels of children living in banjihas (semi-basements).

BACKGROUND: The ISAAC phase III study in Korea found a higher incidence of wheezing illnesses among residents in basements or semi-basements. OBJECTIVE: This study investigates the link between living in banjihas (semi-basements) and airway resistance and Th2 airway inflammation in Korean children, compared to those on higher floors. METHODS: We assessed 575 fifth- and sixth-grade students (aged 10-12) in an inner-city area of South Korea. The study utilized impulse oscillometry to measure small and total airway resistance (Rrs20-5 and Rrs0, respectively) and Fractional Exhaled Nitric Oxide (FeNO) measurements to evaluate airway inflammation. We also considered a range of biological and environmental factors, including allergen sensitization, serum 25-hydroxyvitamin D levels, and urinary metabolites like VOCs, bisphenol, and triclosan. Participants were categorized by living floors: banjihas, first-fifth floors, and sixth floors or higher. RESULTS: Twenty-five children (4.3%) lived in banjihas, 311 (54.1%) on the first to fifth floor, and 239 (41.6%) on the sixth floor or above. Despite similar levels of allergen sensitization and urinary pollutant metabolite levels across all groups, banjiha dwellers showed significantly higher total airway resistance (adjusted &1: 0.633, 95%CI: 0.156, 1.109; P = 0.009) and a greater prevalence of elevated FeNO levels (> 35 ppb) (P = 0.033). These findings persisted after adjusting for critical factors like height, gender, BMI z-score, and birth conditions. CONCLUSION: Children in banjihas exhibit elevated airway resistance and FeNO levels independently of allergen sensitization or pollution exposure, underscoring the necessity for enhanced focus on their respiratory health in such living conditions.

Atmospheric environment and persistence of pediatric asthma: A population-based cohort study.

BACKGROUND: Asthma is a heterogeneous disease with different outcomes. For children with asthma at the age of 7 years, 67-75% are symptom-free as adults. Data on the important link between childhood and adult asthma are sparse. OBJECTIVE: We aimed to investigate factors associated with persistence of childhood asthma over three years of follow-up by linking data between Korea childhood Asthma Study (KAS) and their matched claims data from Health Insurance Review and Assessment Service (HIRA). METHODS: We analyzed data from 450 preadolescent children aged 7 to 10 years and classified them into remission or persistence groups. Baseline clinical characteristics and exposure to air pollution materials including PM2.5 and PM10 during three years of follow-up were compared. The main outcome was asthma persistence which was defined as the presence of asthma episodes with healthcare utilization and prescription of asthma medications within three years after KAS enrollment. RESULTS: At the third year of follow-up, after stepwise regression analysis, lower age at enrollment (adjusted odds ratio (aOR): 0.79; 95% confidence interval (CI): 0.64-0.96), male sex (aOR: 1.66; 95%CI: 1.05-2.63), proximity from an air-polluting facility (aOR: 2.4; 95%CI: 1.34-4.29), higher level outdoor PM2.5 (aOR: 1.1; 95%CI: 1.02-1.20), and higher rate of doctor-diagnosed food allergy (FA) (aOR: 2.33; 95%CI: 1.06-5.12) were significantly associated with persistence. CONCLUSION: We discovered various independent risk factors for the persistence of childhood asthma. By linking HIRA claims data, we could clarify risk factors for persistence in a well-defined study population.

Growth pattern during early infancy, body mass index during childhood and childhood asthma.

BACKGROUND: There is a lack of longitudinal studies of associations between growth from infancy to childhood and asthma development. OBJECTIVE: The objective of the study was to investigate the effects of weight change during infancy, body mass index (BMI) and the interaction of these factors on the risk of childhood asthma. METHODS: We enrolled children born in 2008 and 2009 at full-term and with normal birth weight. The weight change in infancy was grouped into slow, on-track and rapid. BMI status in childhood was stratified into low, normal and high groups and used as a time-varying variable. The outcome was asthma, defined as two or more diagnoses of asthma separated by at least 1 year after 2 years of age. The risk of asthma was assessed using Cox proportional hazard regression, with adjustment for sex, residence area at birth, economic status and feeding types in infancy. RESULTS: Of 917,707 children born in Korea in 2008 and 2009, 271,871 were eligible for analysis. The risk of asthma was greater in groups with low birth weight (aHR 1.06, 95% CI 1.04 to 1.08), rapid body weight change during early infancy (aHR 1.08, 95% CI 1.07 to 1.10) and high BMI during childhood (aHR 1.06, 95% CI 1.04-1.08). The interaction of weight change during early infancy with BMI during childhood was significant for asthma (p < .01). Rapid weight gain in infancy was associated with lower risk of asthma in those with low BMI during childhood; had no association with asthma in those with normal BMI during childhood; and was associated increased asthma risk in those with high BMI during childhood-aHR 1.26 (95% CI 1.19 to 1.33) and aHR 1.33 (95% CI 1.12 to 1.56) compared with on-track and slow infant weight gain, respectively. CONCLUSION: Low birth weight, high BMI during childhood and, in those with high childhood BMI, rapid weight gain during early infancy are associated with increased risk of childhood asthma.

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.

Association between complementary food introduction before age 4 months and body mass index at age 5-7 years: A retrospective population-based longitudinal cohort study.

BACKGROUND: The optimal time of starting complementary foods (CFs) in infants remains a subject of debate. This population-based longitudinal cohort study evaluated the association between early CF introduction and body mass index (BMI) in children aged 5-7 years. METHODS: The present study included 917,707 children born in Korea during 2008-2009. Initial timing of CF introduction was obtained by questionnaires administered between 4 and 6 months and 9 and 12 months of age. The cohort consisted of 154,565 eligible individuals who properly completed the screening programme, including structured questionnaires, anthropometric measurements and physical examinations. To balance baseline characteristics, children were subjected to propensity score matching based on 95 covariates, including indicators of baseline health such as perinatal condition, birth weight, economic status, clinical disease and drug exposure. Exposure was defined as introduction to CF at age < 4 months, and outcomes were overweight (BMI z-score > 85th percentile) and obesity (BMI z-score > 95th percentile) at ages 5-7 years. RESULTS: Of the 154,565 eligible children in the observed cohort, 10,499 (6.8%) were introduced to CF at age < 4 months and 144,066 (93.2%) at age ≥ 4 months. Propensity score matching yielded 9680 children introduced to CF at age < 4 months and 35,396 at age ≥ 4 months. The risk for being overweight or obese at age 5-7 years was slightly higher among those who started CF at age < 4 months than at age ≥4 months (adjusted relative risk = 1.06; 95% confidence interval = 1.02-1.09). A similar but stronger association was observed for being obese at age 5-7 years (adjusted relative risk = 1.12; 95% confidence interval = 1.05-1.19). CONCLUSIONS: Early CF introduction before age 4 months was associated with increased BMI at age 5-7 years.

Neurodevelopment at 6 years of age in children with atopic dermatitis.

BACKGROUND: Few studies have reported an association between atopic dermatitis and cognitive impairment in children. Therefore, we evaluated the association between atopic dermatitis (AD) and neurodevelopmental dysfunction in children. METHODS: We analyzed 2,395,966 children born between 2008 and 2012 in Korea. All data were acquired from the databases of the Korean National Health Insurance System. AD was defined as five or more diagnoses before age 24 months. The outcome was suspected neurodevelopmental dysfunction in the gross motor skill, fine motor skill, cognition, language, sociality, and self-care domains of the Korean Developmental Screening Test for Infants and Children at age 6 years. The positive control outcome was defined as attention deficit hyperactive disorder (ADHD). The associations were assessed using ordinal logistic regression, adjusting for asthma and allergic rhinitis. RESULTS: Among the eligible children, 89,452 and 30,557 were allocated to the control and AD groups, respectively. In the weighted data, the AD group showed a higher risk of suspected neurodevelopmental dysfunction in the total score (weighted adjusted odds ratio [95% CI] 1.10 [1.05-1.16]), gross motor skills (1.14 [1.04-1.25]), and fine motor skills (1.15 [1.06-1.25]) than the control group. The AD with steroids or hospitalization groups showed an increased risk of suspected neurodevelopmental dysfunction. In addition, the AD group showed a significant association with mental retardation, psychological development disorder, and behavioral and emotional disorders as well as ADHD. CONCLUSIONS: AD before age 2 years may be associated with an increased risk of neurodevelopmental dysfunction including gross and fine motor skills in the young childhood period.

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.

Growth and micronutrient levels of 6-12 years-old children with food allergies, food sensitisation, and food restrictions.

AIM: We investigated the association of food allergy, food sensitisation, and food restriction with growth and micronutrients levels in schoolchildren. METHODS: A total of 195 schoolchildren (6-12 years old) from six elementary schools in Korea were enrolled, and questionnaires were administered to their parents during June and July 2015. Food allergy was defined by the presence of urticaria, skin rash, pruritus, throat tightness, gastrointestinal complaints, or respiratory difficulty after consumption of a food to which allergy was plausible during the past 12 months. Skin prick tests were performed and serum levels of haemoglobin and micronutrients were measured. RESULTS: Among 195 participants (51.3% males) enrolled, 35 (17.9%) were reported to have food allergies, 17 (8.7%) were on food restriction, and 27 (14.0%) were sensitised to at least one food allergen. Food allergy and food restriction were associated with a lower height-for-age z-score (p for trend = 0.018, p = 0.048; p for trend = 0.076, p = 0.008). Food restriction was related to reduced serum calcium level (aOR: -0.094, 95% CI: -0.156 to -0.032). CONCLUSION: Signs and symptoms of food allergy and consequent food restrictions in children were related to lower height-for-age z-score and lower serum calcium levels.

Association of phthalate exposure and airway dysfunction with mediation by serum periostin.

BACKGROUND: Phthalates can cause respiratory and immunological disorders. However, little is known about the role of serum periostin and YKL-40 levels in mediating the effects of phthalates. We investigated the mediating role of these biomarkers in the relationship between phthalates and airway dysfunction. METHODS: A total of 487 children (aged 10-12 years old) were examined. Four high-molecular-weight phthalate (HMWP) [Σ4 HMWP] metabolites and 3 low-molecular-weight phthalate (LMWP) [Σ3 LMWP] metabolites in urine samples were measured. Serum periostin and YKL-40 levels were measured. Airway function was measured using impulse oscillometry. A mediation model was used to quantify the mediating effects of periostin and YKL-40 on airway dysfunction. RESULTS: After adjustment for height, gender, BMI z-score, aeroallergen sensitization, secondary smoking, and vitamin D level, the level of urinary Σ3 LMWP metabolites was significantly associated with respiratory system resistance at 5 Hz (Rrs5; adjusted ß: 0.020, 95% CI: 0.005-0.034; p = .010). The levels of urinary Σ4 HMWP and Σ3 LMWP metabolites were significantly associated with periostin level, but not with YKL-40 level. In addition, the periostin level was associated with Rrs5 (adjusted ß: 0.048, 95% CI: 0.015-0.081; p = .005) and Rrs20-5 (adjusted ß: 0.040, 95% CI: 0.011-0.069; p = .007). Serum periostin level had a significant effect in mediating the relationship between Σ3 LMWP and Rrs5 (13.9%, 95% CI: 10.7-77.0; p < .001). CONCLUSION: Exposure to LMWPs was significantly associated with airway dysfunction, and this effect was partially attributable to increased serum periostin level.

Association of serum lipid parameters with the SCORAD index and onset of atopic dermatitis in children.

BACKGROUND: The association between dyslipidemia and atopic dermatitis in children is unclear. This study investigated the association between dyslipidemia and atopic dermatitis in children by analysis of disease onset, risk factors, and disease severity. METHODS: Subset I examined 7-year-old children in elementary school (n = 248), and Subset II was a retrospective long-term follow-up hospital-based study (n = 52 725) conducted from 1986 to 2016 that used propensity score matching. In the Subset I study, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were determined, and the SCORing Atopic Dermatitis (SCORAD) index was determined. In the Subset II study, the time of atopic dermatitis onset was determined for asymptomatic subjects whose TC levels were below or above 170 mg/dL. RESULTS: Our Subset I study indicated that children with atopic dermatitis (n = 69, 27.8%) had significantly higher levels of TC and TG, and that the SCORAD index had significant associations with high levels of TC and TG, and a low level of HDL-C. Our Subset II study (1722 with high TC and 6735 with normal TC after propensity score matching) indicated the high TC group had a greater hazard ratio (HR) for the onset of atopic dermatitis (consensus-based HR: 2.47; 95% CI: 1.23, 5.06, P = .012) during 5 years. CONCLUSION: An abnormal blood lipid profile in children is associated with the presence of atopic dermatitis and the SCORAD index. The risk of atopic dermatitis onset was significantly greater with high levels of TC.

Asthma control test reflects not only lung function but also airway inflammation in children with stable 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.

Serum YKL-40 Levels Are Associated with the Atherogenic Index of Plasma in Children.

YKL-40, also known as chitinase-3-like protein 1, is an inflammatory glycoprotein that is secreted by various cell types under acute, chronic, and subclinical inflammation conditions. Elevated serum YKL-40 levels are reportedly independently related to diabetes mellitus, coronary artery disease, acute myocardial infarction, and cardiovascular mortality in adults. Therefore, we aimed to investigate the relationship between serum YKL-40 levels, lipid abnormalities, and the atherogenic index of plasma (AIP) in children. We enrolled 479 children aged 10-12 years (mean age: 11.52) in this general population-based, cross-sectional study. All subjects completed questionnaires and were subjected to multifrequency bioelectrical impedance analysis (BIA) to measure their height, weight, and body mass index (BMI). We collected serum samples from all participants to measure YKL-40, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. Mean serum YKL-40 levels were significantly higher in the low-HDL-C (p = 0.017) and high-TG (p = 0.010) groups but were not related to TC and LDL-C levels. YKL-40 levels were also higher in the high AIP group (p = 0.007). After adjusting for age, gender, and BMI z-score, the associations between serum YKL-40 levels and TG levels (p = 0.003), the TG-to-HDL-C ratio (p = 0.019), and the AIP value (p = 0.012) remained significant. Based on these findings, we suggest that serum YKL-40 may be a useful initial screening tool or follow-up risk indicator for lipid abnormalities, atherosclerosis, and cardiovascular disease in children and adolescents with risk factors, regardless of obesity.

Atopic dermatitis: Correlation of severity with allergic sensitization and eosinophilia.

Background: It is widely acknowledged that food sensitization is related to atopic dermatitis in infants and young children. Objective: To investigate the association of aeroallergen sensitization with increased rates and severity of atopic dermatitis in school children. Methods: We enrolled 576 children (mean age, 9.4 ± 1.8 years) from six elementary schools. Atopic dermatitis was diagnosed by questionnaires, and severity was rated by physical examinations graded by using the Scoring Atopic Dermatitis (SCORAD) index. Skin-prick tests to 22 common allergens (6 aeroallergens and 16 food allergens) were conducted. Logistic and linear regression analyses were performed by using two models: model I adjusted for age, sex, and body mass index z score; and model II adjusted for all model I factors plus asthma and allergic rhinitis. Results: We diagnosed atopic dermatitis in 22.4% (n = 129) of the children, sensitization to foods in 48.3% (n = 278), and sensitization to aeroallergens in 11.3% (n = 65). A total of 26.2% of the children (n = 149) had mild and 6.5% had moderate-to-severe symptoms and signs of atopic dermatitis (n = 37). Atopic dermatitis was associated with sensitization to aeroallergens and eosinophilia (model I), but this risk was no longer significant after additional adjustment for current allergic status (model II). However, the relationship of the total SCORAD score with aeroallergen sensitization and eosinophilia was significant in model I and model II. Conclusion: The severity of atopic dermatitis correlated with the extent of allergic sensitization and eosinophilia. Analysis of our results suggests that more sensitization to dust mites and eosinophilia are related to increased rates and high severity scores of atopic dermatitis.

Serum Periostin Level Has Limited Usefulness as a Biomarker for Allergic Disease in 7-Year-Old Children.

BACKGROUND: Previous studies have used serum periostin levels as a biomarker of Th2-driven inflammatory responses. However, no population-based study has yet examined the association of serum periostin levels with the allergic status of children. OBJECTIVES: The aim of this study was to determine the usefulness of periostin as a biomarker for allergy in a group of 7-year-old Korean children. METHOD: This prospective cross-sectional study examined 451 children (aged 7 years to 7 years and 11 months) from the general pediatric population who attended 6 different schools between June and July 2016. A total of 249 children, all of whom completed the questionnaire and skin prick test and provided blood samples, were included in the final analysis. RESULTS: The geometric mean serum periostin level was 107.6 ng/mL (95% CI 104.5-110.7). After adjustment for confounding, serum periostin levels were significantly associated with sensitization to poly-allergens (adjusted odds ratio, aOR 1.032, 95% CI 1.006-1.059, p = 0.016) and pollen (aOR 1.020, 95% CI 1.002-1.039, p = 0.026). Serum periostin levels were also associated with eosinophil levels (adjusted ß = 0.023, SE = 0.009, p = 0.010), but were unrelated to body mass index, sex, obesity, or presence of an allergic disease. CONCLUSIONS: Our results suggest thatserum periostin level may have limited usefulness as a biomarker of allergic disease in children.

Korean childhood asthma study (KAS): a prospective, observational cohort of Korean asthmatic children.

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.

Early detection of airway obstruction by impulse oscillometry system in methacholine challenge testing in preschool children.

BACKGROUND: Small airway hyperresponsiveness is a critical aspect in preschool children with asthmatic symptoms interms of asthma control. The aim of this study was to elucidate the relationship of changes in reactance (Xrs) and resistance (Rrs) of IOS and FEV1 with those in clinical parameters and to determine which IOS parameter is correlated with bronchial hyperresponsiveness before positive clinical endpoints. METHODS: We performed the methacholine challenge test in ninety-four preschool children (4.2±1.1 years) with suspected asthma. The end of test (EOT+) was defined as one or more of the following: audible wheezing (PCw+), a fall in the oxygen saturation (w92%, PCs+) or development of respiratory symptoms (PCr+). RESULTS: Mean changes in FEV1, Xrs5, and Rrs5 in the EOT+ group were 39.2±14.3% (95% CI 35.1-43.2%), 176.8±78.0 (95% CI 154.9-198.8) and 53.6±30.2 (45.1-62.0), respectively. The changes of Xrs5 in three EOT+ groups exceeded 80% and were lowest in PCr+(median, 95.9, IQR;73.4 to 132.4), followed by PCw+ and PCs+. However, Rrs5 did not show greater than 40% changes in PCr+. Xrs5 showed a higher correlation with changes in saturation (r=-0.578) than Rrs5 (r=-0.426). A49% decrease in Xrs5 was the optimal point for predicting a 80% change of Xrs5 at the following step. CONCLUSION: When examining the 5 step methacholine challenge test in preschoolers, the use of clinical parameters alone as an endpoint is of little value. The reactance value of 5 Hz is a useful predictive marker for bronchial hyperresponsiveness.

Transglutaminase 2 expressed in mast cells recruited into skin or bone marrow induces the development of pediatric mastocytosis.

BACKGROUND: Mastocytosis is characterized by a pathological increase in mast cells in organs such as skin and bone marrow. Transglutaminase 2 (TG2) expressed in mast cells contributes to allergic diseases, but its role in mastocytosis has not been investigated. This study aimed to investigate whether TG2 contributes to pediatric mastocytosis. METHODS: Serum, various skin tissues or bone marrow (BM) biopsy and aspirates were obtained from pediatric normal control or patients with indolent systemic mastocytosis (SM), mastocytoma, and urticaria pigmentosa (UP). Tryptase, individual cytokines, leukotriene C4 (LTC4 ), and TG2 activity in the serum were determined by enzyme-linked immunosorbent assay, mast cell population by May-Grünwald-Giemsa, CD 117 by immunofluorescence, cell surface molecules by Western blot, and colocalization of c-kit and TG2 or IL-10-expressing cells, CD25, and FOXP3 by immunohistochemistry. RESULTS: Infiltration of CD25(+) CD117(+) CD2(-) mast cells into BM and scalp/trunk/ear dermis; expression of FcεRI, tryptase, c-kit, FOXP3, CCL2/CCR2, and vascular cell adhesion molecule-1; and colocalization of c-kit and TG2 were enhanced in patient's skin tissues or BM, particularly SM, but colocalization of c-kit and IL-10-expressing cells was decreased vs. normal tissues. Amounts of LTC4 and inflammatory cytokines, expression of tryptase or TG2 activity were increased in patient's serum, BM aspirates, or ear/scalp skin tissues, respectively, vs. normal persons, but IL-10 level was decreased. CONCLUSION: The data suggest that mast cells, recruited in the skin and BM by CCL2/CCR, may induce the development of pediatric mastocytosis through reducing IL-10 due to upregulating TG2 activity via transcription factor nuclear factor-κB. Thus, TG2 may be used in diagnosis of pediatric mastocytosis, particularly SM.