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.

Investigating the occurrence of autoimmune diseases among children and adolescents hospitalized for Mycoplasma pneumoniae infections.

Background: Mycoplasma pneumoniae infection is common in the general population and may be followed by immune dysfunction, but links with subsequent autoimmune disease remain inconclusive. Objective: To estimate the association of M. pneumoniae infection with the risk of subsequent autoimmune disease. Methods: This retrospective cohort study examined the medical records of South Korean children from 01/01/2002 to 31/12/2017. The exposed cohort was identified as patients hospitalized for M. pneumoniae infection. Each exposed patient was matched with unexposed controls based on birth year and sex at a 1:10 ratio using incidence density sampling calculations. The outcome was subsequent diagnosis of autoimmune disease, and hazard ratios (HRs) were estimated with control for confounders. Further estimation was performed using hospital-based databases which were converted to a common data model (CDM) to allow comparisons of the different databases. Results: The exposed cohort consisted of 49,937 children and the matched unexposed of 499,370 children. The median age at diagnosis of M. pneumoniae infection was 4 years (interquartile range, 2.5-6.5 years). During a mean follow-up time of 9.0 ± 3.8 years, the incidence rate of autoimmune diseases was 66.5 per 10,000 person-years (95% CI: 64.3-68.8) in the exposed cohort and 52.3 per 10,000 person-years (95% CI: 51.7-52.9) in the unexposed cohort, corresponding to an absolute rate of difference of 14.3 per 10,000 person-years (95% CI: 11.9-16.6). Children in the exposed cohort had an increased risk of autoimmune disease (HR: 1.26; 95% CI: 1.21-1.31), and this association was similar in the separate analysis of hospital databases (HR: 1.25; 95% CI 1.06-1.49). Conclusion: M. pneumoniae infection requiring hospitalization may be associated with an increase in subsequent diagnoses of autoimmune diseases.

Association of Serum Vitamin D Level with Temporomandibular Disorder Incidence: A Retrospective, Multi-Center Cohort Study Using Six Hospital Databases.

The relationship between serum vitamin D levels and temporomandibular disorders (TMDs) remains unclear. Therefore, this study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) levels and TMD incidence using large-scale health data. Clinical data from the electronic health records of six secondary or tertiary hospitals in Korea were used to evaluate the relationship between serum 25(OH)D levels and TMD incidence. The data were converted to the Observational Medical Outcomes Partnership Common Data Model. A cohort study was designed using the Cox proportional hazards model to examine the hazard ratio (HR) of TMD development after propensity score matching (PSM). An aggregate meta-analysis of the HR was subsequently performed. After 1:4 PSM, a target group with deficient 25(OH)D levels (<20 ng/mL) (N = 34,560) and comparator group with non-deficient 25(OH)D levels (≥20 ng/mL) (N = 47,359) were pooled from six hospital databases. HR meta-analysis demonstrated a significant association between deficient 25(OH)D levels and TMD incidence (pooled HR: 1.50; 95% confidence interval: 1.07-2.12). In conclusion, deficient 25(OH)D levels were found to be associated with an increased TMD risk. Therefore, vitamin D deficiency is a potential risk factor for TMD development.

Infant Feeding Pattern Clusters Are Associated with Childhood Health Outcomes.

(1) Background: Feeding behavior habits have a pattern with a certain tendency during infancy. We aimed to identify the associations between feeding patterns in infancy and the subsequent 10-year childhood disease burden. (2) Methods: Data from 236,372 infants were obtained from the national health insurance and screening program records in South Korea. Parent-administered questionnaires during infancy provided details on the feeding type and types/frequency of complementary food for analyzing feeding patterns. The outcomes were all-cause hospitalization and the development of 15 representative childhood diseases until the age of 10 years. Anthropometric measurements obtained at 6 years of age were analyzed. To estimate outcome risks while considering multiple risk factors, we employed a Cox proportional hazard and modified Poisson regression. (3) Results: Three clusters were identified: high prevalence of breastfeeding with regular exposure to a variety of solid foods (n = 116,372, cluster 1), similar prevalence of breastfeeding and formula feeding with less exposure to solid foods (n = 108,189, cluster 2), and similar prevalence of breastfeeding and formula feeding with the least exposure to solid foods in infancy (n = 11,811, cluster 3). Compared with cluster 1, children in clusters 2 and 3 had increased risks of all-cause hospitalization (hazard ratio (HR), (95% confidence interval (CI)), 1.04 (1.03-1.06) and 1.08 (1.05-1.11), respectively). Children in clusters 2 and 3 had an increased risk of upper respiratory infection, pneumonia, and gastroenteritis, as well as neurobehavioral diseases. Overweight/obesity at the age of 6 years was associated with clusters 2 and 3. (4) Conclusions: Feeding patterns in infancy were associated with an increased risk of childhood disease burden.

Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease.

Importance: Rotavirus infection is a common cause of gastroenteritis in children that can trigger autoimmune processes, but the nature of this interaction remains poorly understood. Objective: To estimate the association of rotavirus infection with the risk of subsequent autoimmune disease. Design, Setting, and Participants: This population-matched cohort study used data from children and adolescents (aged younger than 18 years) in South Korea (national registers from January 1, 2002, to December 31, 2017). The cohort consisted of 86 157 patients in the exposure group who had experienced rotavirus-associated hospitalization and the same number of matched patients in the unexposed group. Data analyses were from May 1, 2020, through October 20, 2022. Exposures: Hospitalization for rotavirus infection. Main Outcomes and Measures: The main outcome was childhood autoimmune diseases during the study defined by diagnoses according to the National Health Insurance Database. Hazard ratios (HRs) with 95% CIs for autoimmune diseases were estimated using a Cox model, with multiple confounding factors controlled. Results: This cohort study consisted of 1 914 461 individuals born in South Korea from 2002 to 2005 who were potentially eligible. After exclusions, there were 86 517 individuals in the exposed group and 86 517 in the unexposed group after 1:1 incidence density sampling. The study included 49 072 (57.0%) male patients. The median (IQR) age at diagnosis of rotavirus-associated hospitalization was 1.5 (0.9-2.7) years, and the HR for autoimmune disease in the exposed group was 1.24 (95% CI, 1.19-1.28) for a mean (SD) follow-up time of 12.1 (3.2) years. The use of more stringent definitions for exposure and outcomes in a multivariable stratified analysis also indicated that rotavirus-associated hospitalization was associated with an increased risk of subsequent autoimmune disease (HR, 1.22 [95% CI, 1.16-1.28]). Sensitivity analysis showed that individuals with rotavirus-associated hospitalization was related to multiple autoimmune syndromes (2 or more: HR, 1. 51 [95% CI, 1. 31-1. 73]; 3 or more: HR, 1. 79 [95% CI, 1.18-2.72]) and that the number of rotavirus-associated hospitalization were associated with higher risks for autoimmune disease in a dose-dependent manner (single hospitalization event: HR, 1.20 [95% CI, 1.16-1.24]; multiple events HR, 1.60 [95% CI, 1.49-1.72]). Conclusions and Relevance: Our results indicate that rotavirus-associated hospitalization is significantly associated with subsequent autoimmune disease during childhood. Clinicians should be aware of the heightened susceptibility to autoimmune disease in individuals with prior rotavirus-associated hospitalization.

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.

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.

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.

Association of Antibiotic Use during the First 6 Months of Life with Body Mass of Children.

In this study, our objective was to assess the association of body mass in preschool children with the use of antibiotics within 6 months after birth. National administrative databases were used to examine all children born between 2008 and 2009 in Korea. Exposure was defined as the use of systemic antibiotics during the first 6 months of age. The observed outcomes were stunting (height for age [HFA] z score < −2.0), short stature (HFA z score < −1.64), overweight (body mass index [BMI] for age z score ≥ 1.04), and obesity (BMI for age z score ≥ 1.64), and the children's height and body weight were measured from three to six years of age. To balance characteristics between the antibiotic user and non-user groups, propensity score matching was performed. The outcomes were evaluated using a generalized estimation equation with the logit link function. Analysis of antibiotic use by children during the first 6 months of life indicated there were 203,073 users (54.9%) and 166,505 non-users (45.1%). After PS matching, there were 72,983 antibiotic users and 72,983 non-users. Antibiotic use was significantly associated with stunting (aOR = 1.198, 95% CI = 1.056 to 1.360) and short stature (aOR = 1.043, 95% CI = 1.004 to 1.083), and had significant negative association with HFA z score (weighted ß = −0.023). The use of an antibiotic for 14 days or more had a marked association with stunting. Antibiotic use was also associated with overweight, obesity, and increased BMI for age z score. Antibiotic use during the first 6 months of life increased the risk of stunting, short stature, overweight, and obesity in preschool children.

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.

Association of Consuming Tap Water or Purified Water during Infancy with Irritable Bowel Syndrome in Children.

OBJECTIVE: The objective of this study was to analyze the effect of consuming formula powder prepared with tap water or purified water during the first 4 to 6 months of life on the subsequent development of irritable bowel syndrome (IBS). STUDY DESIGN AND SETTING: A total of 917,707 children who were born in Korea between 2007 and 2008 were analyzed. All children were followed up until they lost eligibility for health care services or until 2017. Data on the water used to prepare formula powder were from questionnaires answered by the parents when the child was 4 to 6 months old. IBS was defined as two or more diagnoses of IBS after the age of 4 years. Inverse probability of treatment weighting (IPTW) using the propensity score was used to balance the two groups. The risk of IBS was evaluated using a Cox proportional hazards model. RESULTS: After weighting, there were 73,355 children in the tap water group and 73,351 in the purified water group. The purified water group had a higher risk of IBS (HR: 1.05; 95% CI: 1.01, 1.09). This relationship was also present after the subgroup analyses of males and females and the sensitivity analysis that used different definitions of IBS. CONCLUSIONS: Drinking formula powder prepared with purified water rather than tap water during the first 4 to 6 months of age was found to be associated with IBS.

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.

Molecular sensitization patterns in birch pollen-sensitized Korean children according to the presence of oral allergy syndrome.

The profiles of sensitization based on component-resolved diagnosis (CRD) differ from region to region in populations sensitized to birch pollen. We investigated the endotypes of birch pollen-sensitized Korean children with allergic diseases using CRD and distinguished the endotypes of oral allergy syndrome (OAS) among them.Thirty-one birch pollen-sensitized children with allergic diseases were enrolled. Specific immunoglobulin E (IgE) to birch pollen and fruit including apple, peach, and kiwi were evaluated via skin prick tests and ImmunoCAP in all subjects. Sensitization profiles based on CRD were evaluated with the Immuno-solid-phase Allergen Chip for birch pollen-sensitization using birch pollen components (Bet v 1, Bet v 2, and Bet v 4), and for OAS using the allergen families pathogenesis-related class 10 proteins (PR-10), lipid transfer proteins, and profilin.All patients (n = 13) with OAS were sensitive to Bet v 1. However, 61% (11/18) of patients without OAS were sensitized to Bet v 1. The level of specific IgE to Bet v 1 was higher in patients with OAS than in those without OAS. All birch pollen-sensitized Korean children with OAS were sensitized to PR-10, and 69% (9/13) of them were mono-sensitized to PR-10. Among patients without OAS, 33% (6/18) were not sensitized to any of the allergen families.Birch pollen-sensitized Korean children with allergic diseases showed unique patterns of sensitization to Bet v 1, Bet v 2, and Bet v 4, and the sensitization profiles based on CRD were totally different according to the presence of OAS.

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 levels of periostin and exercise-induced bronchoconstriction in asthmatic children.

BACKGROUND: Periostin is induced by IL-13 and has been studied as a biomarker of asthma. The present study explored the relationship between serum levels of periostin and exercise-induced bronchoconstriction (EIB) in asthmatic children. METHODS: The study population consisted of 86 children 6-15 years old divided into an asthmatic group (n = 56) and healthy controls (n = 30). We measured the levels of periostin in serum and performed pulmonary function tests including baseline measurements, post-bronchodilator inhalation tests, exercise bronchial provocation tests (BPTs), and mannitol BPTs. RESULTS: The 56 asthmatic children were divided into four groups: asthmatics with positive exercise BPT and positive mannitol BPT (n = 30), asthmatics with positive exercise BPT but negative mannitol BPT (n = 7), asthmatics with negative exercise BPT but positive mannitol BPT (n = 10), and asthmatics with negative exercise BPT and negative mannitol BPT (n = 9). Serum levels of periostin in asthmatic children with both positive exercise and mannitol BPT were significantly greater than those in asthmatic children with both negative exercise and mannitol BPT (95.0 [75.0-104.0] vs. 79.0 [68.0-82.5] ng/mL, P = 0.008) and controls (74.0 [69.75-80.0] ng/mL, P < 0.001). Periostin levels were significantly correlated with both the maximum decrease in %FEV1 and mannitol PD15 value. CONCLUSION: Serum levels of periostin in asthmatic children with both positive exercise and mannitol BPT were significantly greater than those in asthmatic children with both negative exercise and mannitol BPT and also greater than in healthy controls.

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.

Serum Periostin Is Negatively Correlated With Exposure to Formaldehyde and Volatile Organic Compounds in Children.

Epidemiological studies have shown that exposure to tobacco smoke causing irritation and inflammation in the airways tends to reduce serum periostin concentrations in adults. We now investigate prospective cross-sectional study on 135 Korean students aged 7 years in the first grade who were participating in the Seongnam Atopy Project for Children's Happiness 2016 (SAP2016) cohort. To the best of our knowledge, this is the first study to show significant inverse correlations between serum periostin concentration and exposure to xylene and formaldehyde in children. Our findings suggested the need for caution in using the serum periostin level as a marker for allergic diseases, since exposure to volatile organic compounds and formaldehyde may confound the interpretation of these results.

Exhaled nitric oxide and mannitol test to predict exercise-induced bronchoconstriction.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is diagnosed via exercise challenge on a treadmill, but such testing requires complex equipment and sufficient health-care resources. The fraction of exhaled nitric oxide (FeNO) test and mannitol bronchial provocation test (BPT) may serve as a surrogate for exercise testing. METHODS: We compared the diagnostic utilities of the FeNO test and mannitol BPT in predicting EIB in asthmatic children. We retrospectively analyzed data from 60 asthmatic children aged 6-16 years. We compared the exercise BPT results, FeNO levels, and mannitol BPT data. RESULTS: All subjects were divided into exercise-positive (n = 41) or -negative (n = 19) BPT groups. Of the 41 exercise-positive patients, 32 were mannitol BPT positive and nine were mannitol BPT negative. Of the 19 exercise-negative patients, nine and 10, respectively, were mannitol BPT positive and BPT negative. The maximum % forced expiratory volume in 1 s (FEV1 ) decrease after exercise was positively correlated with FeNO (r = 0.556, P < 0.001), and with mannitol response-dose ratio (RDR; r = 0.416, P = 0.001). The receiver operating characteristic (ROC) curve for FeNO to discriminate between asthmatic subjects with and without EIB had an area under the curve (AUC) of 0.771 (95%CI: 0.643-0.870). The discriminatory ROC curve for mannitol RDR had an AUC of 0.763 (95%CI: 0.633-0.864). The AUC of FeNO and mannitol RDR did not differ significantly. CONCLUSIONS: EIB significantly correlated with both FeNO and mannitol BPT data. Given that both methods similarly predicted EIB in asthmatic children, the simpler and safer FeNO test alone may be a clinically useful diagnostic tool.

Prevalence and Clinical Characteristics of Local Allergic Rhinitis in Children Sensitized to House Dust Mites.

OBJECTIVE: The prevalence of local allergic rhinitis (LAR) in nonatopic children remains unknown. This study aimed to determine the prevalence, clinical characteristics, and severity of LAR in children in comparison to classical allergic rhinitis (AR) and nonallergic rhinitis (NAR). STUDY DESIGN: A total of 145 children (aged 1-18 years) were enrolled and classified into 3 groups (AR, NAR, and LAR) based on a skin prick test (SPT) and a nasal provocation test (NPT) with house dust mite, i.e., Dermatophagoides pteronyssinus. NPT positivity was defined as a symptom score ≥2 standard deviations (SDs) above the healthy control score. RESULTS: Eighty-one children had AR (55.9%), and 64 (44.1%) had symptoms of rhinitis with negative SPT; 59 NAR (40.7%) and 5 LAR (3.4%) children were identified. The κ score for agreement between the SPT and the NPT results was 0.778 (95% CI 0.726-0.830, p < 0.001). A significant correlation was observed between wheal diameter and maximum nasal symptom score provoked by D.pteronyssinus (rho = 0.589, p < 0.001). Nasal severity according to the ARIA guideline did not show any differences in the 3 groups (p = 0.693). The AR group was older than the LAR and NAR groups (AR > LAR > NAR, p = 0.003). CONCLUSIONS: Despite the evidence to support the existence of LAR in pediatric populations, we found that its prevalence was relatively low, possibly due to the high rate of agreement between SPT and NPT. Further investigations are needed to identify immunological as well as clinical implications of LAR.