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BACKGROUND AND OBJECTIVE Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age-related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children. METHODS Spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%-75%) and clinical information were gathered from three population-based birth cohorts. Predicted GLI reference values and z scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z scores were compared with the expected 0 and 1. Probabilities of falling below the lower limit of normal (LLN) (z score: -1.64) were compared with the expected value 5%. GLI z scores were assessed according to low ( 2) BMI z score groups. RESULTS Mean z scores significantly differed from 0 for FEV1/FVC in males (mean [95% confidence interval]: 0.18 [0.08, 0.27]) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in females (-0.23 [-0.31, -0.15] and -0.26 [-0.36, -0.16], respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5% for FEV1 (12.13% [9.64, 14.77]), FVC (15.86% [13.06, 18.81]), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) (7.31% [5.29, 9.49]) in males and FVC (11.91% [9.40, 14.60]) in females. FEV1 and FVC z scores increased across low to high body mass index (BMI) groups, and FEV1/FVC decreased from low to high BMI groups. CONCLUSION GLI equations marginally differ from real-world values, which should be considered by pulmonologists in practice or research.

Objective The loudness dependence of the auditory evoked potential (LDAEP) is a reliable indicator that is inversely related to central serotonergic activity, and recent studies have suggested an association between LDAEP and suicidal ideation. This study investigated differences in LDAEP between patients with major depressive disorder and high suicidality and those with major depressive disorder and low suicidality compared to healthy controls. Methods This study included 67 participants: 23 patients with major depressive disorder with high suicidality (9 males, mean age 29.3 ± 15.7 years, total score of SSI-BECK ≥ 15), 22 patients with major depressive disorder with low suicidality (9 males, mean age 42.2 ± 14.4 years, total score of SSI-BECK ≤ 14), and 22 healthy controls (11 males, mean age 31.6 ± 8.7 years). Participants completed the following assessments: Patient Health Questionnaire-9, Beck Depression Inventory-II, Beck Scale for Suicidal ideation, State Anxiety Scale of the State-Trait Anxiety Inventory, Beck Anxiety Inventory, and LDAEP (measured at electrode Cz). Results There were no sex-related differences among groups (p = 0.821). The high-suicidality group exhibited significantly higher LDAEP compared to the low-suicidality group (0.82 ± 0.79 vs. 0.26 ± 0.36, p = 0.014). No significant differences were found between the control and high-suicidality (p = 0.281) or the control and low-suicidality groups (p = 0.236). Conclusion LDAEP was applied to demonstrate the association between serotonergic activity and suicidal ideation and suicide risk in major depression and may be a candidate of biological marker for preventing suicide in this study.

Suicide is the leading cause of death among adolescents in South Korea, and depression and personality profiles have been identified as significant risk factors for self-injurious behavior. This study examined the influence of depressive mood and temperament/ character on self-injury in adolescents.A total of 116 adolescents (aged 12-18 years) with a primary diagnosis of major depressive disorder (MDD) and their parents were enrolled in this study. The participants were divided into three groups based on adolescent's self-injury frequency, and their Children's Depression Inventory (CDI), Youth Self-Report (YSR), and Temperament and Character Inventory (TCI) scores were compared. Finally, mediation analysis was conducted to investigate the relationship between suicidal ideation and self-injury.Of study participants, 75.9% answered that they had suicidal ideation, and 55.2% answered that they had engaged in self-injurious behavior in the last six months. There were significant differences in CDI and suicidal ideation among the groups. After adjusting for age and sex, mediation analysis indicated that depressive mood mediated the relationship between suicidal ideation and self-injury.This study emphasizes the importance of evaluating and managing depressive mood severity in adolescents with MDD as these factors partially mediate the transition from suicidal ideation to self-injury.

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.

Adverse drug events are significant causes of emergency department visits. Systematic evaluation of adverse drug events leading to emergency department visits by age is lacking. This multicenter retrospective observational study evaluated the prevalence and features of adverse drug event-related emergency department visits across ages. We reviewed emergency department medical records obtained from three university hospitals between July 2014 and December 2014. The proportion of adverse drug events among total emergency department visits was calculated. The cause, severity, preventability, and causative drug(s) of each adverse drug event were analyzed and compared between age groups (children/adolescents [

Background The global burden of seasonal influenza on medical care has been one of the greatest in the pediatric population. The attention drawn to influenza B was relatively low compared to influenza A, probably because the influenza B virus was thought to be less virulent and have a lower pandemic potential. This study aimed to compare the clinical features of influenza A and B in children. Methods This retrospective study included children diagnosed and treated for influenza as inpatients or outpatients during the 2017/18 influenza season at a tertiary referral hospital. Data regarding clinical characteristics, diagnoses, laboratory results, and vaccination histories were collected and reviewed. Results Over the study period, 128 patients with influenza A and 109 patients with influenza B were identified. The mean age of patients with influenza B was significantly higher than that of patients with influenza A (5.6 ± 4.4 vs 4.1 ± 4.4 years, p = 0.010). Fever was the most common manifestation of influenza followed by respiratory symptoms. No single symptom was specifically associated with either type of influenza. The total duration of fever (4.3 ± 2.3 vs 3.7 ± 2.6 days), ‘time from fever onset to initiation of antivirals’, and ‘time from initiation of antivirals to defervescence’ were similar between the two influenza types, even though all three time periods tended to be longer for influenza B. The platelet counts and proportions of neutrophils were higher for influenza A than for influenza B infections, although the values were within normal limits for both influenza types. Conclusions We found overall clinical similarities between influenza A and B with no less clinical significance or severity of influenza B compared to those of influenza A. Equal levels of awareness and attention should be paid to both influenza types.

Highlights • Five (1.22%) influenza C viruses were detected in 409 RV16 test negative samples during the influenza season. • Young children are infected with influenza C virus and are at risk for acute respiratory illness. • C/Sao Paulo/387/82-like lineage viruses circulated in South Korea. • Re-assortment event was observed in the C/Seoul/APD462/2015 strain., Background Influenza C virus has been largely neglected, compared to influenza A orB viruses, and is not routinely tested in clinical practices. However, several studies have indicated that influenza C virus causes severe acute respiratory illness and pneumonia in all ages. Objective We conducted a study to identify influenza C virus among young children in South Korea.Study design. From October 2013 to September 2016, 973 young children with influenzalike illness (ILI) were enrolled at three university hospitals. We tested nasopharyngeal samples for 16 types of respiratory viruses. Among the tested samples, 564 were positive for one or more respiratory viruses. Except for the samples where 16 types of respiratory viruses were found, 409 negative samples were examined for the presence of influenza C virus, using a matrix gene specific primer set. Results Among 409 nasopharyngeal samples, five influenza C viruses were detected. The manifestation of influenza C virus infection in young children was observed acute respiratory illness, such as fever, rhinorrhea, and cough, but no pneumonia or severe respiratory illness. Nucleotide sequencing was conducted and a phylogenetic tree was generated. We found that C/Sao Paulo/387/82-like lineage viruses circulated in South Korea, and the fully sequenced virus (C/Seoul/APD462/2015) was closely related to C/Victoria/2/2012 and C/Tokyo/4/2014 strains. Conclusions This study was the first report of influenza C virus detection in South Korea. Although severe illness was not observed in this study, we suggest the necessity for influenza C virus testing in pediatric patients with ILI, considering other reports of severe illnesses caused by influenza C virus infections.

Although bronchial responsiveness (BR) is usually categorized as normal or hyperresponsive to aid the diagnosis of asthma, it exists on a continuous spectrum, not in a dichotomous manner. We aimed to evaluate the distribution profile of BR in a general population of 7-year-olds.In 2015, 7-year-old Korean children from a nationwide birth cohort study visited regional study hospitals for skin prick test, standard spirometry, and bronchial provocation to establish reference values for the general population. Their BR degrees were categorized into five ordered groups: hyperresponsive BRs were classified into group 1 (provocative concentration (PC) of methacholine causing a 20% fall in forced expiratory volume in 1 second [FEV1], PC20 of4 mg/mL) and group 2 (PC20 of ≥4 mg/mL and16 mg/mL), and nonresponsive BRs were categorized into group 3 (final FEV1 percentage fall after inhaling 16 mg/mL of methacholine [FEV1%fall] of15% and ≤20%), group 4 (FEV1%fall of10% and ≤15%), and group 5 (FEV1%fall of ≤10%).In total, 559 subjects finished all tests reliably. Groups 1 and 2 comprised 10.0% and 15.7% of the total population, respectively. Groups 3, 4, and 5 comprised 14.7%, 18.4%, and 41.1%, respectively. As the group number increased, the proportion of those with recent wheezing and those with indoor allergen sensitization decreased (P for trend = 0.001 and P for trend 0.001, respectively), and the baseline FEV1/FVC increased (P for trend 0.001) CONCLUSION: BR of the 7-year-olds in the general population, while showing a wide distribution across phenotypes, is associated with allergic symptoms, negatively correlated with baseline lung function and positively correlated with indoor allergen sensitization.

Recurrent bacterial infection causes frequent bronchiectasis (BE) exacerbations. The effectiveness and safety of long-term administration of macrolides in BE remain controversial, especially in children who require minimal treatment to prevent exacerbation. We conducted this meta-analysis to determine the usefulness of long-term macrolide use in pediatric BE. We searched PubMed, Cochrane Library databases, Embase, KoreaMed, Igaku Chuo Zasshi, and Chinese National Knowledge Infrastructure databases. We identified randomized controlled trials (RCTs) which elucidated long-term macrolide treatment (≥ 4 weeks) in non-cystic fibrosis BE in children aged

Background: This study aimed to present the development process and characteristics of the Korean Registry of Acute Myocardial Infarction for Regional Cardiocerebrovascular Centers (KRAMI-RCC). Methods: We developed KRAMI-RCC, a web-based registry for patients with AMI. Patients from 14 RCCs were registered for more than three years from July 2016. It includes an automatic error-checking system, and user training and on-site monitoring are performed to manage data quality. Results: A total of 11,700 AMI patients were registered in KRAMI-RCC over three years (73.9% men). The proportions of patients with ST-elevation and non-ST-elevation myocardial infarction at discharge were 43.4% and 56.6%, respectively. Of the total three-year patients, 5.6% died in the hospital, and 4.4% died 12 months after discharge. The case fatality within 12 months was 9.7%. Pre-hospital care data showed delayed arrival time after onset of symptoms (median 153 min) and low transportation rate by public ambulance (25.2%). Post-hospital care data showed lower participation rate in the second rehabilitation program (16.8%). Conclusions: The recently developed KRAMI-RCC registry has been more focused on pre-hospital and post-hospital data, which will be helpful in understanding the current state of AMI disease management and in making policy decisions to reduce case fatality in Korea.

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.

We aimed to characterize the lineages of influenza B viruses obtained from clinical specimens during the 2007-2014 seasons in South Korea. RT-PCR for the partial hemagglutinin gene of influenza B virus was performed on laboratory-confirmed influenza B samples from the 2007-2008 season to 2013-2014 season. A phylogenetic tree was generated, and current influenza vaccine strains for the Northern Hemisphere were used as representative strains of Victoria and Yamagata lineages. A total of 571 influenza B virus sequences were analyzed. During the 2009-2010 season, most of the circulating influenza B viruses matched the vaccine strain; 91.0% (91/100) of viruses belonged to the Victoria lineage. In the 2007-2008, 2011-2012, and 2013-2014 seasons, co-circulation of each influenza B lineage was found with a match ratio to the vaccine strain of 53.2% (42/79), 40.9% (63/154), and 58.3% (134/230), respectively. Overall, 41.7% (238/571) of the circulating influenza B viruses belonged to the lineage mismatching the vaccine strain. During the seven influenza seasons, influenza B epidemics were substantial in four seasons in South Korea. Significant mismatches of the vaccine and lineage of the circulating influenza B viruses were found. The current trivalent influenza vaccine may not be fully suitable for effective protection against influenza B.

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.

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.

Over 3000 candidate gene association studies have been performed to elucidate the genetic underpinnings of schizophrenia. However, a comprehensive evaluation of these studies’ findings has not been undertaken since the decommissioning of the schizophrenia gene (SzGene) database in 2011. As such, we systematically identified and carried out random-effects meta-analyses for all polymorphisms with four or more independent studies in schizophrenia along with a series of expanded meta-analyses incorporating published and unpublished genome-wide association (GWA) study data. Based on 550 meta-analyses, 11 SNPs in eight linkage disequilibrium (LD) independent loci showed Bonferroni-significant associations with schizophrenia. Expanded meta-analyses identified an additional 10 SNPs, for a total of 21 Bonferroni-significant SNPs in 14 LD-independent loci. Three of these loci (MTHFR, DAOA, ARVCF) had never been implicated by a schizophrenia GWA study. In sum, the present study has provided a comprehensive summary of the current schizophrenia genetics knowledgebase and has made available all the collected data as a resource for the research community.

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.

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.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune regulation. HLH consists of two forms: familial and acquired, the latter which occurs in association with infection, malignancy, rheumatic disease and acquired immune deficiency. Herein, we report a case of acquired HLH in a child who had received allogeneic hematopoietic stem cell transplantation for familial HLH with UNC13D mutation. Based on microbiology, only rotavirus was identified as a possible organism triggering HLH. The patient's fulminant clinical course included acute respiratory failure, a sepsis-like pattern, disseminated intravascular coagulopathy, and rhabdomyolysis, leading to multiorgan failure and death from septic shock.

Purpose Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. Methods We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. Results The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77-15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40-40.74). Conclusions Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Background The incidence of asthma exacerbation (AE) and the predictive value of spirometry and fractional exhaled nitric oxide (FeNO) in school children have not been evaluated. Objective We sought to evaluate the efficacy of spirometry measurement and FeNO monitoring for predicting AE in school children in the Cheongju area in Korea. Methods With parental agreement, we studied 170 students aged 7–12 years. Children were evaluated by an asthma specialist using baseline spirometry, skin prick test, seasonal FeNO measurement, and asthma control test. The study participants underwent a physical examination and their medical history was also evaluated by the specialist. They were assessed for asthma control status during regular doctor visits for 1 year. Results In total, 160 children (94.1%) completed follow-up and FeNO monitoring. Of which, 26 children (16.3%) had AE. AE was associated with male children and children with allergic rhinitis (p < 0.05). While, children with AE tended to have higher FeNO than those without AE, no significant difference was found. The maximum value of FeNO ≥35 ppb was associated with AE (p < 0.05). Children with AE had a significantly decreased baseline forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), %predicted, forced expiratory flow at 25%–75% of FVC (FEF25%–75%). FEV1/FVC < 80% was associated with AE in children regardless of inhalant allergen sensitization (all p < 0.05). Conclusion Baseline spirometry had a predictive value of AE in school children. Sensitive spirometric parameters such as FEV1/FVC and FEF25%–75% can be used as prognostic factors to predict future childhood AE. FeNO value ≥ 35 ppb during monitoring was associated with AE in school children.

Purpose: It is controversial whether indoor pet exposure is either a risk or protective factor developing sensitization to pet allergens or asthma. Therefore, we investigated whether indoor pet ownership entails a risk for the development of asthma and sensitization in childhood. Methods: The Panel Study of Korean Children (PSKC) is a general-population-based birth cohort study that recruited 2,078 mother-baby dyads in Korea between April and July of 2008. Among 1,577 children who were followed up in 2015, 559 underwent skin prick tests, spirometry and bronchial provocation tests using Provocholine. Having a cat or a dog and the prevalence of asthma were evaluated by using self-reported questionnaires and physicians’ medical records. Results: During infancy, the rate of dog ownership was 4.5% (71 of 1,574) and that of cat ownership was 0.5% (8 of 1,574). Of the subjects, 7.9% (n=109) currently had at least 1 dog and 2.5% (n=34) had at least 1 cat. Pet ownership during infancy was associated with sensitization to cats or dogs (adjusted odds ratio [aOR], 4.24; 95% confidence interval [CI], 1.29-13.98), wheezing within 12 months (aOR, 5.56; 95% CI, 1.65-18.75) and current asthma (wheezing episode in the last 12 months+diagnosed asthma by physi cians) (aOR, 6.36; 95% CI, 1.54-26.28). In contrast, pet ownership during the last 12 months was not associated with sensitization to cats or dogs or current asthma. Conclusion: Indoor pet exposure during infancy can be critical for developing sensitization to cats or dogs and asthma in childhood. Avoidance of pet exposure in early life may reduce sensitization to cats or dogs and development of asthma. (Allergy Asthma Respir Dis 2019;7:99-105)

BACKGROUND: J waves are associated with increased vagal activity in patients with idiopathic ventricular fibrillation in several studies to date. However, the relationship between J waves and autonomic nervous activity in patients without structural heart disease remains under investigation. We investigated whether the presence of a J wave on the surface electrocardiogram (ECG) was related to increased vagal activity in patients without structural heart disease. METHODS: This retrospective study included 684 patients without structural heart disease who had undergone Holter ECG and surface ECG monitoring. Based on the presence of J waves on the surface ECG, patients were divided into two groups: those with J waves (group 1) and those without J waves (group 2). We compared heart rate variability (HRV), reflecting autonomic nervous activity, using 24‐h Holter ECG between the groups. RESULTS: J waves were present in 92 (13.4%) patients. Heart rate (HR) in group 1 was significantly lesser than that in group 2 (P = 0.031). The ratio of low‐frequency (LF) components to high‐frequency (HF) components (LF/HF) in group 1 was significantly lower than that in group 2 (P = 0.001). The square root of the mean squared differences of successive NN intervals in group 1 was also significantly higher than that in group 2 (P = 0.047). In a multivariate regression analysis, male sex, HR, and LF/HF ratio remained independent determinants for the presence of J waves (P = 0.039, P = 0.036, and P < 0.001, respectively). CONCLUSION: In patients without structural heart disease, the presence of a J wave was associated with a slow HR, male sex, and increased vagal activity, independently.

Schizophrenia is regarded as a multifactorial and polygenic brain disorder that is attributed to different combinations of genetic and environmental risk factors. Recently, several genome-wide association studies (GWASs) of schizophrenia have identified numerous risk factors, but the replication results remain controversial and ambiguous. To identify schizophrenia susceptibility loci in the Korean population, we performed a GWAS using the Illumina HumanOmni1-Quad V1.0 Microarray. We genotyped 1,140,419 single nucleotide polymorphisms (SNPs) in 350 Korea schizophrenia patients and 700 control subjects, and approximately 620,001 autosomal SNPs were passed our quality control. In the case-control analysis, the rs9607195 A>G on intergenic area 250 kb away from the ISX gene and the rs12738007 A>G on the intron of the MECR gene were the most strongly associated SNPs with the risk of schizophrenia (P = 6.2 × 10(-8) , OR = 0.50 and P = 3.7 × 10(-7) , OR = 2.39, respectively). In subsequent fine-mapping analysis, 6 SNPs of MECR were genotyped with 310 schizophrenia patients and 604 control subjects. The association of the MECR rs12738007, a top ranked-SNP in GWAS, was replicated (P = 1.5 × 10(-2) , OR = 1.53 in fine mapping analysis, P = 1.5 × 10(-6) , OR = 1.90 in combined analysis). The identification of putative schizophrenia susceptibility loci could provide new insights into genetic factors related with schizophrenia and clues for the development of diagnosis strategies.

Purpose Schizophrenia is a devastating mental disorder and is known to be affected by genetic factors. The chromogranin B (CHGB), a member of the chromogranin gene family, has been proposed as a candidate gene associated with the risk of schizophrenia. The secretory pathway for peptide hormones and neuropeptides in the brain is regulated by chromogranin proteins. The aim of this study was to investigate the potential associations between genetic variants of CHGB and schizophrenia susceptibility. Materials and methods In the current study, 15 single nucleotide polymorphisms of CHGB were genotyped in 310 schizophrenia patients and 604 healthy controls. Results Statistical analysis revealed that two genetic variants (non-synonymous rs910122; rs2821 in 3'-untranslated region) were associated with schizophrenia [minimum p=0.002; odds ratio (OR)=0.72], even after correction for multiple testing (p(corr)=0.02). Since schizophrenia is known to be differentially expressed between sexes, additional analysis for sex was performed. As a result, these two genetic variants (rs910122 and rs2821) and a haplotype (ht3) showed significant associations with schizophrenia in male subjects (p(corr)=0.02; OR=0.64), whereas the significance disappeared in female subjects (p>0.05). Conclusion Although this study has limitations including a small number of samples and lack of functional study, our results suggest that genetic variants of CHGB may have sex-specific effects on the risk of schizophrenia and provide useful preliminary information for further study.

Hea Lin Oh, Young Yull Koh, Dong In Suh, Byoung-Chul Kang, Bong-Seong Kim, Woo Kyung Kim, Jakyoung Kim, Jin Tack Kim, Hyo-Bin Kim, Geunhwa Park, Heysung Baek, Dae Jin Song, Mee Yong Shin, Hyeon-Jong Yang, Sung-Il Woo, Young Yoo, Jinho Yu, So-Yeon Lee, Dae Hyun Lim Department of Pediatrics, Seoul National University College of Medicine, Seoul; Seoul Medical Book and Publishing, Jeju; Department of Pediatrics, GangNeung Asan Hospital, University of Ulsan College of Medicine, Gangneung; Department of Pediatrics, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul; Department of Pediatrics, Kangwon National University School of Medicine, Chuncheon; Department of Pediatrics, The Catholic University of Korea College of Medicine, Seoul; Department of Pediatrics, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul; Department of Pediatrics, Gwanghye General Hospital, Busan; Department of Pediatrics, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul; Department of Pediatrics, Korea University College of Medicine, Seoul; Department of Pediatrics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon; Department of Pediatrics, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul; Department of Pediatrics, Chungbuk National University College of Medicine, Cheongju; Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul; Department of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang; Department of Pediatrics, Inha University School of Medicine, Incheon, Korea