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.

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.

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.

Eosinophil-derived neurotoxin: An asthma exacerbation biomarker in children.

Background: Asthma is a heterogeneous disease, characterized by chronic airway inflammation. Asthma exacerbations (AE) are episodes characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing, or chest tightness with a decrease in lung function. There have been previous studies that examined the role of eosinophil-derived neurotoxin (EDN) in asthma, but there have been no studies of the role of EDN in children experiencing AE. Objective: In this study, we aimed to examine the association of EDN with lung function and prognosis in children admitted for severe AE. Methods: We enrolled 82 children who were admitted for severe AE at two different university hospitals in South Korea between January 2018 and December 2019. Blood tests, including white blood cell count, myeloperoxidase (MPO), total eosinophil count, EDN, C-reactive protein (CRP) level, and interleukin (IL) 4, IL-5, IL-10 values, and lung function were measured on admission and at discharge in each patient. Results: We observed significant decreases in the levels of MPO, EDN, CRP, and IL-4, with significant improvement in lung function after treatment. We then classified the subjects into two groups of different clinical phenotypes: eosinophilic asthma exacerbation (EAE) group and non-EAE group. EDN levels were higher and lung functions were lower in the EAE group. Also, we found that the EDN level was a significant biomarker useful for predicting the number of days for hospital stay. Conclusion: We found that EDN can act as a biomarker that reflects lung function, and that EDN could act as a prognostic biomarker, which demonstrated the complex role of EDN in children experiencing AE.

Changes in the Clinical Characteristics of Kawasaki Disease After Coronavirus Disease (COVID-19) Pandemic: A Database Analysis.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on Kawasaki disease (KD) has not yet been established. We investigated changes in the observed number and severity of KD cases and accompanying coronary artery complications during the COVID-19 pandemic in Korea. METHODS: This retrospective observational study included patients aged < 18 years with acute-phase KD diagnosed between March 2018 and February 2021. Data were extracted from the Clinical Data Warehouse that houses data from five affiliated university hospitals in Korea. We analyzed changes in the number of patient admissions and clinical characteristics, including cardiac complications, before and after the onset of the COVID-19 pandemic. RESULTS: A total of 475 admissions were included in the analysis. After March 2020, we observed a significant decrease of 33% in the number of hospitalizations for KD compared with the average number of hospitalizations during the previous 2 years. The number of admissions per month significantly decreased by 7.9 persons/month (95% confidence interval, -13.8 to -2.0; P < 0.05) compared with that before COVID-19. By contrast, the proportion of patients aged < 1 year with KD increased. The proportion of patients with refractory KD and the rate of cardiac complications did not change significantly. CONCLUSION: Since the onset of the COVID-19 pandemic, the total number of hospital admissions for KD has decreased in Korea. Although the proportion of admissions of infants aged < 1 year increased, no changes were observed in clinical courses and complications.

Level of interleukin-18 binding protein is significantly different in patients with anaphylaxis than urticaria.

BACKGROUND: Acute urticaria is a common cutaneous disease encountered in children, while anaphylaxis can show cutaneous symptoms as well as systemic symptoms. One study found that urticaria tends to precede anaphylaxis, but studies on the different role of eosinophils and related cytokines in anaphylaxis and urticaria are lacking. OBJECTIVE: The aim of this study was to compare the clinical features, total eosinophil count, serum levels of interleukin (IL)-18, IL-18 binding protein (BP), IL-1 receptor-like (RL) 1, and IL-33 and compare with tryptase to examine if any differences could be found between patients who experienced anaphylaxis and urticaria. METHODS: We included 63 patients with urticaria and 52 patients with anaphylaxis. We measured total eosinophil count and the serum levels of total IgE, tryptase, IL-18, IL-18BP, IL-1RL1, and IL-33, and we compared the differences between the groups. Lastly, receiver operating characteristic curves were constructed to determine which factors accurately diagnosed anaphylaxis. RESULTS: No significant differences were observed in the clinical characteristics or sensitization between urticaria group and anaphylaxis group. Laboratory findings showed that total eosinophil count and IL-18BP were significantly lower in the anaphylaxis group, compared with the urticaria group. IL-18BP showed significant correlation with tryptase. The receiver operating characteristic curve for IL-18BP for diagnosing anaphylaxis had an area under the curve of 0.530. CONCLUSIONS: IL-18BP level was significantly different in patients with anaphylaxis compared to those with urticaria. Serum IL-18BP level may be used to differentiate between the patients with urticaria or anaphylaxis.

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.

Efficacy of glucocorticoids for the treatment of macrolide refractory mycoplasma pneumonia in children: meta-analysis of randomized controlled trials.

BACKGROUND: Mycoplasma pneumoniae is one of the most common pathogens causing community acquired pneumonia in children. Although the rate of macrolide-refractory Mycoplasma pneumoniae (MRMP) has increased, systemic glucocorticoids as a treatment option has not been validated yet. The purpose of this study was to assess the efficacy of glucocorticoids add-on in the treatment of MRMP in children through systematic review and meta-analysis. METHODS: Data sources A systematic literature search was conducted using ten electronic bibliographic databases including English, Korean, Chinese and Japanese languages, up to March 8, 2018. Study selection The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and selected randomized control trials which compared the efficacy of glucocorticoids add-on to macrolide in the treatment of MRMP in children. Data extraction Two independent reviewers extracted: primary outcomes as hospital days, fever duration, and change in C-reactive protein (CRP) and main analysis was performed through meta-analysis with random effects model. RESULTS: Twenty-four unique randomized controlled trials met the inclusion criteria. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in conventional macrolide-treatment group (Weighted mean difference (WMD) = - 4.03 days). The mean length of fever duration was significantly shorter in the glucocorticoid treatment group in comparison with the conventional treatment group (WMD = -3.32 days). Level of CRP after treatment was significantly lower in the glucocorticoid treatment group than that in the conventional treatment group (WMD = -16.03). Sensitivity analysis and subgroup analysis showed no significant improvement in heterogeneity. As limitations of the study, most of the studies included were from a single country and we were unable to control for heterogeneity across interventions, lack of standardized measures, and different time points of assessments across studies. CONCLUSIONS: Glucocorticoid add-on treatment for MRMP can significantly shorten the duration of fever and hospital stay and decrease the level of CRP. These results should be confirmed by adequately powered studies in the future.

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.

Lipid profiles in adolescents with and without asthma: Korea National Health and nutrition examination survey data.

BACKGROUND: Metabolic syndrome and dyslipidemia contribute to the development of a pro-inflammatory state in asthma. However, studies investigating the association between asthma and dyslipidemia have reported conflicting results. This study aimed to uncover the relationship between asthma and lipid profiles in adolescents using a national health and nutrition survey. METHODS: This cross-sectional study analyzed the 2010-2012 Korea National Health and Nutrition Examination Survey data and included 2841 subjects aged 11-18 years with fasting blood sample data. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed. We compared asthma prevalence between high-risk and low-risk lipid groups. RESULTS: There were 123 adolescents with asthma and 2718 without asthma (controls). The TC/HDL-C ratio, LDL-C/HDL-C ratio, and non-HDL-C levels were significantly higher in the asthma group than in the non-asthma group (P < 0.05). The high-risk groups displayed significantly higher asthma prevalence with higher TC, TG, LDL-C, and non-HDL-C levels and TG/HDL-C ratio than the low-risk groups (P < 0.05). After adjusting for potential confounding factors, the high-risk groups were associated with asthma according to their higher TC levels (adjusted odds ratio, 1.69; 95% confidence interval, 1.012-2.822) and TG/HDL-C ratios (adjusted odds ratio, 1.665; 95% confidence interval, 1.006-2.756). CONCLUSIONS: Asthma prevalence was greater in adolescents with a high TC level and TG/HDL-C ratio. In addition to the standard lipid profile, elevated TG/HDL-C ratio can be used as a useful additional lipid measure to evaluate interactions between dyslipidemia and asthma.

Eosinophil-derived neurotoxin as a biomarker for disease severity and relapse in recalcitrant atopic dermatitis.

BACKGROUND: Eosinophils are encountered in many skin diseases, but the role of eosinophils in atopic dermatitis (AD) remains uncertain. OBJECTIVE: To examine the role of serum eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), and total IgE as a biomarker of disease severity and relapse in severe recalcitrant AD. METHODS: We enrolled 99 patients with AD: 37 with severe recalcitrant AD, 20 with severe AD, and 42 with mild to moderate AD. We examined the difference in serum level of total IgE, ECP, and EDN between the groups and whether any correlation existed between disease severity and ECP or EDN. Lastly, difference in levels of ECP or EDN between those who experienced relapse was examined in the severe recalcitrant group. RESULTS: Serum levels of total IgE, ECP, and EDN were significantly higher in the severe recalcitrant AD group and severe AD group compared with the mild to moderate AD group. No significant difference was found in serum levels of total IgE, ECP, and EDN between the severe recalcitrant group and severe group. EDN had a significant positive correlation with the SCORing Atopic Dermatitis. No significant correlation was found between EDN and ECP. In the severe recalcitrant group, 29.7% of patients experienced relapse, and EDN was significantly higher in those who experienced relapse. The cutoff value of EDN for predicting relapse was 64.5. CONCLUSION: EDN correlated with the disease severity of AD. EDN may predict relapse in severe recalcitrant AD. The EDN serum level could be considered a candidate molecule as a clinical biomarker for evaluating AD disease activity and a predictor of relapse.

Comparison of skin-sparing mastectomy using LigaSure™ Small Jaw and electrocautery.

BACKGROUND: Skin-sparing mastectomy (SSM) is increasingly used in patients with breast cancer. We compared the differences between use of electrocautery and LigaSure™ Small Jaw in patients with breast cancer who underwent SSM. METHODS: Between January 2012 and December 2015, 81 patients with breast cancer who underwent SSM were selected and were divided into the electrocautery group and the LigaSure™ Small Jaw group based on the devices that were used. Clinicopathological characteristics, body mass index, operative time, and weight of removed breast were obtained from medical records. Total amount and days of drain use, until removal, and postoperative skin necrosis, requiring debridement, were also analyzed. RESULTS: The study population consisted of 50 patients in the electrocautery group and 31 in the LigaSure™ Small Jaw group. The latter group has significantly shorter operative time (117.5 ± 16.9 vs. 104.0 ± 23.6 min, P = 0.004). The mean total volume of drainage was less (805 ± 278 vs. 694 ± 131 mL, P = 0.017) and mean duration of drainage was also significantly shorter in the LigaSure™ Small Jaw group (11.3 ± 2.5 vs. 10.1 ± 2.0 days, P = 0.029). CONCLUSIONS: The use of LigaSure™ Small Jaw during skin-sparing mastectomy shortened the operative time and duration of drainage and reduced the total volume of drainage.

Pre-ablation stimulated thyroglobulin is a better predictor of recurrence in pathological N1a papillary thyroid carcinoma than the lymph node ratio.

BACKGROUND: Papillary thyroid carcinomas (PTC) with lymph node metastases have a high recurrence rate. We analyzed the potential of lymph node ratio (LNR) and the level of pre-ablation stimulated thyroglobulin (sTg) as risk factors predicting recurrence in patients with pathological N1a PTC. MATERIALS AND METHODS: This study involved 192 patients with pathologically confirmed PTC and central neck lymph node metastases who underwent total thyroidectomy with central lymph node dissection (CLND). The clinico-pathological characteristics, the pre-ablation sTg level and post-treatment recurrences were examined. Univariate and multivariate analyses were performed to identify factors associated with recurrence in these patients. RESULTS: During a median follow-up of 63 months, 17 patients had loco-regional recurrences. Receiver operating characteristic curve analysis showed that the appropriate cut-off values for LNR and the pre-ablation sTg level was 0.48 and 9.3 ng/mL, respectively. Patients with LNR values of ≥0.48 had a significantly worse disease-free survival (DFS) than those with LNR values of <0.48 (P = 0.015), and patients with pre-ablation sTg level values of ≥9.3 ng/mL had significantly worse DFS than those with pre-ablation sTg level values <9.3 ng/mL (P < 0.001). Relative to patients with LNR values of <0.48, those with LNR values of ≥0.48 had higher median pre-ablation sTg level values (0.55 vs. 4.20; P < 0.001). The correlation covariant between the LNR value and the pre-ablation sTg level value was r = 0.454 (P < 0.001). Multivariate analysis showed that a LNR value of ≥0.48 (P = 0.386) was not an independent risk factor for recurrence. To the contrary, a pre-ablation sTg level value of ≥9.3 ng/mL (P < 0.001) was an independent risk factor for recurrence. CONCLUSION: A high pre-ablation sTg level is a better predictor of recurrence in pathological N1a PTC than a high LNR value. Careful follow-up of patients with this risk factor is recommended.

Effect of breastfeeding on lung function in asthmatic children.

Effect of breastfeeding on the protective effect on asthma has been studied extensively but remains controversial. Studies regarding the effect of breastfeeding on lung function have also been conflicting. The aim of this study was to determine the influence of breastfeeding on lung function in asthmatic children. We included 555 patients who visited Severance Children's Hospital Allergy Clinic with asthma. Pulmonary function, its bronchodilator response (BDR), fractional nitric oxide, and sputum eosinophils were measured. Parents completed questionnaires with information on feeding practices, family history of allergic disease, exposure to tobacco smoke, and presence of pets. Breastfeeding duration was categorized as not breastfed, breastfed <6 months, and breastfed ≥6 months. Within the asthma group, we stratified by atopic sensitization. We also investigated whether exclusivity of breastfeeding had any modifying effect on lung function. In the asthma group, ratio of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) significantly increased according to breastfeeding duration: 86.6 ± 8.7 for not breastfed group, 87.2 ± 8.6 for <6 months group, and 88.8 ± 7.7 for ≥6 months group. Within asthma group, only the nonatopic subjects showed a significant increase of FEV1/FVC, maximal midexpiratory flow, and decrease of maximal response to BD according to breastfeeding duration. Increase in FEV1/FVC was seen in the exclusive breastfeeding for ≥6 months group compared with those partially breastfed but FVC was significantly lower in those exclusively breastfed <6 months group compared with those partially breastfed. BDR decreased with breastfeeding duration in the nonatopic asthma group. In conclusion, longer duration of breastfeeding appears to have a favorable effect on lung function in asthmatic children, especially in nonatopic subjects.

Incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in South Korea.

INTRODUCTION: Children's rare lung diseases are a heterogeneous group of rare lung diseases with significant morbidity and mortality. There is very limited information on the incidence and prevalence of children's rare lung diseases in Asia. We investigated the nationwide incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in Korea. METHODS: We studied patients who were diagnosed with rare lung diseases coded per International Statistical Classification of Diseases and Related Health Problems, 10th Edition and registered in the national rare diseases database of confirmed patients. Data was extracted from the Korean National Health Insurance Service Claims database over 2019-2021. RESULTS: Average incidence rate was 12.9 new cases per million children per year, and average prevalence rate was 60.2 cases per million children during the study period of 2019-2021. We found that more than 65% of new cases were diagnosed before 2 years of age. ChILD, primary ciliary dyskinesia, and cystic fibrosis were usually diagnosed after 6 years of age. Congenital airway and lung anomalies were often diagnosed before 2 years of age. Busan and Gyeongsangnam-do residents tended to visit hospitals near their place of residence, while residents of other areas tended to visit hospitals in Seoul regardless of their area of residence. CONCLUSIONS: We examined the epidemiology of rare lung diseases in children in South Korea. Our estimation of the incidence and prevalence could be used for sustainable health care and equitable distribution of health care resources.

Establishment and long-term expansion of adult hepatobiliary organoids co-cultured with liver endothelial cells.

The liver has a unique ability to regenerate in response to injury or disease with hepatocytes and biliary epithelial cells (BECs) driving the regenerative response. Liver progenitor cells (LPCs) also play role in regeneration with the ability to differentiate into either hepatocytes or BECs. However, during chronic liver disease, the regenerative capacity of the liver is impaired. The use of LPCs is a promising therapeutic strategy for patients with chronic liver diseases. LPCs can be expanded in vitro as self-renewing organoids, however, most approaches to LPC organoids do not include critical cells from the LPC niche in 3D organoid cultures. In this study, we highlight the role of liver endothelial cells (LiECs), as a part of LPC niche, in supporting the hepatobiliary organoids in long-term culture even in the absence of defined growth supplements, such as Wnt agonists. Furthermore, LiECs alter the gene expression profile of hepatobiliary organoids involved in inflammation, migration, extracellular matrix organization, and receptor signaling pathway through paracrine manner. Our findings expand the role of LiECs for regulating stemness of LPCs and elucidate a role for niche cells in a LPC organoid co-culture model with a reduction in growth supplements.

Evidence-based management guidelines for noncystic fibrosis bronchiectasis in children and adolescents.

Noncystic fibrosis bronchiectasis is a chronic respiratory disease that carries high socioeconomic and medical burdens and is caused by diverse respiratory illnesses. To improve clinical outcomes, early recognition, active treatment of exacerbations, and prevention of further exacerbations are essential. However, evidence for the treatment and prevention of acute exacerbation of noncystic fibrosis bronchiectasis, especially in children, is lacking. Therefore, the evidence- and consensus-based guidelines for medical and nonmedical treatment strategies for noncystic fibrosis bronchiectasis in children and adolescents were developed by the Korean Academy of Pediatric Allergy and Respiratory Disease using the methods recommended by the Grading of Recommendations Assessment, Development, and Evaluation working group with evidence published through July 2, 2020. This guideline encompasses evidence-based treatment recommendations as well as expert opinions, addressing crucial aspects of the treatment and management of non-cystic fibrosis bronchiectasis in children. This includes considerations for antibiotics and airway clearance strategies, particularly in areas where evidence may be limited. Large, well-designed, and controlled studies are required to accumulate further evidence of management strategies for noncystic fibrosis bronchiectasis in children and adolescents.