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.

Clinical Manifestations and Genotype of Primary Ciliary Dyskinesia Diagnosed in Korea: Multicenter Study.

PURPOSE: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder that leads to secondary ciliary dysfunction. PCD is a rare disease, and data on it are limited in Korea. This study systematically evaluated the clinical symptoms, diagnostic characteristics, and treatment modalities of pediatric PCD in Korea. METHODS: This Korean nationwide, multicenter study, conducted between January 2000 and August 2022, reviewed the medical records of pediatric patients diagnosed with PCD. Prospective studies have been added to determine whether additional genetic testing is warranted in some patients. RESULTS: Overall, 41 patients were diagnosed with PCD in 15 medical institutions. The mean age at diagnosis was 11.8 ± 5.4 years (range: 0.5 months-18.9 years). Most patients (40/41) were born full term, 15 (36.6%) had neonatal respiratory symptoms, and 12 (29.3%) had a history of admission to the neonatal intensive care unit. The most common complaint (58.5%) was chronic nasal symptoms. Thirty-three patients were diagnosed with transmission electron microscopy (TEM) and 12 patients by genetic studies. TEM mostly identified outer dynein arm defects (alone or combined with inner dynein arm defects, n = 17). The genes with the highest mutation rates were DNAH5 (3 cases) and DNAAF1 (3 cases). Rare genotypes (RPGR, HYDIN, NME5) were found as well. Chest computed tomography revealed bronchiectasis in 33 out of 41 patients. Among them, 15 patients had a PrImary CiliAry DyskinesiA Rule score of over 5 points. CONCLUSIONS: To our knowledge, this is the first multicenter study to report the clinical characteristics, diagnostic methods, and genotypes of PCD in Korea. These results can be used as basic data for further PCD research.

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.

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.

Multicenter Surveillance of Cystic Fibrosis in Korean Children.

PURPOSE: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is rare among non-Caucasians. We aimed to identify the clinical features and CFTR mutations in Korean children. METHODS: We included 18 pediatric patients with CF diagnosed using sweat chloride test or genetic analysis for 30 years. HEK293 cells were transfected with wild-type CFTR, ΔF508-CFTR, and L441P-CFTR mutant plasmids for 24 hours and treated with CFTR correctors (VX809 and VX661). RESULTS: The median age at diagnosis was 9.2 years. Eleven patients had growth retardation, and 6 had a respiratory failure at diagnosis. Genetic analysis was used for all patients, while sweat testing was for 8 patients. At diagnosis, the median z scores of forced expiratory volume in one second (FEV1), FEV1/forced vital capacity, and forced expiratory flow at 25%-75% of forced vital capacity were -3.61 (-5.78, 1.78), -3.38 (-4.40, -0.60), and -4.45 (-5.78, 0.54), respectively. Two patients were treated with dornase alfa and only one with CFTR modulator. Patients were followed up for 3.7 years as a median. Four patients died at 10.6 years, with 4.2 years of post-diagnosis survival. The most common mutation was exon 16-17b deletion (19.4%). Among 11 single nucleotide variants, c.1322T>C (p.Leu441Pro, L441P) was detected in 4 patients. In the functional assay, L441P-CFTR correction was well restored by CFTR correctors compared with ΔF508. CONCLUSIONS: CF is extremely rare in Korean children and is caused by different mutations from those commonly observed in Caucasians. Early diagnosis and treatment availability may improve outcomes. CFTR modulators may be effective for Asian patients with rare CFTR mutations, c.1322T>C (p.Leu441Pro).

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.

Clinical Characteristics of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Korean Children: A Multicenter Retrospective Study.

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

Pulmonary function of healthy Korean children from three independent birth cohorts: Validation of the Global Lung Function Initiative 2012 equation.

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), normal (≥-2 and ≤2), and high (>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.

Association between sensitization and allergic diseases in 7-years-old Korean children.

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. CONCLUSIONS: 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.

Heterogeneity of Childhood Asthma in Korea: Cluster Analysis of the Korean Childhood Asthma Study Cohort.

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.

Vegetable dietary pattern may protect mild and persistent allergic rhinitis phenotype depending on genetic risk in school children.

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.

Asthma predictive index as a useful diagnostic tool in preschool children: a cross-sectional study in Korea.

BACKGROUND: It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children. PURPOSE: This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children. METHODS: We performed a population-based cross-sectional study in 916 preschool children aged 4-6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma. RESULTS: The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed. CONCLUSION: The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.

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.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification.

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.

Associated Factors for Asthma Severity in Korean Children: A Korean Childhood Asthma Study.

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.

Clinical characteristics and etiologies of bronchiectasis in Korean children: A multicenter retrospective study.

BACKGROUND: Bronchiectasis is a chronic pulmonary disease characterized by progressive and irreversible bronchial dilatation. The aim of the present study was to investigate the etiologies and clinical features of bronchiectasis in Korean children. METHODS: We performed a retrospective review of the medical records for children diagnosed with bronchiectasis between 2000 and 2017 at 28 secondary or tertiary hospitals in South Korea. RESULTS: A total of 387 cases were enrolled. The mean age at diagnosis was 9.2 ±â€¯5.1 years and 53.5% of the patients were boys. The most common underlying cause of bronchiectasis was preexisting respiratory infection (55.3%), post-infectious bronchiolitis obliterans (14.3%), pulmonary tuberculosis (12.3%), and heart diseases (5.6%). Common initial presenting symptoms included chronic cough (68.0%), recurrent pneumonia (36.4%), fever (31.1%), and dyspnea (19.7%). The most predominantly involved lesions were left lower lobe (53.9%), right lower lobe (47.1%) and right middle lobe (40.2%). No significant difference was observed in the distribution of these involved lesions by etiology. The forced expiratory volume in 1 s (FEV1) levels were lowest in cases with interstitial lung disease-associated bronchiectasis, followed by those with recurrent aspiration and primary immunodeficiency. CONCLUSIONS: Bronchiectasis should be strongly considered in children with chronic cough and recurrent pneumonia. Long-term follow-up studies on pediatric bronchiectasis are needed to further clarify the prognosis and reduce the disease burden in these patients.

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.

Profiles and characteristics of bronchial responsiveness in general 7-year-old children.

BACKGROUND: 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. METHODS: 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 of <4 mg/mL) and group 2 (PC20 of ≥4 mg/mL and <16 mg/mL), and nonresponsive BRs were categorized into group 3 (final FEV1 percentage fall after inhaling 16 mg/mL of methacholine [FEV1%fall] of >15% and ≤20%), group 4 (FEV1%fall of >10% and ≤15%), and group 5 (FEV1%fall of ≤10%). RESULTS: 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.

Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children.

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.