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.

Clinicopathological significance and the associated signaling pathway of p21-activated kinase 1 (PAK1) in colorectal cancer.

The aim of this study was to evaluate the clinicopathological significance and associated signaling pathways of p21-activated kinase 1 (PAK1) in colorectal cancer (CRC). PAK1 immunohistochemical expression was investigated in 246 human CRC tissues to evaluate its clinicopathological significance and prognostic role. Correlations between PAK1 and the immunoscore, HIF-1α, and pFOXO1 were also evaluated. PAK1 was expressed in 169 of 246 CRC tissues (68.7%). PAK1 expression significantly correlated with the metastatic lymph node ratio (P = 0.023). However, PAK1 expression did not correlate with tumor size, tumor location, tumor differentiation, lymphovascular and perineural invasion, or distant metastasis. PAK1 expression was significantly higher in CRC with a low immunoscore than in CRC with a high immunoscore (P = 0.017). In addition, there were significant correlations between PAK1, HIF-1α, and pFOXO1 expression (P = 0.001 and P = 0.024, respectively). Patients with PAK1 expression had worse overall and recurrence-free survival than those without PAK1 expression (P 0.001 and P = 0.001, respectively). PAK1 expression was significantly correlated with worse prognosis in CRCs patients. In addition, PAK1 expression was significantly correlated with a low immunoscore and high expression of HIF-1α and pFOXO1 in CRCs.

Diagnostic Accuracy of ki-67 Labeling Index in Endoscopic Ultrasonography-Fine-Needle Aspiration Cytology and Biopsy of Pancreatic Neuroendocrine Neoplasms.

BACKGROUND: This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). METHODS: Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. RESULTS: The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713-0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681-0.794) and 0.839 (95% CI, 0.738-0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590-0.917) and 0.998 (95% CI, 0.987-1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145-489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. CONCLUSIONS: Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.

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.

Navigation Guided Biopsy Is as Effective as Frame-Based Stereotactic Biopsy.

BACKGROUND: Stereotactic biopsy is a standard procedure for brain biopsy. However, with advances in technology, navigation-guided brain biopsy has become a well-established alternative. Previous studies have shown that frameless stereotactic brain biopsy is as effective and safe as frame-based stereotactic brain biopsy is. In this study, the authors evaluate the diagnostic yield and complication rate of frameless intracranial biopsy. MATERIALS AND METHODS: We reviewed data from biopsy performed patients between March 2014 and April 2022. We retrospectively reviewed medical records, including imaging studies. Various intracerebral lesions were biopsied. Diagnostic yield and post-operative complications were compared with those of frame-based stereotactic biopsy. RESULTS: Forty-two frameless navigation-guided biopsy were performed, and the most common pathology was primary central nervous system lymphoma (35.7%), followed by glioblastoma (33.3%), and anaplastic astrocytomas (16.7%), respectively. The diagnostic yield was 100%. Post-operative intracerebral hematoma occurred in 2.4% of cases, but it was not symptomatic. Thirty patients underwent frame-based stereotactic biopsy, and the diagnostic yield was 96.7%. There was no difference in diagnostic rates between two methods (Fisher's exact test, p = 0.916). CONCLUSIONS: Frameless navigation-guided biopsy is as effective as frame-based stereotactic biopsy is, without causing further complications. We consider that frame-based stereotactic biopsy is no longer needed if frameless navigation-guided biopsy is used. A further study will be needed to generalize our results.

Epidemiology of patients with asthma in Korea: Analysis of the NHISS database 2006-2015.

Background: There has been a concerning increase in the prevalence and socioeconomic burden of asthma in Korea. Korea's National Health Insurance System (NHIS) covers insurance payment and claims management for all Koreans. Using National Health Insurance Sharing Service (NHISS) claims data. This study aimed to investigate patterns of healthcare utilization and direct cost in patients with asthma over a 10-year period. Methods: In this retrospective population-based study, we examined NHISS claims records between July 2005 and June 2016 and investigated healthcare utilization among patients with asthma based on age group and severity of disease (non-severe asthma [NSA] and severe asthma [SA]). Results: From 2006 to 2015, the total number of patients with asthma in Korea steadily increased from 743 968 to 2 286 309, with a corresponding increase in prevalence from 1.62% to 4.74%. The proportion of patients with SA decreased from 3.16% in 2006 to 1.56% in 2015; the proportion was consistently higher in men than in women. In addition, patients with SA had a higher cost per outpatient visit than patients with NSA, and the number of outpatient visits per year increased. The inhaled corticosteroid (ICS) prescription rate among patients with asthma decreased from 22.9% in 2006 to 15.7% in 2015. Furthermore, for a period of 10 years, more than 40% of patients with SA have been prescribed short-acting ß-2 agonists (SABAs). Conclusions: Although patients with SA comprised a small proportion of patients with asthma, they incurred greater medical costs per person. The pharmaceutical prescription pattern indicated a lack of ICS-based prescriptions and frequent SABA prescriptions.

The chronological changes in the seroprevalence of anti-hepatitis A virus IgG from 2005 to 2019: Experience at four centers in the capital area of South Korea.

Although universal vaccination has been administered to toddlers, South Korea has had periodic nationwide outbreaks of acute hepatitis A since the late 2000s. We examined the chronological changes in the seroprevalence of anti-hepatitis A virus (HAV) immunoglobulin G (IgG) over the past 15 years (2005-2019). We retrospectively collected data from 45,632 subjects who underwent anti-HAV IgG testing without evidence of acute HAV infection at four centers in the capital area of South Korea between January 2005 and December 2019. The seroprevalence of anti-HAV IgG was analyzed according to age and compared among seven age groups and five time periods. Additionally, age-period-cohort analyses were used to identify the age, period, and cohort effects of the seroprevalence of anti-HAV IgG. The mean age of the enrolled subjects was 39.2 ±â€…19.2 years, and the average anti-HAV IgG positivity rate was 66.4%. During the 15 years, the seroprevalence of anti-HAV IgG in people aged 0 to 19 years significantly increased over time (P < .001). In people aged 20 to 29 years, the seroprevalence slightly decreased to that of the early 2010s (31.3% in 2005-2007 to 19.7% in 2011-2013) but rebounded to 39.5% in 2017 to 2019. In contrast, the seroprevalence of anti-HAV IgG in those aged 30 to 49 years decreased over time (P < .001). The seroprevalence of anti-HAV IgG in those aged 20 to 39 years in 2017 to 2019 was still less than 40%. In addition, the seroprevalence of anti-HAV IgG in people aged 50 to 59 years has recently decreased. Since the introduction of the universal vaccination, the seroprevalence of anti-HAV IgG in children and young adults has gradually increased. However, the seroprevalence of anti-HAV IgG in people in their 20s remains low, and the seroprevalence of anti-HAV IgG in people in their 30s and 40s is gradually decreasing. Therefore, a new strategy for HAV vaccination is needed for those in their 20s to 40s.

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.

Changing Features of Liver Injury in COVID-19 Patients: Impact of Infection with the SARS-CoV-2 Delta (B.1.617.2) Variants.

BACKGROUND: There is growing evidence that abnormal liver function tests (LFTs) are common in patients with coronavirus disease 2019 (COVID-19). However, it is not known whether viral involvement in the liver differs according to the strain. We investigated the impact on liver injury in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) variants. MATERIALS AND METHODS: We conducted a single-center, retrospective cohort study, including 372 patients admitted during the pre-Delta period (PDP: between February 1 and November 30, 2020) and 137 patients admitted during the Delta period (DP: between August 1 and August 31, 2021). Initial liver injury was defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 × the upper limit of normal (ULN) or alkaline phosphatase (ALP) or total bilirubin ≥2 × the ULN within 3 days from admission. RESULTS: Of 509 patients with COVID-19 included in our study, 38 (7.5%) patients had initial liver injury. The DP group had a significantly higher rate of initial liver injury than the PDP group (PDP: 5.9% vs. DP: 11.7%, P = 0.028). The DP group (adjusted odds ratio [aOR]: 2.737, 95% confidence interval [CI]: 1.322 - 5.666) was independently associated with initial liver injury. During hospitalization, 160 (31.4%) patients had severe COVID-19. The DP group and initial liver injury had higher odds of progressing to severe COVID-19 (aOR: 2.664, 95% CI: 1.526 - 4.648, and aOR: 4.409, 95% CI: 1.816 - 10.707, respectively). The mediation analysis suggested that initial liver injury mediates the relationship between SARS-CoV-2 Delta variant infection and severe COVID-19 (unstandardized beta coefficient = 0.980, Standard error = 0.284, P = 0.001). CONCLUSION: Initial liver injury is more common in COVID-19 patients with Delta variants. Also, Delta variants and initial liver injury are associated with poor clinical outcomes.

Clinical Characteristics and Treatment Outcomes of Patients with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection: Experience at a Single Center in Korea.

BACKGROUND: Because of the very low incidence of human immunodeficiency virus (HIV) coinfection in Korea, data on hepatitis C virus (HCV)/HIV coinfection are limited. This study aimed to investigate the clinical characteristics and treatment outcomes of patients with HCV/HIV coinfection in Korea. METHODS: We performed a retrospective cohort study of all HCV-monoinfected and HCV/HIV-coinfected patients treated with antivirals at National Medical Center in Seoul, Korea, between January 2009 and March 2020. RESULTS: We enrolled 220 HCV-monoinfected and 23 HCV/HIV-coinfected patients treated with antivirals. The HCV/HIV-coinfected patients were younger (HCV vs. HCV/HIV: 57.3 ± 11.3 vs. 40.7 ± 10.1 years, P < 0.001) and had a higher proportion of men (HCV vs. HCV/HIV: 54.5% [n = 120] vs. 91.3% [n = 21], P < 0.001) than the HCV-monoinfected patients. Genotype 1b and 2 were most common in both HCV monoinfection and HCV/HIV coinfection groups. HCV-monoinfected patients had a higher incidence of genotype 1b and 2 than HCV/HIV-coinfected patients (HCV vs. HCV/HIV: 95.4% [n = 210] vs. 73.9% [n = 17], P < 0.001), while the HCV/HIV-coinfected patients had genotype 1a (HCV vs. HCV/HIV: 1.8% [n = 4] vs. 21.7% [n = 5], P < 0.001). The fibrosis-4 index was significantly lower in the HCV/HIV-coinfected patients than in the HCV-monoinfected patients (HCV vs. HCV/HIV: 3.81 ± 3.38 vs. 1.66 ± 1.10, P < 0.001). Among the direct-acting antivirals (DAA)-treated patients, the sustained viral response (SVR) rate did not differ significantly between both groups (HCV vs. HCV/HIV: 94.9% [93/99] vs. 90.9% [10/11], P = 0.480). CONCLUSION: In Korea, the HCV/HIV-coinfected patients who received antiviral treatment were younger, had higher proportion of men and incidence of genotype 1a, and had less advanced fibrosis than the HCV-monoinfected patients. In actual clinical settings, HCV/HIV-coinfected patients show excellent SVR to DAA treatment, similar to HCV-monoinfected patients.

Current Asthma Prevalence Using Methacholine Challenge Test in Korean Children from 2010 to 2014.

BACKGROUND: Most epidemiological studies depend on the subjects' response to asthma symptom questionnaires. Questionnaire-based study for childhood asthma prevalence may overestimate the true prevalence. The aim of this study was to investigate the prevalence of "Current asthma" using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and methacholine challenge test in Korean children. METHODS: Our survey on allergic disease included 4,791 children (age 7-12 years) from 2010 to 2014 in Korean elementary schools. Bronchial hyperresponsiveness (BHR) was defined as provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) ≤ 16 mg/mL. "Current asthma symptoms" was defined as positive response to "Wheezing, current," "Treatment, current," or "Exercise, current." "Current asthma" was defined when the subjects with "Current asthma symptoms" showed BHR on the methacholine challenge test or had less than 70% of predicted FEV1 value. RESULTS: The prevalence of "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," "Exercise, current," and "Current asthma symptoms" was 19.6%, 6.9%, 10.0%, 3.3%, 3.5%, and 9.6%, respectively, in our cross-sectional study of Korean elementary school students. The prevalence of BHR in elementary school students was 14.5%. The prevalence of BHR in children with "Wheezing, ever," "Wheezing, current," "Diagnosis, ever," "Treatment, current," and "Exercise, current" was 22.3%, 30.5%, 22.4%, 28.8%, and 29.9%, respectively. BHR was 26.1% in those with "Current asthma symptoms." The prevalence of "Current asthma" was 2.7%. CONCLUSIONS: Our large-scale study provides 2.7% prevalence of current asthma in Korean elementary school children. Since approximately one third of the children who have "Current asthma symptoms" present BHR, both subjective and objective methods are required to accurately predict asthma in subjects with asthma symptoms.

Diagnostic Performance of Serum Asialo α1-Acid Glycoprotein Levels to Predict Liver Cirrhosis.

Background/Aims: To date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of serum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result. Methods: We conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrhosis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups. Results: Serum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 µg/mL vs 1.42 µg/mL, p<0.001). Additionally, when comparing patients in each cirrhotic group (Child-Pugh grades A, B, and C) to those with chronic hepatitis, AsAGP levels were significantly higher in all the cirrhotic groups (p<0.05, p<0.01, p<0.001, respectively). The sensitivity and specificity of AsAGP for detecting cirrhosis were 79.2% and 64.6%, respectively, and the area under the curve value was 0.733. The best diagnostic cutoff to predict cirrhosis was 1.4 µg/mL. AsAGP and bilirubin were found to be independent risk factors for the prediction of cirrhosis in the logistic regression analysis. Conclusions: Serum AsAGP showed an acceptable diagnostic performance in predicting liver cirrhosis.

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.

Bacterial Microbiota-derived Extracellular Vesicles in Children With Allergic Airway Diseases: Compositional and Functional Features.

PURPOSE: Bacterial extracellular vesicles (EVs) play crucial roles in bacteria-host interactions. Due to their cargo, EVs are considered fingerprints of the parent cell, which are detectable in body fluids. We studied the composition and function of bacterial microbiota-derived EVs genes in urine to evaluate whether they have specific characteristics concerning allergic airway disease. METHODS: Subjects were from elementary school surveys and classified into 3 groups according to questionnaires and sensitization to aeroallergens: the allergic airway group (AA, n = 16), atopic controls (AC, n = 7) and healthy controls (HC, n = 26). The bacterial EVs were isolated from voided urine samples, their nucleic acid was extracted for 16S ribosomal RNA pyrosequencing and then characterized using α-diversity, ß-diversity, network analysis, intergroup comparison of bacterial composition and predicted functions, and correlation with total immunoglobulin E (IgE), eosinophils% and fractional exhaled NO. RESULTS: The compositional α-diversity was the highest in AA, while functional α-diversity was the highest in HC. AA had a distinct clustering with the least intersample variation. Klebsiella, Haemophilus, members from Lachnospiraceae and Ruminococcaceae, and the pathways of sphingolipid and glycerolipid metabolism, and biosynthesis of peptidoglycan and lysine were the highest in AA and positively correlated with total IgE or eosinophil%. Genetic information processing function contributed to 48% of the intergroup variance and was the highest in AA. Diaphorobacter, Acinetobacter, and the pathways of short-chain fatty acids and anti-oxidants metabolism, lysine and xenobiotic degradation, and lipopolysaccharide biosynthesis were the lowest in AA and negatively correlated with total IgE or eosinophil%. The bacterial composition and function in AC were closer to those in HC. The bacterial network was remarkably dense in HC. CONCLUSIONS: The bacterial microbiota-derived EVs in urine possess characteristic features in allergic airway disease with a remarkable correlation with total IgE and eosinophil%. These findings suggest that they may play important roles in allergic airway diseases.

Urine Microbe-Derived Extracellular Vesicles in Children With Asthma.

PURPOSE: Several studies have found significant associations between asthma and microbiome. However, it is challenging to obtain-sputum and bronchoalveolar lavage samples from pediatric patients. Thus, we used voided urine to show that urine microbe-derived extracellular vesicles (EVs) in asthma are an available source for clinical research. METHODS: Five urine samples were obtained at 2-3-month intervals from each patient with asthma (n = 20), and a single voided urine sample were obtained from each healthy child (n = 20). After isolating EVs, 16S rDNA pyrosequencing was performed. The Chao1 index and principal coordinate analysis (PCoA) were used to assess diversity. To predict microbiota functional capacities, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was used based on the Kyoto Encyclopedia of Genes and Genomes pathway database. Eight covariates were included in the EnvFit analysis to identify significant factors in the asthma group. RESULTS: The asthma group showed lower Chao1 bacterial richness, and PCoA-based clustering differed significantly. Two phyla, and 13 families and genera were enriched or depleted. Functional profiling revealed significant differences between the asthma and control groups. EnvFit analysis of correlation to age, sex, body mass index, infection, season, asthma phenotype, severity, and symptoms was not significant except for infections associated with visit 1 and the season of visit 2. CONCLUSIONS: This study showed that microbe-derived EVs were constantly altered in the urine of children with asthma, consistent with the findings of previous studies indicating microbiome changes in the lung and gut. The urine may reflect the specific pattern of microbiome EVs in children with asthma.

Association between Peak Expiratory Flow Rate and Exposure Level to Indoor PM2.5 in Asthmatic Children, Using Data from the Escort Intervention Study.

Various studies have indicated that particulate matter <2.5 µm (PM2.5) could cause adverse health effects on pulmonary functions in susceptible groups, especially asthmatic children. Although the impact of ambient PM2.5 on children's lower respiratory health has been well-established, information regarding the associations between indoor PM2.5 levels and respiratory symptoms in asthmatic children is relatively limited. This randomized, crossover intervention study was conducted among 26 asthmatic children's homes located in Incheon metropolitan city, Korea. We aimed to evaluate the effects of indoor PM2.5 on children's peak expiratory flow rate (PEFR), with a daily intervention of air purifiers with filter on, compared with those groups with filter off. Children aged between 6-12 years diagnosed with asthma were enrolled and randomly allocated into two groups. During a crossover intervention period of seven weeks, we observed that, in the filter-on group, indoor PM2.5 levels significantly decreased by up to 43%. (p < 0.001). We also found that the daily or weekly unit (1 µg/m3) increase in indoor PM2.5 levels could significantly decrease PEFR by 0.2% (95% confidence interval (CI) = 0.1 to 0.5) or PEFR by 1.2% (95% CI = 0.1 to 2.7) in asthmatic children, respectively. The use of in-home air filtration could be considered as an intervention strategy for indoor air quality control in asthmatic children's homes.

Normal Predicted Reference Values for Spirometry in Korean Children and Adolescents.

Pulmonary function tests are useful to evaluate airway obstructions and bronchial responsiveness. We aimed to determine the reference values applicable to Korean children and adolescents. In total, 5590 (2607 males, 2983 females) healthy children aged 4 to 17 years old were recruited from three regions in Korea. Simple and multiple regression analyses were applied using age, height, and weight as variables to predict the forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum mid-expiratory flow (MMEF) and the peak expiratory flow rate (PEFR). There were significant correlations between the variables and parameters (P < 0.001). The coefficient of determination (R2) values of polynomial equations with two variables were lower than those with two variables but higher than those of monomial equations based on height. The prediction equations by height were obtained, and the R2 value of the FEV1 was the highest. The predicted spirometric values for males were higher than those for females except for the MMEF. The R2 values for the FEV1 and FVC were higher than previous studies except for the R2 value of the FVC for males in European data. This study provided updated regression equations of normal predicted values for spirometry applicable to Korean children and adolescents.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 2. Management of H1-Antihistamine-Refractory Chronic Urticaria.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H1-antihistamines, even though the dose of H1-antihistamines is increased up to 4-fold. CSU that is not controlled with H1-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H1-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.