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.
Allergens ; Analgesics ; Animals ; Antipyretics ; Asian Continental Ancestry Group ; Asthma ; Bronchial Hyperreactivity ; Cats ; Child ; Classification ; Cohort Studies ; Comorbidity ; Dermatophagoides pteronyssinus ; Disease Management ; Humans ; Methacholine Chloride ; Odds Ratio ; Ownership ; Parturition ; Phenotype ; Prevalence ; Rhinitis, Allergic ; Risk Factors ; Skin

Abscess ; Adolescent ; Body Mass Index ; Child ; Classification ; Colonic Diseases ; Crohn Disease ; Diagnosis ; Europe ; Fistula ; Humans ; Inflammatory Bowel Diseases ; Korea ; Male ; Pediatrics ; Phenotype ; Retrospective Studies

0.2 and p<0.05. NOTCH1 was identified as a candidate network hub gene in cases. NOTCH1 transcripts significantly increased in lung tissues from HDLI cases compared to unexposed controls (p=0.05). NOTCH1 may play an important role in pulmonary fibrosis of HDLI.]]>
Child ; DNA Methylation ; Gene Expression Profiling ; Humans ; Humidifiers ; Korea ; Lung Injury ; Lung ; Methylation ; Pulmonary Fibrosis

Asthma ; Bronchitis ; Cohort Studies ; Cough ; Diagnosis ; Disease Management ; Eosinophils ; Epidemiology ; Female ; Gastroesophageal Reflux ; Humans ; Korea ; Lung Diseases ; Multivariate Analysis ; Observational Study ; Pregnant Women ; Retrospective Studies ; Tuberculosis

PURPOSE: The roles of gut microbiota on the natural course of atopic dermatitis (AD) are not yet fully understood. We investigated whether the composition and function of gut microbiota and short-chain fatty acids (SCFAs) at 6 months of age could affect the natural course of AD up to 24 months in early childhood.METHODS: Fecal samples from 132 infants were analyzed using pyrosequencing, including 84 healthy controls, 22 transient AD and 26 persistent AD subjects from the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort. The functional profile of the gut microbiome was analyzed by whole-metagenome sequencing. SCFAs were measured using gas chromatography-mass spectrometry.RESULTS: Low levels of Streptococcus and high amounts of Akkermansia were evident in transient AD cases, and low Clostridium, Akkermansia and high Streptococcus were found in children with persistent AD. The relative abundance of Streptococcus positively correlated with scoring of AD (SCORAD) score, whereas that of Clostridium negatively correlated with SCORAD score. The persistent AD group showed decreased gut microbial functional genes related to oxidative phosphorylation compared with healthy controls. Butyrate and valerate levels were lower in transient AD infants compared with healthy and persistent AD infants.CONCLUSIONS: Compositions, functions and metabolites of the early gut microbiome are related to natural courses of AD in infants.
Asthma ; Butyrates ; Child ; Clostridium ; Cohort Studies ; Dermatitis, Atopic ; Fatty Acids, Volatile ; Gas Chromatography-Mass Spectrometry ; Gastrointestinal Microbiome ; Humans ; Infant ; Metabolomics ; Metagenome ; Oxidative Phosphorylation ; Parturition ; Streptococcus

PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.
Agammaglobulinemia ; Diagnosis ; Exome ; Flow Cytometry ; Genetic Testing ; Granulomatous Disease, Chronic ; Humans ; Immunophenotyping ; Korea ; Leukocytes ; Lymphocyte Subsets ; Lymphohistiocytosis, Hemophagocytic ; Phenotype ; Retrospective Studies ; Seoul ; Severe Combined Immunodeficiency ; Tertiary Healthcare

BACKGROUND/AIMS: School nurses’ knowledge of inflammatory bowel disease (IBD) has not been evaluated. We aimed to investigate school nurses’ knowledge of IBD and determine whether education could improve this knowledge. METHODS: School nurses were invited to complete self-reported questionnaires on IBD. Then, IBD specialists from tertiary referral hospitals provided a 60-minute lecture with educational brochures on two occasions, with a 3-month interval. Within 6 months after the educational interventions, school nurses were asked to complete the same IBD questionnaire via e-mail. RESULTS: Among 101 school nurses who were invited to participate, 54 nurses (53.5%) who completed two consecutive questionnaires were included in this study (median age, 45 years; range, 25 to 59 years; 100% female); 11.1% and 7.4% of the study participants had no knowledge regarding ulcerative colitis and Crohn’s disease, respectively. They had heard of IBD most frequently from doctors (33.3%), followed by internet sources (25.9%). After 6 months, the number of nurses who could explain IBD to students with over 30% confidence increased from 24 (44.5%) to 42 (77.8%) (p < 0.001). Most nurses (81.5%) reported that the educational intervention was helpful for managing students with abdominal pain or diarrhea. The number of students who received IBD-related welfare services from the Daegu Metropolitan Office of Education doubled when compared with the corresponding number during the prior educational year. CONCLUSIONS: There is room for improvement in school nurses’ knowledge of IBD. A systematic educational program on IBD should be implemented for these nurses.
Abdominal Pain ; Colitis, Ulcerative ; Crohn Disease ; Daegu ; Diarrhea ; Education* ; Electronic Mail ; Humans ; Inflammatory Bowel Diseases* ; Internet ; Pamphlets ; Schools, Nursing ; Specialization ; Tertiary Care Centers

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic

PURPOSE: Testosterone replacement therapy is an effective treatment for late-onset hypogonadism (LOH) despite a few contraindications and side-effects. The aim of this study was to determine whether modified Ojayeonjonghwan (KH-204, Korean herbal formula) improved LOH. KH-204 is a strong antioxidant herbal formula. We evaluated the effect of Korean herbal prescription on androgen receptor (AR) expression in an aged rat model of LOH. MATERIALS AND METHODS: Eighteen-month-old rats were used as aged LOH rat models. Eighteen Sprague-Dawley rats were randomly divided into three equal groups of six animals each and treated with one of the following: 1) normal control group (oral administration with distilled water, n=6), 2) KH-204 200 group (oral administration with 200 mg/kg of KH-204, n=6), and 3) KH-204 400 group (oral administration with 400 mg/kg of KH-204, n=6). After four weeks of treatment (once daily, distilled water or KH-204), serum testosterone levels, changes in testicular and epididymal weight, Western blotting analysis of AR expression and measurement of oxidative stress were examined. RESULTS: Treatment with the herbal formulation KH-204 200 mg/kg and 400 mg/kg (1) increased the weights of testis and epididymis; (2) increased the level of serum testosterone; (3) increased the level of superoxide dismutase and reduced the level of 8-hydroxy-20-deoxyguanosine; and (4) upregulated AR expression in testicular tissue. CONCLUSIONS: KH-204 might be an effective alternative for LOH. It improves antioxidant mechanisms and increases testicular AR expression without side-effects.
Aging* ; Animals ; Blotting, Western ; Epididymis ; Hypogonadism* ; Male ; Models, Animal* ; Oxidative Stress ; Phytotherapy ; Prescriptions ; Rats* ; Rats, Sprague-Dawley ; Receptors, Androgen* ; Superoxide Dismutase ; Testis ; Testosterone ; Water ; Weights and Measures

PURPOSE: We report the outcomes of two- or three-muscle surgery on patients with large-angle exotropia exceeding 45 prism diopters (PDs). METHODS: We retrospectively analyzed data on 45 exotropia patients (> 45 PDs) who underwent two- or three-muscle surgery. We excluded patients with paralytic or restrictive strabismus, A- or V-pattern strabismus, a coexistent oblique dysfunction or nystagmus, and/or a history of prior extraocular muscle surgery. Only patients for whom at least 6 months of follow-up data were available were included. Successful surgery was defined as postoperative esotropia ≤ 5 PD, orthophoria, and exotropia ≤ 10 PD at the last visit. RESULTS: We included 45 patients, of whom 22 and 23 underwent two- and three-muscle surgery, respectively. The mean postoperative deviations were 9.5 and 2.7 PD in the two- and three-muscle groups, respectively; the overall success rates were 54.55% (12/22) and 91.30% (21/23). Subgroup analyses revealed that the surgical success rate of two-muscle operations was 66.67% (12/18) in 45–55 PD patients and 0% (0/4) in ≥ 55 PD patients; the success rates of three-muscle operations were 100% (7/7) and 87.50% (14/16). The success rate did not differ significantly between those with postoperative deviations of 45–55 PD (p = 0.137), but did between those who underwent two- and three-muscle operations to treat postoperative deviations of ≥ 55 PD (p = 0.003). CONCLUSIONS: Satisfactory results can be achieved via two-muscle surgery in patients with exotropia < 55 PD. However, for those with exotropia > 55 PD, three-muscle surgery is superior to two-muscle surgery. Therefore, large-angle exotropia is optimally treated via three-muscle surgery.
Esotropia ; Exotropia ; Follow-Up Studies ; Humans ; Retrospective Studies ; Strabismus