Hyeon-Jong Yang

The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods.

BackgroundThis paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases.Methods/DesignThe participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child’s neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child’s genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6xa0months and every year until 10xa0years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child’s exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child’s neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child’s microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures.DiscussionThe COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.

Effects of Marathon Running on Cardiac Markers and Endothelin-1 in EIH Athletes

The aim of the present study was to determine the changes in cardiac makers and endothelin-1 (ET-1) in marathoners with exercise induced hypertension compared to normotensive controls before and after running a marathon. Among a total of 70 volunteers, 10 marathoners with systolic blood pressure (SBP) greater than 210 mmHg during a treadmill exercise stress test were selected as an exercise-induced hypertension group (EIH) and 10 marathoners with normal SBP were selected as a control group (CON). Blood was collected from all volunteers 2 h before and immediately after a marathon: creatinine kinase (CK), CK-MB, cardiac tropoin-I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and endothelin-1(ET-1). Cardiac markers, CK, CK-MB, and CK-MB/CK ratio significantly increased in both EIH and CON; significance was not observed between the groups. Significant increases were not observed in high sensitive-C reactive protein (hs-CRP) after the race nor between the groups. Significant increases in cTnI and NT-proBNP were observed after the race in both groups. In addition, EIH showed greater increase than CON after the race. In conclusion, increased vascular tone in EIH during a marathon increased blood pressure and myocardial burden which in turn increased myocardial cell membrane permeability to further increase myocardial tension to the point of cTnI release.

Interaction between 25-hydroxyvitamin D and variants at 17q12-21 on respiratory infections

25‐hydroxyvitamin D (25[OH]D) deficiency and genetic variants at the 17q12‐21 locus are independent risk factors for respiratory tract infections (RTIs). We aimed to investigate whether the effect of 25(OH)D at birth and 1 year of age and the polymorphism at the 17q12‐21 locus, or interactions between these two factors, increase susceptibility to RTIs in the first year of life.

Clinical characteristics of 2009 pandemic influenza A (H1N1) infection in children and the performance of rapid antigen test

Purpose In autumn 2009, the swine-origin influenza A (H1N1) virus spread throughout South Korea. The aims of this study were to determine the clinical characteristics of children infected by the 2009 H1N1 influenza A virus, and to compare the rapid antigen and real-time polymerase chain reaction (PCR) tests. Methods We conducted a retrospective review of patients ≥18 years of age who presented to Soonchunhyang University Hospital in Seoul with respiratory symptoms, including fever, between September 2009 and January 2010. A real-time PCR test was used to definitively diagnose 2009 H1N1 influenza A infection. Medical records of confirmed cases were reviewed for sex, age, and the time of infection. The decision to perform rapid antigen testing was not influenced by clinical conditions, but by individual factors such as economic conditions. Its sensitivity and specificity were evaluated compared to real-time PCR test results. Results In total, 934 patients tested positive for H1N1 by real-time PCR. The highest number of patients (48.9%) was diagnosed in November. Most patients (48.2%) were aged between 6 and 10 years. Compared with the H1N1 real-time PCR test results, the rapid antigen test showed 22% sensitivity and 83% specificity. Seventy-eight patients were hospitalized for H1N1 influenza A virus infection, and fever was the most common symptom (97.4%). Conclusion For diagnosis of 2009 H1N1 influenza A virus infection, the rapid antigen test was inferior to the real-time PCR test in both sensitivity and specificity. This outcome suggests that the rapid antigen test is inappropriate for screening.

Association of symptom control with changes in lung function, bronchial hyperresponsiveness, and exhaled nitric oxide after inhaled corticosteroid treatment in children with asthma

BACKGROUNDnA key therapeutic approach to asthma, which is characterized by chronic airway inflammation, is inhaled corticosteroid (ICS). This study evaluated the association of symptom control with changes in lung function, bronchial hyperresponsiveness (BHR), and exhaled nitric oxide (eNO) after ICS treatment in asthmatic children.nnnMETHODSnA total of 33 children aged between 5 and 12 years with mild to moderate persistent asthma were treated with 160xa0μg ciclesonide per day for 3 months. At days 0 and 90, the following parameters were assessed: asthma symptom scores; lung function, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%); BHR to methacholine and adenosine 5-monophosphate (AMP); and eNO.nnnRESULTSnAsthma symptom scores, lung function parameters, BHR to methacholine and AMP, and eNO levels at day 90 were significantly improved versus day 0 (all pxa0<xa00.001). Symptom scores at day 90 were not correlated with changes in lung function and BHR to methacholine during the follow-up period, whereas those at day 90 were more closely correlated with changes in BHR to AMP (rxa0=xa00.511, pxa0=xa00.003) than with eNO (rxa0=xa0-0.373, pxa0=xa00.035). Additionally, changes in PC20 AMP were correlated with changes in PC20 methacholine (rxa0=xa00.451, pxa0=xa00.011) and eNO (rxa0=xa0-0.474, pxa0=xa00.006).nnnCONCLUSIONSnChanges in the BHR to AMP, and to a lesser extent eNO, correlate with asthma symptom control after ICS treatment. BHR to AMP may better reflect the relationship between improved airway inflammation due to ICS treatment and asthma symptoms.

Pollen-Food Allergy Syndrome in Korean Pollinosis Patients: A Nationwide Survey

Purpose Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergy in pollinosis patients caused by raw fruits and vegetables and is the most common food allergy in adults. However, there has been no nationwide study on PFAS in Korea. In this study, we investigated the prevalence and clinical characteristics of PFAS in Korea. Methods Twenty-two investigators participated in this study, in which patients with allergic rhinoconjunctivitis and/or bronchial asthma with pollen allergy were enrolled. The questionnaires included demographic characteristics, a list of fruits and vegetables, and clinical manifestations of food allergy. Pollen allergy was diagnosed by skin prick test and/or measurement of the serum level of specific IgE. Results A total of 648 pollinosis patients were enrolled. The prevalence of PFAS was 41.7% (n = 270). PFAS patients exhibited cutaneous (43.0%), respiratory (20.0%), cardiovascular (3.7%) or neurologic symptoms (4.8%) in addition to oropharyngeal symptoms. Anaphylaxis was noted in 8.9% of the PFAS patients. Seventy types of foods were linked to PFAS; e.g., peach (48.5%), apple (46.7%), kiwi (30.4%), peanut (17.4%), plum (16.3%), chestnut (14.8%), pineapple (13.7%), walnut (14.1%), Korean melon (12.6%), tomato (11.9%), melon (11.5%) and apricot (10.7%). Korean foods such as taro/taro stem (8.9%), ginseong (8.2%), perilla leaf (4.4%), bellflower root (4.4%), crown daisy (3.0%), deodeok (3.3%), kudzu root (3.0%) and lotus root (2.6%) were also linked to PFAS. Conclusions This was the first nationwide study of PFAS in Korea. The prevalence of PFAS was 41.7%, and 8.9% of the PFAS patients had anaphylaxis. These results will provide clinically useful information to physicians.

A novel BTK gene mutation, c.82delC (p.Arg28 Alafs*5), in a Korean family with X-linked agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Bruton’s tyrosine kinase (BTK) gene mutations. These mutations cause defects in B-cell development, resulting in the virtual absence of these lymphocytes from the peripheral circulation. Consequently, this absence leads to a profound deficiency of lg all isotypes, and an increased susceptibility to encapsulated bacterial infections. A 15-month-old Korean boy presented with recurrent sinusitis and otitis media after 6 months of age, and had a family history of 2 maternal uncles with XLA. Laboratory tests revealed a profound deficiency of Ig isotypes, and a decreased count of CD19+ B cells in the peripheral circulation. Based on his family history and our laboratory test results, he was diagnosed with XLA. We performed BTK gene analysis of peripheral blood samples obtained from family members to confirm the diagnosis. Mutational analysis revealed a novel hemizygous frameshift mutation (c.82delC, p.Arg28Alafs*5), in the BTK gene. His mother and maternal grandmother were heterozygous carriers of this mutation and his two maternal uncles were hemizygous at the same position. After XLA diagnosis, intravenous immunoglobulin (400 mg/kg, monthly) treatment was initiated; recurrent sinusitis and otitis media were subsequently brought under control. To our knowledge, this is the first reported case of a Korean pedigree with a novel mutation in the BTK gene.