Novel CFTR Mutations in a Korean Infant with Cystic Fibrosis and Pancreatic Insufficiency

Cystic fibrosis (CF) is an autosomal recessive disease that is very rare in Asians: only a few cases have been reported in Korea. We treated a female infant with CF who had steatorrhea and failure to thrive. Her sweat chloride concentration was 102.0 mM/L. Genetic analysis identified two novel mutations including a splice site mutation (c.1766+2T>C) and a frameshift mutation (c.3908dupA; Asn1303LysfsX6). Pancreatic enzyme replacement and fat-soluble vitamin supplementation enabled the patient to get a catch-up growth. This is the first report of a Korean patient with CF demonstrating pancreatic insufficiency. CF should therefore be considered in the differential diagnosis of infants with steatorrhea and failure to thrive

Acute Effects of Asian Dust Events on Respiratory Symptoms and Peak Expiratory Flow in Children with Mild Asthma

The aim of this study was to investigate the possible adverse effects of Asian dust events on respiratory health in asthmatic children. Fifty-two children with mild asthma were studied for eight consecutive weeks in the spring of 2004 (March 8 to May 2). During the study period, five Asian dust days were identified; we included a lag period of two days following each of the events. Subjects recorded their respiratory symptom diaries and peak expiratory flow (PEF) twice daily during the study period; and they underwent methacholine bronchial challenge tests. The subjects reported a significantly higher frequency of respiratory symptoms during the Asian dust days than during the control days. They showed significantly more reduced morning and evening PEF values, and more increased PEF variability (10.1%±3.5% vs. 5.5%±2.2%) during the Asian dust days than during the control days. Methacholine PC20 was not significantly different between before and after the study period (geometric mean: 2.82 mg/mL vs. 3.16 mg/mL). These results suggest that the short-term Asian dust events might be associated with increased acute respiratory symptoms and changes in PEF outcomes. However, there might be little long-term influence on airway hyperresponsiveness in children with mild asthma

Mechanisims of asthma and allergic disease – 1086. Bacteria-derived extracellular vesicles as an important causative agent for asthma and COPD

Background Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometer-sized vesicles into the extracellular milieu, but it remains to be determined whether bacteria-derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases. We evaluated whether extracellular vesicles (EV) in indoor air are causally related to the pathogenesis of asthma and/or emphysema. Methods EV were prepared by sequential ultrafiltration and ultracentrifugation from indoor dust collected from a bed. Innate and adaptive immune responses were evaluated after once or 4 weeks airway exposure of EV, respectively. Results Vesicles 50-200 nm in diameter were present (102.5 microgram [based on protein concentration]/g dust) in indoor dust, and inhalation of 1 microgram of these vesicles for 4 weeks caused neutrophilic pulmonary inflammation. Additionally, polymyxin B (an antagonist of endotoxin, a cell wall component of Gram-negative bacteria) reversed the inflammation induced by the dust EV. Indoor dust harbors Esherichia coli-derived vesicles; airway exposure to the vesicles for 4 weeks induced neutrophilic inflammation and emphysema, which were partially eliminated by the absence of IFN-gamma or IL-17. Interestingly, serum dust EV-reactive IgG1 levels were significantly higher in atopic children with asthma than in atopic healthy children and those with rhinitis or dermatitis. Moreover, serum dust EV-reactive IgG1 levels were also elevated in adult asthma or COPD patients than in healthy controls. Conclusions EV in indoor dust, especially derived from Gram-negative bacteria, appear to be an important causative agent in the pathogenesis of asthma and/or emphysema

The role of inhaled and/or nasal corticosteroids on the bronchodilator response

PurposeTo compare the profiles of the bronchodilator response (BDR) among children with asthma and/or allergic rhinitis (AR) and to determine whether BDR in these children is reduced by treatment with inhaled and/or nasal corticosteroid.MethodsSixty-eight children with asthma (mean age, 10.9 years), 45 children with comorbid asthma and AR (mean age, 10.5 years), and 44 children with AR alone (mean age, 10.2 years) were investigated. After a 2-week baseline period, all children were treated with inhaled fluticasone propionate (either 100 or 250 µg b.i.d., tailored to asthma severity) or nasal fluticasone propionate (one spray b.i.d. in each nostril) or both, according to the condition. Before and 2 weeks after starting treatment, all children were evaluated with spirometry and bronchodilator testing. BDR was calculated as a percent change from the forced expiratory volume in 1 second (FEV1) at baseline.ResultsThe mean BDR was 10.3% [95% confidence interval (CI) 8.3-12.4%] in children with asthma, 9.0% (95% CI 7.3-10.9%) in subjects with asthma and AR, and 5.0% (95% CI 4.1-5.9%) in children with AR alone (P<0.001). After treatment, the mean BDR was reduced to 5.2% (95% CI 4.2-6.3%) (P<0.001) in children with asthma and to 4.5% (95% CI 3.5-5.5%) (P<0.001) in children with asthma and AR. However, children with rhinitis showed no significant change in BDR after treatment, with the mean value being 4.7% (95% CI 3.7-5.8%) (P=0.597).ConclusionThe findings of this study imply that an elevated BDR in children with AR cannot be attributed to nasal inflammation alone and highlights the close relationship between the upper and lower airways

Distributions of Antibody Titers to Mycoplasma pneumoniae in Korean Children in 2000-2003

The aim of study was to describe Mycoplasma pneumoniae epidemics in a hospital-based population. Special attention was paid to the relationship between antibody titer to M. pneumoniae and sex, age, and atopy. During the eight 6-month periods between January 2000 and December 2003, serum samples were obtained from 1,319 Korean children who presented with respiratory symptoms, and were examined for antibodies to M. pneumoniae using the indirect particle agglutination test. Geometric mean antibody titers peaked in the second half of 2000 and then decreased gradually, a second peak occurred in the second half of 2003. Likewise, the frequency of high antibody titers (≥1:640) also peaked during these two periods. Antibody titers in children aged 0-3 yr were lower than in older children during both peak periods and for 2 yr after the first peak. Sex and atopy had no effect on antibody titers. During the years 2000-2003, geometric mean antibody titers and the frequencies of high antibody titers varied with time. These changes suggest a cyclic pattern of M. pneumoniae infection, with two epidemic peaks separated by 3 yr

Early childhood wheezing: various natural courses and their relationship to later asthma

Wheezing is one of the most frequent complaints that lead to the use of medical resources in younger children. Generally, wheezing is caused by bronchiolitis and resolves spontaneously without recurrence, but sometimes, wheezing can progress into asthma. Early data on the natural history of childhood wheezing was mostly obtained from retrospective reviews of medical records or from questionnaires, which made it difficult to exclude biases. Now that many cohort studies are available, reviewing the results of birth cohort studies makes it possible to understand the natural course of early childhood wheezing and the risk factors for asthma. In this study, we have reviewed the various phenotypes of early childhood wheezing and their natural courses to help select the most appropriate management modalities for the different types of early childhood wheezing