Gene-environment interaction between Toll-like receptor 4 and mold exposure in the development of atopic dermatitis in preschool children

PURPOSE: Genetic factors and environmental exposures are recognized as important risk factors for atopic dermatitis (AD) in children. Inflammatory responses by molds can be mediated via Toll-like receptor 4 (TLR4). The aims of this study were to investigate mold as risk factor of AD and gene-environment interaction on AD in preschool children. METHODS: We undertook a cross-sectional survey with 986 preschool children. We investigated five mold exposure measures (dampness stain, dampness damage, visible mold, mold odor, and house repair). The TLR4 polymorphism (rs1927911) was genotyped by TaqMan assay. RESULTS: The prevalence of AD was as follows: AD diagnosis by questionnaire, 35.1%; current AD (lifetime diagnosis together with symptoms in the last 12 months), 21.5%. When children with parental history of AD were exposed to mold odor during infancy and house repair during the last 12 months, the risk for current AD (adjusted odds ratio [aOR], 6.826; 95% confidence interval [CI], 2.511 to 18.554 vs. aOR, 6.143; 95% CI, 2.348 to 16.074) was further increased than only with parental history of AD. In children with the CC genotype of TLR4 polymorphism, the risk of AD was increased by mold exposure. CONCLUSION: This investigation identified that mold exposure is potential risk factor for AD in preschool children. Parental history of AD and mold exposure during infancy and the last 12 months had synergistic effect on high prevalence of AD. We identified that mold exposure and TLR4 polymorphism have an effect on the development of atopic dermatitis.

Epidemic acute interstitial pneumonia in children occurred during the early 2006s / 소아과

PURPOSE: This study was aimed to analyze the clinical characteristics of patients with acute interstitial pneumonia who had presented similar clinical patterns from March to June, 2006 and to describe our experience of treatment and to identify risk factors associated with prognosis. METHODS: The clinical characteristics, radiologic and histopathologic findings and response to steroids of 15 patients (non-survival group [n=7] and survival group [control, n=8]) with acute interstitial pneumonia were investigated through the review of medical records. RESULTS: The mean age of the patients was 26 (range: 3-48) months. Cough, cyanosis and fever were frequent symptoms. The most frequent radiologic findings on admission were pneumomediastium and extensive ground glass opacity. Surgical lung biopsy was performed on 8/15 (53.3%) patients and diffuse alveolar damage was found. Mechanical ventilation was applied for 9/15 (60.0%) patients for 40 (range: 1-99) days. Five patients in survival group received steroid treatment and 7 patients in non-survivial group (P=0.20). One patient in survival group received steroid pulse treatment and 4 patients in non-survival group (P=0.12). Seven patients died all of respiratory failure. The survival rate was 53.4%. CONCLUSION: The patients with acute interstitial pneumonia which occurred on spring 2006 showed high mortality because of rapidly and extensively progressing pulmonary fibrosis and air leakage. Therefore, we should consider surgical lung biopsy and steroid application earlier. We should recognize this acute interstitial pneumonia occurring on spring in domestics and need to investigate the cause and treatment in large scale.

A Case of Congenital Pulmonary Vein Stenosis Diagnosed in an Infant with Recurrent Hemoptysis / 소아알레르기및호흡기학회지

Congenital pulmonary vein stenosis is a rare cardiac malformation with a poor prognosis and is not easy to diagnose, because symptoms emerge in infants accompanying progressively worsening pulmonary hypertension. A nine-month-old infant visited our hospital due to recurrent respiratory infections and hemoptysis. He was diagnosed with congenital pulmonary vein stenosis by cardiac catheterization. Cardiac catheterization findings revealed that two pulmonary veins were stenotic and one pulmonary vein was occluded. Pulmonary artery catheterization showed the evidence of severe pulmonary hypertension with a mean pulmonary artery pressure of 55 mmHg and a pulmonary artery wedge pressure of 30 mmHg. Due to the aggravation of pulmonary hypertension symptoms, we performed sutureless pericardial marsupialization to reduce the obstruction and the restenosis, but he died a week. In cases of infants with recurrent hemoptysis, we should rule out congenital pulmonary vein stenosis.

Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+increase are reciprocally modulated in rat cardiomyocytes

Doxorubicin (DOX) is one of the most potent anticancer drugs and induces acute cardiac arrhythmias and chronic cumulative cardiomyopathy. Though DOX-induced cardiotoxicity is known to be caused mainly by ROS generation, a disturbance of Ca2+ homeostasis is also implicated one of the cardiotoxic mechanisms. In this study, a molecular basis of DOX-induced modulation of intracellular Ca2+ concentration ([Ca2+]i) was investigated. Treatment of adult rat cardiomyocytes with DOX increased [Ca2+]i irrespectively of extracellular Ca2+, indicating DOX-mediated Ca2+ release from intracellular Ca2+ stores. The DOX-induced Ca2+ increase was slowly processed and sustained. The Ca2+ increase was inhibited by pretreatment with a sarcoplasmic reticulum (SR) Ca2+ channel blocker, ryanodine or dantrolene, and an antioxidant, alpha-lipoic acid or alpha-tocopherol. DOX-induced ROS generation was observed immediately after DOX treatment and increased in a time-dependent manner. The ROS production was significantly reduced by the pretreatment of the SR Ca2+ channel blockers and the antioxidants. Moreover, DOX-mediated activation of caspase-3 was significantly inhibited by the Ca2+ channel blockers and a-lipoic acid but not a-tocopherol. In addition, cotreatment of ryanodine with alpha-lipoic acid resulted in further inhibition of the casapse-3 activity. These results demonstrate that DOX-mediated ROS opens ryanodine receptor, resulting in an increase in [Ca2+]i and that the increased [Ca2+]i induces ROS production. These observations also suggest that DOX/ROS-induced increase of [Ca2+]i plays a critical role in damage of cardiomyocytes.