IL-8 regulates mucin gene expression at the posttranscriptional level in lung epithelial cells.

Airway inflammation and mucus hypersecretion/overproduction/obstruction are pathophysiological characteristics of cystic fibrosis, asthma, and chronic obstructive pulmonary disease. Up-regulation of airway mucin genes by inflammatory/immune response mediators is one of the major contributors to mucin overproduction. IL-8, a potent proinflammatory mediator and neutrophil chemoattractant, is present at high levels in the airway secretions of such patients. In this study, the effects of IL-8 on expression of two major airway mucin genes, MUC5AC and MUC5B, were evaluated. IL-8 increased the mRNA abundance of both mucin genes in two human respiratory tract-derived cell lines (A549 and NCI-H292) in a time- and concentration-dependent manner. IL-8 also increased MUC5AC and MUC5B mRNA levels in primary normal differentiated human bronchial epithelial cells, with a high concentration of IL-8 required to increase MUC5B mRNA levels. IL-8 did not transcriptionally up-regulate MUC5AC gene expression, but rather increased the stability of the MUC5AC transcript, suggesting regulation at the posttranscriptional level. In addition, IL-8 altered the levels of RNA-binding proteins to specific domains in the 3'-untranslated region of the MUC5AC transcript. Taken together, these data indicate that the IL-8-induced binding of RNA-binding proteins to the 3'-untranslated region of MUC5AC is a potential mechanism for regulating MUC5AC gene expression at the posttranscriptional level, thus suggesting a new role whereby IL-8 sustains mucin gene expression in inflamed airways.

Discordance in interpretation of chest radiographs between pediatric intensivists and a radiologist: impact on patient management.

PURPOSE: When radiologists are not available, chest radiographs (CXRs) of pediatric intensive care unit (PICU) patients are commonly interpreted by pediatric intensivists. We prospectively investigated the frequency of errors in CXR interpretation by pediatric intensivists and their impact on patient management. MATERIALS AND METHODS: Chest radiographs of PICU patients were evaluated by 5 pediatric intensivists then by a pediatric radiologist (the "gold standard"). If the interpretation of the radiologist and intensivist differed, an independent intensivist determined whether a management change took place. A pediatric pulmonologist determined how many intensivist interpretations were different from the radiologist's interpretations. RESULTS: Seven hundred twenty-eight radiographic findings were identified by the radiologist in 460 CXRs. There were 33 interpretation errors by the intensivists (4.5% of the findings in 7.1% of the CXRs). Only 3/33 error corrections (0.45% of the findings in 0.7% of the CXRs) resulted in change in patient management. CONCLUSIONS: Errors in interpretation of CXRs by pediatric intensivists were common but less than that in other series, probably because of education of the pediatric intensivists through daily rounds with the radiologist. Although interpretation errors that affected patient management were rare, their clinical importance supports the growing practice of 24/7 remote radiograph reading by radiologists.