Development and clinical feasibility of a reduced-dose radiograph in children for feeding tube placement.

BACKGROUND: Temporary feeding tubes are commonly used but may lead to complications if malpositioned. Radiographs are the gold standard for assessing tube position, but clinician concern over radiation risks may curtail their use. OBJECTIVE: We describe development and use of a reduced dose feeding tube radiograph (RDFTR) targeted for evaluation of feeding tube position. MATERIALS AND METHODS: Age-based abdominal radiograph was adapted to use the lowest mAs setting of 0.32 mAs with field of view between carina and iliac crests. The protocol was tested in DIGI-13 line-pair plates and anthropomorphic phantoms. Retrospective review of initial clinical use compared dose area product (DAP) for RDFTR and routine abdomen, chest, or infant chest and abdomen. Review of RDFTR reports assessed tube visibility, malpositioning, and incidental critical findings. RESULTS: Testing through a line-pair phantom showed loss of spatial resolution from 2.2 line pairs to 0.6 line pairs but preserved visibility of feeding tube tip in RDFTR protocol. DAP comparisons across 23,789 exams showed RDFTR reduced median DAP 72-93% compared to abdomen, 55-78% compared to chest, and 76-79% compared to infant chest and abdomen (p<0.001). Review of 3286 reports showed tube was visible in 3256 (99.1%), malpositioned in airway 8 times (0.2%) and in the esophagus 74 times (2.3%). The tip was not visualized in 30 (0.9%). Pneumothorax or pneumoperitoneum was noted seven times (0.2%) but was expected or spurious in five of these cases. CONCLUSION: RDFTR significantly reduces radiation dose in children with temporary feeding tubes while maintaining visibility of tube tip.

Using metabolic potential within the airway microbiome as predictors of clinical state in persons with cystic fibrosis.

Introduction: Pulmonary exacerbations (PEx) in persons with cystic fibrosis (CF) are primarily related to acute or chronic inflammation associated with bacterial lung infections, which may be caused by several bacteria that activate similar bacterial genes and produce similar by-products. The goal of our study was to perform a stratified functional analysis of bacterial genes at three distinct time points in the treatment of a PEx in order to determine the role that specific airway microbiome community members may play within each clinical state (i.e., PEx, end of antibiotic treatment, and follow-up). Our secondary goal was to compare the change between clinical states with the metabolic activity of specific airway microbiome community members. Methods: This was a prospective observational study of persons with CF treated with intravenous antibiotics for PEx between 2016 and 2020 at Children's National Hospital. Demographic and clinical information as well as respiratory samples were collected at hospital admission for PEx, end of antibiotic treatment, and follow-up. Metagenomic sequencing was performed; MetaPhlAn3 and HUMANn3 were used to assign sequences to bacterial species and bacterial metabolic genes, respectively. Results: Twenty-two persons with CF, with a mean age of 14.5 (range 7-23) years, experienced 45 PEx during the study period. Two-hundred twenty-one bacterial species were identified in the respiratory samples from the study cohort. Ten bacterial species had differential gene abundance across changes in the clinical state including Staphylococcus aureus, Streptococcus salivarius, and Veillonella atypica (all padj < 0.01 and log2FoldChange > |2|). These corresponded to a differential abundance of bacterial genes, with S. aureus accounting for 81% of the genes more abundant in PEx and S. salivarius accounting for 83% of the genes more abundant in follow-up, all compared to the end of treatment. Lastly, 8,653 metabolic pathways were identified across samples, with again S. aureus and S. salivarius contributing to the differential abundance of pathways (106 in PEx vs. 66 in follow-up, respectively). V. atypica was associated with a single metabolic pathway (UDP-N-acetyl-D-glucosamine biosynthesis) increased in follow-up compared to PEx. Discussion: Taken together, these data suggest that the metabolic potential of bacterial species can provide more insight into changes across clinical states than the relative abundance of the bacteria alone.

Microarray analysis identifies defects in regenerative and immune response pathways in COPD airway basal cells.

BACKGROUND: Airway basal cells are specialised stem cells and regenerate airway epithelium. Airway basal cells isolated from patients with COPD regenerate airway epithelium with an abnormal phenotype. We performed gene expression analysis to gain insights into the defective regenerative programme in COPD basal cells. METHODS: We conducted microarray analysis and compared COPD versus normal basal cells to identify differentially regulated genes (DEGs) and the enriched biological pathways. We determined the correlation of DEGs with cell polarisation and markers of ciliated and goblet cells. HOXB2 was knocked down in 16HBE14o- cells and monitored for polarisation of cells. HOXB2 expression in the lung sections was determined by immunofluorescence. RESULTS: Comparison of normal and COPD basal cell transcriptomic profiles highlighted downregulation of genes associated with tissue development, epithelial cell differentiation and antimicrobial humoral response. Expression of one of the tissue development genes, HOXB2 showed strong correlation with transepithelial resistance and this gene was downregulated in COPD basal cells. Knockdown of HOXB2, abrogated polarisation of epithelial cells in normal cells. Finally, HOXB2 expression was substantially reduced in the bronchial epithelium of COPD patients. CONCLUSIONS: Defect in gene signatures involved in tissue development and epithelial differentiation were implicated in COPD basal cells. One of the tissue developmental genes, HOXB2, is substantially reduced in bronchial epithelium of COPD patients. Since HOXB2 contributes to airway epithelial cell polarisation, we speculate that reduced expression of HOXB2 in COPD may contribute to abnormal airway epithelial regeneration in COPD.