Feeding Interventions Are Associated With Improved Outcomes in Children With Laryngeal Penetration.

OBJECTIVES: To determine if children with laryngeal penetration on videofluoroscopic swallow study (VFSS) who received feeding interventions (thickened liquids, change in liquid flow rate, and/or method of liquid delivery) had improved symptoms and decreased hospitalizations compared with those without intervention. METHODS: We performed a retrospective cohort study of children under 2 years with laryngeal penetration on VFSS at our institution in 2015 to determine initial and follow-up VFSS findings, symptom improvement at follow-up, and hospitalization risk before and after VFSS. Proportions were compared with Fisher exact test and hospitalizations with paired t tests. RESULTS: We evaluated 137 subjects with age 8.93 ±â€Š0.59 months who had laryngeal penetration without aspiration on VFSS. Fifty-five percent had change in management, with 40% receiving thickening and 15% a change in flow rate. There was significant improvement in symptoms for children that had feeding intervention and this improvement was the greatest with thickening (OR 41.8, 95% CI 12.34-141.69, P < 0.001). On repeat VFSS, 26% had evidence of aspiration that was not captured on initial VFSS. Subjects had decreased total and pulmonary hospitalizations with feeding intervention and decreased pulmonary nights with thickening (P < 0.05). CONCLUSIONS: Laryngeal penetration appears to be clinically significant in children with oropharyngeal dysphagia and interventions to decrease its occurrence are associated with improved outcomes including decreased symptoms of concern and hospitalization nights. Thickening or other feeding intervention should be considered for all symptomatic children with laryngeal penetration on swallow study.

Metabolomic profiling of extraesophageal reflux disease in children.

Although respiratory symptoms in children are often attributed to gastroesophageal reflux disease, establishing a clear diagnosis of extraesophageal reflux disease (EERD) can be challenging, as there are no sensitive or specific EERD biomarkers. The aim of this study was to evaluate the metabolite profile in bronchoalveolar (BAL) fluid from children with suspected EERD and assess the impact of reflux treatment on these metabolites. In this prospective pilot study, we performed nontargeted global metabolomic profiling on BAL fluid from 43 children undergoing testing with bronchoscopy, upper endoscopy, and multichannel intraluminal impedance with pH (pH-MII) for evaluation of chronic respiratory symptoms. Twenty-three (54%) patients had an abnormal pH-MII study. Seventeen (40%) patients were on proton pump inhibitors (PPIs) for testing. Levels of histamine, malate, adenosine 5'-monophosphate, and ascorbate were significantly lower in subjects with abnormal pH-MII studies compared to those normal studies. Furthermore, in children off PPI therapy, those with abnormal pH-MII studies had robust increases in a number of glycerophospholipids within phospholipid metabolic pathways, including derivatives of glycerophosphorylcholine, glycerophosphoglycerol, and glycerophosphoinositol, compared to those with normal pH-MII studies. These findings offer insight into the impact of reflux and PPIs on the lungs and provide a foundation for future studies using targeted metabolomic analysis to identify potential biomarkers of EERD.

Aerodigestive sampling reveals altered microbial exchange between lung, oropharyngeal, and gastric microbiomes in children with impaired swallow function.

BACKGROUND: Children with oropharyngeal dysphagia have impaired airway protection mechanisms and are at higher risk for pneumonia and other pulmonary complications. Aspiration of gastric contents is often implicated as a cause for these pulmonary complications, despite being supported by little evidence. The goal of this study is to determine the relative contribution of oropharyngeal and gastric microbial communities to perturbations in the lung microbiome of children with and without oropharyngeal dysphagia and aspiration. METHODS: We conducted a prospective cohort study of 220 patients consecutively recruited from a tertiary aerodigestive center undergoing simultaneous esophagogastroduodenoscopy and flexible bronchoscopy. Bronchoalveolar lavage, gastric and oropharyngeal samples were collected from all recruited patients and 16S sequencing was performed. A subset of 104 patients also underwent video fluoroscopic swallow studies to assess swallow function and were categorized as aspiration/no aspiration. To ensure the validity of the results, we compared the microbiome of these aerodigestive patients to the microbiome of pediatric patients recruited to a longitudinal cohort study of children with suspected GERD; patients recruited to this study had oropharyngeal, gastric and/or stool samples available. The relationships between microbial communities across the aerodigestive tract were described by analyzing within- and between-patient beta diversities and identifying taxa which are exchanged between aerodigestive sites within patients. These relationships were then compared in patients with and without aspiration to evaluate the effect of aspiration on the aerodigestive microbiome. RESULTS: Within all patients, lung, oropharyngeal and gastric microbiomes overlap. The degree of similarity is the lowest between the oropharynx and lungs (median Jensen-Shannon distance (JSD) = 0.90), and as high between the stomach and lungs as between the oropharynx and stomach (median JSD = 0.56 for both; p = 0.6). Unlike the oropharyngeal microbiome, lung and gastric communities are highly variable across people and driven primarily by person rather than body site. In patients with aspiration, the lung microbiome more closely resembles oropharyngeal rather than gastric communities and there is greater prevalence of microbial exchange between the lung and oropharynx than between gastric and lung sites (p = 0.04 and 4x10-5, respectively). CONCLUSIONS: The gastric and lung microbiomes display significant overlap in patients with intact airway protective mechanisms while the lung and oropharynx remain distinct. In patients with impaired swallow function and aspiration, the lung microbiome shifts towards oropharyngeal rather than gastric communities. This finding may explain why antireflux surgeries fail to show benefit in pediatric pulmonary outcomes.

Progression of hair cell ejection and molecular markers of apoptosis in the avian cochlea following gentamicin treatment.

Aminoglycoside treatment induces caspase-dependent apoptotic death in inner ear sensory hair cells. The timing of apoptotic signaling in sensory hair cells following systemic aminoglycoside treatment has not been characterized in vivo. We administered a single subcutaneous injection of the aminoglycoside gentamicin (300 mg/kg) to 12-16-day-old chicks and used immunocytochemical techniques to document the following responses in affected hair cells: T-cell restricted intracellular antigen-related protein (TIAR) translocation from the nucleus to the cytoplasm, cytochrome c release from the mitochondria, caspase-3 activation, nuclear condensation, and an orderly progression of hair cell ejection from the proximal end of the basilar papilla. Hair cells in the proximal tip exhibited TIAR translocation from the nucleus and aggregation into punctate granules in the cytoplasm 12 hours after injection and the response progressed distally. Cytochrome c release from the mitochondria into the cytoplasm and caspase-3 activation were observed in affected hair cells immediately prior to and during ejection. Hair cell ejection occurred between 30 and 54 hours after injection, beginning in the proximal tip and progressing distally. Nuclear condensation accompanied ejection while the loss of: 1) membrane integrity; 2) phalloidin labeling of F-actin; and 3) TO-PRO-1 labeling of nuclear contents occurred within 48 hours following ejection. Our results present a timeline of aminoglycoside-induced inner ear sensory hair cell apoptotic death that includes an 18-hour window between the initial apoptotic response and the later stages of programmed death signaling that accompany ejection and a gradual breakdown of hair cells following ejection.