Laura Bolling

The Role of Extraesophageal Reflux in Otitis Media in Infants and Children

Objectives/Hypothesis: Gastroesophageal reflux disease (GERD) is common in children, and extraesophageal reflux disease (EORD) has been implicated in the pathophysiology of otitis media (OM). We sought to 1) determine the incidence of pepsin/pepsinogen presence in the middle ear cleft of a large sample of pediatric patients undergoing myringotomy with tube placement for OM; 2) compare this with a control population of pediatric patients undergoing middle ear surgery (cochlear implantation) with no documented history of OM; 3) analyze potential risk factors for OM in children with EORD demonstrated by the presence of pepsin in the middle ear cleft; and 4) determine if pepsin positivity at the time of myringotomy with tube placement predisposes to posttympanostomy tube otorrhea.

Assessment of the prevalence of microaspiration by gastric pepsin in the airway of ventilated children

Aim: Mechanically ventilated patients are at risk for aspiration of gastric contents. The aim of this observational study was to determine the prevalence of micro‐aspiration in children with cuffed and uncuffed endotracheal (ET) tubes and with tracheostomies and to assess the effect of feeding status on aspiration. Micro‐aspiration was determined by measuring gastric pepsin in tracheal aspirates.

Detection of Gastric Pepsin in Middle Ear Fluid of Children with Otitis Media

OBJECTIVE: We sought to confirm the finding of pepsin/pepsinogen in the middle ear fluid of children with otitis media in a larger sample size using a sensitive and specific pepsin assay. STUDY DESIGN AND SETTING: We evaluated 152 children (225 ear samples) in a prospective study at a tertiary care childrens hospital. The presence of pepsin in middle ear aspirates was determined using enzymatic assay. RESULTS: Of the patients, 14.4 percent (22 of 152) had detectable pepsin activity in one or both of the ear samples with no pepsin activity detected in control serum. Average pepsin concentration in the samples was 96.6 ± 170.8 ng/ml, ranging from 13 to 687 ng/ml. Pepsin concentration in the middle ear of children younger than 1.0 year was significantly higher than in older age groups. CONCLUSION AND SIGNIFICANCE: Results indicate that pepsin/pepsinogen is present in the middle ears of children with otitis media, although not at the high rate previously reported. Gastric reflux may be one causative factor in the pathogenesis of otitis media.

The Role of Gastric Pepsin in the Inflammatory Cascade of Pediatric Otitis Media

IMPORTANCE Otitis media is characterized as an ongoing inflammation with accumulation of an effusion in the middle ear cleft. The molecular mechanisms underlying the pathogenesis, particularly the inflammatory response, remain largely unknown. We hypothesize that aspiration of gastric contents into the nasopharynx may be responsible for the initiation of the inflammatory process or aggravate a preexisting condition. OBJECTIVE To investigate the correlation of gastric pepsin A with inflammatory cytokines, bacterial infection, and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 129 pediatric patients undergoing myringotomy with tube placement for otitis media at a tertiary care pediatric hospital. MAIN OUTCOMES AND MEASURES Ear samples were tested for pepsin A; cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor; and bacterial culture inoculation. Data were analyzed by descriptive statistics and regression analysis to identify risk factors for the presence of pepsin A and to correlate pepsin A levels with cytokine levels, infection status, and clinical outcomes. RESULTS Of the 129 patients, 199 ear samples were obtained; 82 samples (41%) and 64 patients (50%) were positive for pepsin A as measured by immunoassay. Pepsin A positivity correlated with age younger than 3.0 years (mean [SD], 2.3 [2.1] years in the positive group vs 3.3 [3.0] years in the negative group) and with all 3 cytokine levels (mean [SD] tumor necrosis factor, 29.5 [45.9] pg/mL in the positive group vs 13.2 [21.6] pg/mL in the negative group; IL-6, 6791.7 [9389.1] pg/mL in the positive group vs 2849.9 [4066.3] pg/mL in the negative group; and IL-8, 6828.2 [8122.3] pg/mL in the positive group vs 2925.1 [3364.5] pg/mL in the negative group [all P < .05]); however, logistic regression analysis showed that only IL-8 (odds ratio, 3.96; 95% CI, 1.3-12.0; P = .02) and age (odds ratio, 3.83; 95% CI, 1.2-12.7; P = .03) were significant independent variables. No statistically significant association was found with other parameters. Multiple linear regressions revealed that the levels of pepsin A were correlated with IL-8 levels (R2 = 0.248; P < .001) and the need for second or third tubes 6 to 12 months after the first (R2 = 0.102; P = .006). The presence of pepsin A in the middle ear was not associated with increased bacterial infection. Interleukin 8 was independent and significantly associated with both pepsin A levels and bacterial infection (R2 = 0.144 and 0.263, respectively; P = .001 for both). CONCLUSIONS AND RELEVANCE Extraesophageal reflux as indicated by the presence of pepsin A is closely involved in the middle ear inflammatory process and may worsen the disease in some children; however, a proof of cause and effect between extraesophageal reflux and middle ear inflammation requires further investigation.

An Automated Method for the Determination of Intestinal Disaccharidase and Glucoamylase Activities

Determination of disaccharidase and glucoamylase activities is important for the diagnosis of intestinal diseases. We adapted a widely accepted manual method to an automated system that uses the same reagents reaction volumes, incubation times, and biopsy size as the manual method. A dye was added to the homogenates as the internal quality control to monitor the pipetting precision of the automated system. When the automated system was tested using human intestinal homogenates, the activities of all the routinely tested disaccharidases, including lactase, maltase, sucrase, and palatinase, as well as the activity of glucoamylase, showed perfect agreement with the manual method and were highly reproducible. The automated analyzer can perform the same routine assays of disaccharidases and glucoamylase with high consistency and accuracy and reduce testing costs by performing a larger sample size with the same number of staff. Additional developments, such as barcoding and built-in plate reading, would result in a completely automated system.

A Pilot Randomized Clinical Trial Assessing the Effect of Cricoid Pressure on Risk of Aspiration.

Patients at risk for microaspiration during elective intubation often receive cricoid pressure in the hopes of mitigating such risk. However, there is scarce evidence to either support or reject this practice. The objective of this investigation was to assess the effect of cricoid pressure on microaspiration and to inform the potential feasibility of conducting a larger, more definitive clinical trial.

W1838 Micro-Aspiration and Stability of Gastric Pepsin

Background Typical symptoms of gastroesophageal reflux disease (GERD) are heartburn and regurgitation. Extraesophageal (EE) symptoms such as cough and throat clearing are less commonly associated with GERD but represent a common presenting symptom for reflux testing. Proximal extent of refluxate into the larynx or even the lungs is proposed as a potential mechanism for EE symptoms. Aim We tested the hypothesis that EE symptoms are more frequently associated with proximal esophageal reflux than typical symptoms. Methods A blinded assessment was rigorously applied. Themultichannel intraluminal impedance-pH (MII-pH) tracings analyzed for this study were edited by one of the investigators so that none of the symptom markers were visible and the reflux associated symptoms reviewed were simply marked as symptom 1-5 for each patient. 815 consecutive MII-pH reports were reviewed to identify 40 patients with at least 5 symptom events preceded by a reflux episode, thus a total of 50 reflux related events in each of 4 symptom groups: cough, throat clearing, heartburn, and regurgitation. A second investigator blindly analyzed all 200 episodes by reporting the extent of the refluxate at 7, 9, 15, and 17 cm above the LES. Results The percentage of symptom related reflux extending proximally to 17 cm above the LES is similar among all four symptom types (Figure 1). At least 50% of all symptoms were associated with proximal reflux to 17 cm above the LES, with the numerically highest being regurgitation (60%). There is no significant difference between any of the values. Conslusion This study confirms the frequent association of proximal reflux with GERDrelated symptoms previously identified. However, as opposed to common beliefs, our data indicate that EE GERD-related symptoms are not more frequently associated with proximal reflux than typical GERD symptoms. Both EE and esophageal symptoms are associated with reflux to 17cm at least 50% of the time.