Objectives To test the hypothesis that PPI use results in changes in gastric microflora which, through full column reflux, results in lung and oropharyngeal microflora changes. Study design We performed a prospective, cross sectional cohort study of 116 children (57 off and 59 on PPIs) undergoing simultaneous bronchoscopy and upper endoscopy for the evaluation of chronic cough. We performed 16S sequencing on gastric, bronchoalveolar lavage and oropharyngeal fluid. Fifty patients also underwent multichannel intraluminal impedance (pH-MII) testing. Results Streptococcus was more abundant in the gastric fluid of patients taking proton pump inhibitors (PPIs) and there was a significant correlation with PPI dose (mg/kg/day) and abundance of gastric Streptococcus (p=0.01). There was also a significant difference in the abundance of oropharyngeal Streptococcus in PPI treated patients. Eight unique bacterial genera were found in the gastric and lung fluid but not in the oropharyngeal suggesting exchange between the two sites and two of the seven (Lactococcus, Acinetobacter) were more abundant in patients with more full column reflux, suggesting direct aspiration. Principal component analysis revealed greater overlap between gastric and lung than oropharyngeal microflora. Conclusions PPI use was associated with differences in gastric, lung and oropharyngeal microflora. Although microflora exchange can occur between all three sites, gastric and lung microflora are more closely related and the mechanism of exchange between sites may be aspiration of full column reflux.

The use of acid suppression has been associated with an increased risk of upper and lower respiratory tract infections in the outpatient setting but the mechanism behind this increased risk is unknown. We hypothesize that this infection risk results from gastric bacterial overgrowth with subsequent seeding of the lungs.OBJECTIVES To determine if acid-suppression use results in gastric bacterial overgrowth, if there are changes in lung microflora associated with the use of acid suppression, and if changes in lung microflora are related to full-column nonacid gastroesophageal reflux. DESIGN, SETTING, AND PARTICIPANTSA 5-year prospective cohort study at a tertiary care center where children ages 1 to 18 years were undergoing bronchoscopy and endoscopy for the evaluation of chronic cough. Acid-suppression use was assessed through questionnaires with confirmation using an electronic medical record review. MAIN OUTCOMES AND MEASURESOur primary outcome was to compare differences in concentration and prevalence of gastric and lung bacteria between patients who were and were not receiving acid-suppression therapy. We compared medians using the Wilcoxon signed rank test and determined prevalence ratios using asymptotic standard errors and 95% confidence intervals. We determined correlations between continuous variables using Pearson correlation coefficients and compared categorical variables using the Fisher exact test.RESULTS Forty-six percent of patients taking acid-suppression medication had gastric bacterial growth compared with 18% of untreated patients (P = .003). Staphylococcus (prevalence ratio, 12.75 [95% CI, 1.72-94.36]), Streptococcus (prevalence ratio, 6.91 [95% CI, 1.64-29.02]), Veillonella (prevalence ratio, 9.56 [95% CI, 1.26-72.67]), Dermabacter (prevalence ratio, 4.78 [95% CI, 1.09-21.02]), and Rothia (prevalence ratio, 6.38 [95% CI, 1.50-27.02]) were found more commonly in the gastric fluid of treated patients. The median bacterial concentration was higher in treated patients than in untreated patients (P = .001). There was no difference in the prevalence (P > .23) of different bacterial genera or the median concentration of total bacteria (P = .85) in the lungs between treated and untreated patients. There were significant positive correlations between proximal nonacid reflux burden and lung concentrations of Bacillus

Objectives To determine the sensitivity of salivary pepsin compared with multichannel intraluminal impedance with pH testing (pH-MII), endoscopy, and gastroesophageal reflux disease (GERD) questionnaires. Study design We prospectively recruited 50 children from Boston Children’s Hospital, who were undergoing pH-MII to evaluate for GERD. Patients completed 24 hour pH-MII testing, symptom and quality of life questionnaires, and provided a saliva specimen which was analyzed using the PepTest® lateral flow test. A subset of patients also underwent bronchoscopy and esophagogastroduodenoscopy. ROC analyses were performed to determine the sensitivity of salivary pepsin compared with each reference standard. Results 21 patients (42%) were salivary pepsin positive, with median concentration of pepsin in the saliva 10 ng/mL (IQR 10 – 55). There was no significant difference in the distributions of acid, nonacid, total reflux episodes, full column reflux or any other reflux variable in patients that were pepsin positive compared with pepsin negative (p>0.5). There was no significant correlation between the number of reflux episodes and pepsin concentrations (p>0.1). There was no positive relationship between salivary pepsin positivity, any extraesophageal symptoms or quality of life scores, or inflammation on bronchoscopy or esophagogastroduodenoscopy (p>0.3). Conclusions Salivary pepsin measurement has a low sensitivity for predicting pathologic gastroesophageal reflux in children.

Background One of the primary reasons for referral for reflux testing is to correlate reflux events with symptoms such as cough. Adult studies have suggested that symptom recording is flawed and pediatricians feel this is an even more significant problem as there may be errors in both parental and patient report. We hypothesize that intraesophageal pressure recording (IEPR) provides an objective method to identify coughs during reflux testing in children. Methods We recruited 20 children undergoing pH-MII testing for the evaluation of cough. We placed simultaneous intraesophageal pressure and pH-MII catheters. Tracings were blindly scored by 2 observers without knowledge of patient/parent symptom report. After the blinded scoring, patient/parent report of symptoms was recorded. Results 94% of all coughs were detected by IEPR and only 48% of all coughs were reported by patients/parents. The mean time from the IEPR cough to the patient/parent cough was 11±16 seconds. Using IEPR as the gold standard for the detection of cough, the sensitivity of patient report for the detection of cough is 46%. Using varying symptom windows because of the increased precision of IEPR, the number of patients with a positive symptom index could be reduced from 30% down to 0%, preventing children from being falsely categorized as having reflux-related lung disease. Conclusions Parental and patient symptom recording in children is inadequate for making the diagnosis of reflux-related lung disease. If patients undergo pH-MII testing for reflux-related cough, IEPR should become the new standard by which to correlate reflux with cough.