Janine Amirault

Changes in Gastric and Lung Microflora With Acid Suppression Acid Suppression and Bacterial Growth

IMPORTANCE 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 PARTICIPANTS A 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 MEASURES Our 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 (r = 0.47, P = .005), Dermabacter (r = 0.37, P = .008), Lactobacillus (r = 0.45, P = .001), Peptostreptococcus (r = 0.37, P = .008), and Capnocytophagia (r = 0.37, P = .008). CONCLUSIONS AND RELEVANCE Acid-suppression use results in gastric bacterial overgrowth of genera including Staphylococcus and Streptococcus. Full-column nonacid reflux is associated with greater concentrations of bacteria in the lung. Additional studies are needed to determine if acid suppression-related microflora changes predict clinical infection risk; these results suggest that acid suppression use may need to be limited in patients at risk for infections.

16S community profiling identifies proton pump inhibitor related differences in gastric, lung and oropharyngeal microflora

OBJECTIVES To test the hypothesis that proton pump inhibitor (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 testing. RESULTS Streptococcus was more abundant in the gastric fluid of patients taking PPIs, and there was a significant correlation with PPI dose (mg/kg/d) and abundance of gastric Streptococcus (P = .01). There was also a significant difference in the abundance of oropharyngeal Streptococcus in patients treated with PPI. Eight unique bacterial genera were found in the gastric and lung fluid but not in the oropharyngeal suggesting exchange between the 2 sites and 2 of the 8 (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 3 sites, gastric and lung microflora are more closely related, and the mechanism of exchange between sites may be aspiration of full column reflux.

The utility of endoscopy and multichannel intraluminal impedance testing in children with cough and wheezing

Gastroesophageal reflux (GER) has been implicated as a causal factor in respiratory disease but prior studies have focused on the role of acid alone in the genesis of symptoms. Prior studies have relied on pH probe testing but this is blind to non‐acid reflux which has been implicated in the genesis of extraesophageal symptoms. The objective of this prospective, cross‐sectional study is to determine the utility of gastroesophageal reflux testing, including multichannel intraluminal impedance with pH (pH‐MII) and upper gastrointestinal endoscopy (EGD), in the child with intractable cough and wheezing. We hypothesize that there is a high rate of pathologic reflux testing in these patients.

Intraesophageal pressure recording improves the detection of cough during multichannel intraluminal impedance testing 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 because there may be errors in both parental and patient reports. 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 multichannel intraluminal impedance with pH (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: Ninety-four percent 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 criterion 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% 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.

Salivary Pepsin Lacks Sensitivity as a Diagnostic Tool to Evaluate Extraesophageal Reflux Disease

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 Childrens Hospital who were undergoing pH-MII to evaluate for GERD. The patients completed 24-hour pH-MII testing, completed symptom and quality of life questionnaires, and provided a saliva specimen that was analyzed using the PepTest lateral flow test. A subset of patients also underwent bronchoscopy and esophagogastroduodenoscopy. Receiver operating characteristic curve analyses were performed to determine the sensitivity of salivary pepsin compared with each reference standard. RESULTS Twenty-one of the 50 patients (42%) were salivary pepsin-positive, with a median salivary pepsin concentration of 10 ng/mL (IQR, 10-55 ng/mL). There was no significant difference in the distributions of acid, nonacid, total reflux episodes, full column reflux, or any other reflux variable in patients who were pepsin-positive compared with those who were pepsin-negative (P > .50). There was no significant correlation between the number of reflux episodes and pepsin concentration (P > .10). There was no positive relationship between salivary pepsin positivity, any extraesophageal symptoms or quality of life scores, or inflammation on bronchoscopy or esophagogastroduodenoscopy (P > .30). CONCLUSION Salivary pepsin measurement has a low sensitivity for predicting pathological gastroesophageal reflux in children.

The sensitivity of acoustic cough recording relative to intraesophageal pressure recording and patient report during reflux testing

One of the primary indications for reflux testing with multichannel intraluminal impedance with pH (pH‐MII) is to correlate reflux events with symptoms such as cough. Adult and pediatric studies have shown, using cough as a model, that patient report of symptoms is inaccurate. Unfortunately, intraesophageal pressure recording (IEPR) to record coughs is more invasive which limits its utility in children. The primary aim of this study was to validate the use of acoustic cough recording (ACR) during pH‐MII testing.

Oropharyngeal Dysphagia is Strongly Correlated With Apparent Life-Threatening Events.

Objectives: The aim of the present study was to investigate the prevalence of oropharyngeal dysfunction with resultant aspiration in patients admitted after apparent life-threatening events (ALTE) and to determine whether historical characteristics could predict this oropharyngeal dysphagia and aspiration risk. Methods: We retrospectively reviewed the records of all patients admitted to Boston Childrens Hospital between 2012 and 2015 with a diagnosis of ALTE to determine the frequency of evaluation for oropharyngeal dysphagia using video fluoroscopic swallow studies (VFSS) and clinical feeding evaluations, to determine the prevalence of swallowing dysfunction in subjects admitted after ALTE and to compare presenting historical characteristics to swallow study results. Results: A total of 188 children were admitted with a diagnosis of ALTE of which 29% (n = 55) had an assessment of swallowing by VFSS. Of those who had a VFSS, 73% (n = 40) had evidence of aspiration or penetration on VFSS. Of all of the diagnostic tests ordered on patients with ALTEs, the VFSS had the highest rate of abnormalities of any test ordered. None of the historical characteristics of ALTE predicted which patients were at risk for aspiration. In patients who had both clinical feeding evaluations and VFSS, observed clinical feedings incorrectly identified 26% of patients as having no oropharyngeal dysphagia when in fact aspiration was present on VFSS. Conclusions: Oropharyngeal dysphagia with aspiration is the most common diagnosis identified in infants presenting with ALTEs. The algorithm for ALTE should be revised to include an assessment of VFSS as clinical feeding evaluations are inadequate to assess for aspiration.

Gastroesophageal Reflux Burden, Even in Children That Aspirate, Does Not Increase Pediatric Hospitalization.

Objectives: Gastroesophageal reflux is common but remains a controversial disease to diagnose and treat and little is known about the role of reflux testing in predicting clinical outcomes, particularly in children at risk for extraesophageal reflux complications. The aim of this study was to determine if rates of hospitalization were affected by reflux burden even after adjusting for aspiration risk. Methods: We prospectively recruited, between 2009 and 2014, a cohort of pediatric patients with suspected extraesophageal reflux disease who were referred for reflux testing and underwent both multichannel intraluminal impedance with pH (pH-MII) and modified barium swallow studies. A subset of patients also underwent bronchoalveolar lavage with pepsin analysis. We determined their rates of hospitalization for a minimum of 1 year following pH-MII testing. Results: We prospectively enrolled 116 pediatric patients who presented for care at Boston Childrens Hospital and underwent both pH-MII and modified barium swallow studies. There was no statistically significant relationship between reflux burden measured by pH-MII or bronchoalveolar pepsin and total number of admissions or number of admission nights even after adjusting for aspiration status (P > 0.2). There were no statistically significant relationships between reflux burden by any method and the number or nights of urgent pulmonary admissions before or after adjusting for aspiration risk (P > 0.08). Conclusions: Even in aspirating children, reflux burden did not increase the risk of hospitalization. Based on these results, routine reflux testing cannot be recommended even in aspirating children, because the results do not impact clinically significant outcomes.

Su1157 Antibiotic Use Increases the Abundance of Potential Pathogenic Gastric Bacteria in Children Taking Proton Pump Inhibitors

polymorphism and widely used in the eradication, rabeprazole (RPZ) and esomeprazole (EPZ). Patients and methods: This was a prospective, multi-centered, non-blinded, randomized clinical trial. We conducted tests such as rapid urease test or urea breath test (UBT) in patients confirmed of having gastric/duodenal ulcers or chronic atrophic gastritis by esophagogastroduodenoscopy (EGD) to find the infection status of H. pylori, and 147 positive patients were enrolled. Gastric juice was collected to see the CYP2C19 polymorphism and CAM resistant rate during EGD. Patients were randomized into either RPZ 10 mg bid + AMPC 750 mg bid + CAM 200 mg bid for 7 days group or EPZ 20 mg bid + AMPC 750 mg bid + CAM 200 mg bid for 7 days group. Background factors (age, gender, height, weight, BMI, smoking, alcohol, concomitant drugs, baseline disease) were studied, and eradication was evaluated by UBT at least four weeks after the end of the eradication therapy. Results: The evaluation subject was 147 patients, and a background factors did not have the significant difference between both groups (p>0.05). The eradication rate in RPZ group was 68.4% (52/76) while it of EPZ group was 77.5% (55/71), with no significant difference between groups (p=0.27). Overall CAM resistant rate 15% (22/147). As for the eradication success rate of CAM resistant, the eradication rate in RPZ group was 40.0% (2/5) while it of EPZ group was 52.9% (9/17), with no significant difference between groups (p>0.05). In all, the ratio distribution of CYP2C19 genotype was RM 31%(19/61), intermediate metabolizers (IM) 54 %( 33/61), poor metabolizers (PM) 15%(9/61). Between the two groups, there was no significant difference in the success rate of eradication by each genotype (p>0.05). Conclusions: In the eradication rate of H. pylori by the triple therapy, RPZ and EPZ were comparable. Also, in the examination by clarithromycin resistance and CYP2C19 genotype, the eradication rate of both drugs was equivalent.

Su1158 Sensitivity and Specificity of Salivary Pepsin Compared to Multichannel Intraluminal Impedance and pH-Metry in Children With Respiratory Symptoms

polymorphism and widely used in the eradication, rabeprazole (RPZ) and esomeprazole (EPZ). Patients and methods: This was a prospective, multi-centered, non-blinded, randomized clinical trial. We conducted tests such as rapid urease test or urea breath test (UBT) in patients confirmed of having gastric/duodenal ulcers or chronic atrophic gastritis by esophagogastroduodenoscopy (EGD) to find the infection status of H. pylori, and 147 positive patients were enrolled. Gastric juice was collected to see the CYP2C19 polymorphism and CAM resistant rate during EGD. Patients were randomized into either RPZ 10 mg bid + AMPC 750 mg bid + CAM 200 mg bid for 7 days group or EPZ 20 mg bid + AMPC 750 mg bid + CAM 200 mg bid for 7 days group. Background factors (age, gender, height, weight, BMI, smoking, alcohol, concomitant drugs, baseline disease) were studied, and eradication was evaluated by UBT at least four weeks after the end of the eradication therapy. Results: The evaluation subject was 147 patients, and a background factors did not have the significant difference between both groups (p>0.05). The eradication rate in RPZ group was 68.4% (52/76) while it of EPZ group was 77.5% (55/71), with no significant difference between groups (p=0.27). Overall CAM resistant rate 15% (22/147). As for the eradication success rate of CAM resistant, the eradication rate in RPZ group was 40.0% (2/5) while it of EPZ group was 52.9% (9/17), with no significant difference between groups (p>0.05). In all, the ratio distribution of CYP2C19 genotype was RM 31%(19/61), intermediate metabolizers (IM) 54 %( 33/61), poor metabolizers (PM) 15%(9/61). Between the two groups, there was no significant difference in the success rate of eradication by each genotype (p>0.05). Conclusions: In the eradication rate of H. pylori by the triple therapy, RPZ and EPZ were comparable. Also, in the examination by clarithromycin resistance and CYP2C19 genotype, the eradication rate of both drugs was equivalent.