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Original Investigation |

Changes in Gastric and Lung Microflora With Acid Suppression:  Acid Suppression and Bacterial Growth ONLINE FIRST

Rachel Rosen, MD, MPH1; Janine Amirault, BA1; Hongye Liu, PhD2; Paul Mitchell, MS2; Lan Hu, PhD3; Umakanth Khatwa, MD4; Andrew Onderdonk, PhD5
[+] Author Affiliations
1Aerodigestive Center, Department of Gastroenterology, Boston Children’s Hospital, Boston, Massachusetts
2Clinical Research Center, Boston Children’s Hospital, Boston, Massachusetts
3Center for Computational Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts
4Aerodigestive Center, Department of Pulmonary Medicine, Boston Children’s Hospital, Boston, Massachusetts
5Department of Microbiology, Brigham and Women’s Hospital, Boston, Massachusetts
JAMA Pediatr. Published online August 18, 2014. doi:10.1001/jamapediatrics.2014.696
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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.

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Figure 1.
Difference in Total Median Concentrations

A, Patients receiving and not receiving acid-suppression therapy in gastric samples. B, Patients receiving and not receiving acid-suppression therapy in lung samples. IQR indicates interquartile range.

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Figure 2.
Differences in Bacterial Prevalence Ratios

A, Patients receiving and not receiving acid-suppression therapy in the gastric flora. B, Patients receiving and not receiving acid-suppression therapy in the lung flora. Genera with prevalence ratios to the right of 1 are more common in patients taking acid-suppression therapy while genera to the left of 1 are more common in patients not receiving therapy.

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