Rosen Rachel, Amirault Janine, Liu Hongye, Mitchell Paul, Hu Lan, Khatwa Umakanth, Onderdonk Andrew
Aerodigestive Center, Department of Gastroenterology, Boston Children's Hospital, Boston, Massachusetts.
Clinical Research Center, Boston Children's Hospital, Boston, Massachusetts.
JAMA Pediatr. 2014 Oct;168(10):932-7. doi: 10.1001/jamapediatrics.2014.696.
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.
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.
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.
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).
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.
在门诊环境中,使用抑酸药物与上、下呼吸道感染风险增加有关,但这种风险增加背后的机制尚不清楚。我们推测这种感染风险是由胃细菌过度生长并随后播散至肺部所致。
确定使用抑酸药物是否会导致胃细菌过度生长,使用抑酸药物是否会使肺部微生物群发生变化,以及肺部微生物群的变化是否与全柱无酸胃食管反流有关。
设计、地点和参与者:在一家三级医疗中心进行的一项为期5年的前瞻性队列研究,研究对象为1至18岁因慢性咳嗽接受支气管镜检查和内镜检查的儿童。通过问卷调查评估抑酸药物的使用情况,并通过电子病历审查进行确认。
我们的主要结局是比较接受和未接受抑酸治疗的患者之间胃和肺细菌浓度及患病率的差异。我们使用Wilcoxon符号秩检验比较中位数,并使用渐近标准误差和95%置信区间确定患病率比。我们使用Pearson相关系数确定连续变量之间的相关性,并使用Fisher精确检验比较分类变量。
服用抑酸药物的患者中有46%出现胃细菌生长,而未治疗患者中这一比例为18%(P = 0.003)。葡萄球菌(患病率比,12.75 [95% CI,1.72 - 94.36])、链球菌(患病率比,6.91 [95% CI,1.64 - 29.02])、韦荣球菌(患病率比,9.56 [95% CI,1.26 - 72.67])、皮肤杆菌(患病率比,4.78 [95% CI,1.09 - 21.02])和罗氏菌(患病率比,6.38 [95% CI,1.50 - 27.02])在接受治疗患者的胃液中更常见。接受治疗患者的细菌中位浓度高于未治疗患者(P = 0.001)。治疗组和未治疗组患者肺部不同细菌属的患病率(P > 0.23)或总细菌中位浓度(P = 0.85)无差异。近端无酸反流负担与肺部芽孢杆菌浓度(r = 0.47,P = 0.005)、皮肤杆菌浓度(r = 0.37,P = 0.008)、乳酸杆菌浓度(r = 0.45,P = 0.001)、消化链球菌浓度(r = 0.37,P = 0.008)和嗜二氧化碳噬纤维菌浓度(r = 0.37,P = 0.008)之间存在显著正相关。
使用抑酸药物会导致包括葡萄球菌和链球菌在内的细菌在胃中过度生长。全柱无酸反流与肺部细菌浓度升高有关。需要进一步研究以确定与抑酸相关的微生物群变化是否可预测临床感染风险;这些结果表明,对于有感染风险的患者,可能需要限制抑酸药物的使用。