More than 12% of children are diagnosed with asthma over the course of their childhood and up to 73% of children with asthma have evidence of pathologic reflux by pH testing. This study will determine the role of microaspiration of refluxed contents in the genesis of asthma and cough. We will recruit children ages 1 to 21 years who are undergoing bronchoscopy, endoscopy, and multichannel intraluminal impedance testing (pH-MII) for the evaluation of asthma and cough. Using bronchial lavage and gastric fluid, we will determine: (1) if full column reflux results in aspiration of gastric contents into the lung;(2) if aspiration of gastric contents results in lung inflammation;and (3) if the bacterial composition in the lungs mimics the bacterial composition in gastric fluid in children with reflux-related pulmonary disease. First, we will determine the frequency of bile in the lungs of patients with pulmonary disease. Bile should only present in the gastrointestinal tract so its presence in the lungs would indicate microaspiration. We will compare the amount of full column gastroesophageal reflux, measured pH-MII, in those patients with and without bile in the lungs to determine if full column reflux is an indicator of reflux-related lung disease. Second, we will determine if patients with bile in the lung have higher NF-(B activation and different cytokine patterns than patients without bile in the lung. Bile provokes an inflammatory response in esophageal tissue and we hypothesize that bile in the lung will result in a similar inflammatory response. Third, we will determine the proportion of patients in whom there are matching bacterial species between the gastric and lung fluid;we hypothesize that bacteria inhabit the stomach and that these bacteria can be refluxed and aspirated resulting in matching species of bacteria between gastric and lung fluid. Additionally, we anticipate that, in patients with matching bacterial species, there will be higher levels of NF-(B activity and different cytokine patterns than those patients without matching species. The results of this study will be used to determine more accurately which patients have reflux-related lung disease and, therefore, could benefit from reflux therapy.

Public Health Relevance

This study will determine the role of microaspiration in the genesis of asthma and cough through the measurement of new markers of reflux-related lung disease including bile and bacterial composition. The results of the study will allow clinicians to better determine which patients with respiratory disease will benefit from reflux therapy.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Small Research Grants (R03)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Podskalny, Judith M,
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Children's Hospital Boston
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Rosen, Rachel; Hu, Lan; Amirault, Janine et al. (2015) 16S community profiling identifies proton pump inhibitor related differences in gastric, lung, and oropharyngeal microflora. J Pediatr 166:917-23
Rosen, Rachel; Amirault, Janine; Giligan, Emily et al. (2014) Intraesophageal pressure recording improves the detection of cough during multichannel intraluminal impedance testing in children. J Pediatr Gastroenterol Nutr 58:22-6
Rosen, Rachel; Amirault, Janine; Johnston, Nikki et al. (2014) The utility of endoscopy and multichannel intraluminal impedance testing in children with cough and wheezing. Pediatr Pulmonol 49:1090-6
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