Microaspiration as a cause for respiratory disease in children

微吸入是儿童呼吸道疾病的一个原因

• 批准号: 8080216
• 负责人: Rachel L Rosen
• 金额: $ 8.59万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8080216
• 关键词: Address; Age; Aspirate substance; Asthma; Bacteria; Bile Acids; Bile fluid; Biological Assay; Boston; Bronchial Lavages; Bronchoscopy; Child; Childhood; Chronic; Commit; Coughing; Data; Diagnosis; Diagnostic; Disease; Distal; Endoscopy; Endotoxins; Esophageal Tissue; Esophagus; Evaluation; Frequencies; Gastroesophageal reflux disease; Gastrointestinal tract structure; Goals; Gold; Inflammatory; Inflammatory Response; Liquid substance; Lung; Lung Inflammation; Lung diseases; Measurement; Measures; Mentors; Microbe; Monitor; Morbidity - disease rate; Pathologic; Patients; Pattern; Pediatric Hospitals; Pepsin A; Pneumonia; Principal Investigator; Pulmonary aspiration of gastric contents; Recruitment Activity; Reflux; Research Infrastructure; Research Personnel; Role; Stomach; Testing; Time; cytokine; electric impedance; hypopharynx; insight; novel marker; public health relevance; tool

DESCRIPTION (provided by applicant): 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.

描述(由申请人提供)： 超过12%的儿童在童年期间被诊断为哮喘，多达73%的哮喘儿童通过pH检测有病理性反流的证据。本研究将确定微量吸入返流内容物在哮喘和咳嗽发生中的作用。我们将招募1至21岁接受支气管镜检查、内窥镜检查和多通道管腔内阻抗测试(pH-MII)以评估哮喘和咳嗽的儿童。使用支气管灌洗和胃液，我们将确定：(1)全柱回流是否会导致胃内容物吸入肺部；(2)是否吸入胃内容物会导致肺部炎症；以及(3)肺部的细菌组成是否与反流相关肺部疾病儿童胃液中的细菌组成相似。 首先，我们将确定肺部疾病患者肺部胆汁的频率。胆汁应该只存在于胃肠道中，所以它在肺部的存在表明有微小的吸入物。我们将比较肺部有胆汁和无胆汁的患者的全柱式胃食道反流量，测量的pH-MII，以确定全柱式反流是否是反流相关肺部疾病的指标。 其次，我们将确定有肺胆汁的患者是否比无胆汁的患者有更高的NF-B活性和不同的细胞因子模式。胆汁会在食道组织中引发炎症反应，我们假设肺中的胆汁也会导致类似的炎症反应。 第三，我们将确定胃液和肺液中有匹配细菌种类的患者的比例；我们假设细菌居住在胃中，这些细菌可以回流和吸入，从而产生胃液和肺液中匹配的细菌种类。此外，我们预计，在细菌种类匹配的患者中，与那些没有匹配细菌种类的患者相比，将会有更高水平的核因子-B活性和不同的细胞因子模式。 这项研究的结果将被用来更准确地确定哪些患者患有反流相关的肺部疾病，因此可以从反流治疗中受益。 公共卫生相关性： 这项研究将通过测量反流相关肺部疾病的新标记物，包括胆汁和细菌成分，来确定微量吸入物在哮喘和咳嗽发生中的作用。这项研究的结果将使临床医生能够更好地确定哪些呼吸系统疾病患者将从反流治疗中受益。