Development and Validation of test for Gastro-esophageal Reflux with Aspiration

描述（由申请人提供）：尽管在许多肺和气道疾病的发病和病程中怀疑反复微抽吸反流胃液（“微抽吸格尔”），但缺乏对其发生的无创、直接检测阻碍了对其重要性的研究。复杂的评估是它的夜间发生，当睡眠干扰保护反射。目前可用的测试，食管测压和24小时pH监测，或食道造影，是昂贵的，技术上困难和间接的，或涉及放射性物质。我们已经确定了两种化合物摄入后全身吸收不良;两者都被批准用于人类使用，副作用很少。一种是很好地从肺部和呼吸道吸收，并通过尿液排出。另一种不从肺和气道吸收，但可以制备成单分散不溶性颗粒。因此，我们建议检查第一种药物的过夜口服给药是否会导致更大的量， 10例复发性格尔患者的尿液中检测到的微抽吸比5例健康对照者的尿液中检测到的微抽吸要少。我们还建议在相同的受试者中检查第二种物质作为颗粒悬浮液给药是否导致在过夜收集的痰液中检测到不同的量，并在第二天早上诱导。我们将检验当两种药物同时给药时（第二种物质的颗粒悬浮在第一种物质的溶液中），结果的一致性。如果这项试点研究是有希望的，我们将提出第二阶段的研究，以完善的方法，并检查他们在更大数量的受试者。

DESCRIPTION (provided by applicant): Although recurrent microaspiration of refluxed gastric fluid ("GER with microaspiration") is suspected in the onset and course of many diseases of the lungs and airways, the lack of a non-invasive, direct test for its occurrence has hampered research on its importance. Complicating assessment is its nocturnal occurrence, when sleep interferes with protective reflexes. The tests currently available, esophageal manometry and 24h pH monitoring, or scintigraphy, are expensive, technically difficult and indirect, or involve radioactive material. We have identified two compounds poorly absorbed systemically after ingestion; both are approved for human use and have few side effects. One is well absorbed from the lungs and airways and excreted in urine. The other is not absorbed from the lungs and airways, but can be prepared in monodisperse insoluble particles. We accordingly propose to examine whether overnight oral administration of the first drug results in greater quantities being detected in urine from 10 patients thought to have recurrent GER with microaspiration than from 5 healthy controls. We also propose to examine in the same subjects whether administration of the second substance as a suspension of particles results in different quantities being detected in sputum collected overnight and induced the following morning. We will examine the concordance of the findings when the drugs are given together - the particles of the second substance suspended in a solution of the first. If this pilot study is promising, we will propose Phase II studies to refine the methods and examine them in larger numbers of subjects.