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

描述（由申请人提供）：虽然反复微吸反流胃液（“微吸GER”）在许多肺部和呼吸道疾病的发病和病程中被怀疑，但缺乏对其发生的非侵入性直接测试，阻碍了对其重要性的研究。更复杂的评估是夜间发生，当睡眠干扰保护性反射时。目前可用的检测方法是食道测压和24小时pH监测或闪烁成像，这些方法昂贵、技术困难且间接，或涉及放射性物质。我们已经确定了两种化合物在摄入后系统吸收不良；这两种药物都被批准用于人体，而且几乎没有副作用。一种可以很好地从肺部和呼吸道吸收，并随尿液排出。另一种不能从肺部和呼吸道吸收，但可以制备成单分散的不溶性颗粒。因此，我们建议检查夜间口服第一种药物是否会导致更大的剂量

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.