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

描述(申请人提供)：尽管反流胃液反复微抽吸(“GER伴微抽吸”)被怀疑是许多肺部和呼吸道疾病的发病和病程，但缺乏对其发生的非侵入性、直接检测，阻碍了对其重要性的研究。更复杂的评估是它在夜间发生，当睡眠干扰保护性反射时。目前可用的检查，如食道测压和24小时酸碱度监测，或核素扫描，价格昂贵，技术困难，而且是间接的，或者涉及放射性物质。我们已经确定了两种摄取后全身吸收不良的化合物；这两种化合物都被批准用于人类，而且几乎没有副作用。其中一种从肺部和呼吸道被很好地吸收，并通过尿液排泄。另一种是不能从肺部和呼吸道吸收的，但可以制备成单分散的不溶性颗粒。因此，我们建议研究通宵口服第一种药物是否会导致更多的 从10名被认为是复发的GER患者的尿液中检测到微量吸入物，而不是从5名健康对照中检测到。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剂的给药是否会导致在夜间收集的痰和第二天早上诱导的痰中检测到不同的量。当两种药物一起服用时，我们将检查结果的一致性--第二种物质的颗粒悬浮在第一种物质的溶液中。如果这项初步研究有希望，我们将提出第二阶段研究，以改进方法，并在更多的对象中进行检查。

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.