SBIR-STTR Award

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.

Public Health Relevance Statement:


Public Health Relevance:
Microaspiration of gastric fluid into the respiratory tract (GER with aspirations) is suspected to be the cause of multiple severe respiratory diseases, yet there is no simple non-invasive method for routine clinical practice to detect this problem and investigate the results of interventions to stop it. We are developing a simple method based on ingestion of an oral liquid preparation containing two safe non-radioactive markers administered at night followed by urine and sputum collection to detect the markers of aspiration. If we find a significant difference between patients known to have GER with aspirations and healthy subjects with either of the two markers, we plan to make this diagnostic method commercially available for routine clinical practice.

Project Terms:
Adverse effects; Alcohol or Other Drugs use; analytical tool; aqueous; base; Biological Assay; chemical stability; clinical practice; Clinical Research; Collection; commercial application; Cromoglicic Acid; Cromolyn Sodium; Cystic Fibrosis; Detection; Development; Diagnostic Procedure; Diagnostic tests; Doctor of Philosophy; Dose; Esophageal; Evaluation; Fluorescein; Future; Gastroesophageal reflux disease; Government; Hamman-Rich syndrome; Hospitals; Hour; Human; Ingestion; Intervention; Intestines; Laboratories; Legal patent; Liquid substance; Literature; Lung; Lung diseases; Lung Transplantation; Manometry; Measures; Methods; Monitor; Oral; Oral Administration; Oropharyngeal; particle; Patients; Persons; Pharmaceutical Preparations; Phase; phase 2 study; Pilot Projects; Preparation; Process; public health relevance; Quality Control; Radioactive; Radionuclide Imaging; Recovery; Recurrence; Reflex action; Reflux; Reporting; Research; Respiratory System; Respiratory tract structure; Saliva; Sampling; Secondary to; Sedimentation process; Simulate; Sleep; Solutions; Sphincter; Sputum; Stomach; Suspension substance; Suspensions; Testing; tool; trend; Urine; Validation; Waxes; young adult