PNNL

Abstract

Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at San Antonio Military Medical Center. The evaluation included fiberoptic bronchoscopy with brochoalveolar lavage. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine or lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins and miRNAs associated with the general diagnosis of dyspnea have been identified. Since these markers can be measured in readily obtained clinical samples, further studies are possible that test their value in case-control studies of specific lung diseases such as asthma or emphysema as well as disease progression.