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Title: Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. 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 forty-eight dyspnea subjects compared to fifteen controls with no knownmore » lung disorder. Six of these proteins were detected both in urine and 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 in subjects with differing medical diagnoses. Since these markers can be measured in readily obtained clinical samples, further studies are possible that test the value of these findings in more formal classification or case–control studies in much larger cohorts of subjects with specific lung diseases such as asthma, emphysema, or some other well-defined lung disease.« less
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [1] ;  [1] ;  [3] ;  [3]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. San Antonio Military Medical Center, San Antonio, TX (United States)
  3. Institute for Systems Biology, Seattle, WA (United States)
Publication Date:
OSTI Identifier:
1209001
Grant/Contract Number:
AC05-76RL01830
Type:
Accepted Manuscript
Journal Name:
BMC Medical Genomics
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 1755-8794
Publisher:
BioMed Central
Research Org:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE dyspnea; biomarkers; lavage fluid; serum; urine; proteomics; MicroRNAs