Publication Date

2020

Document Type

Thesis

Committee Members

David R. Cool, Ph.D. (Advisor); Ravi P. Sahu, Ph.D. (Committee Member); Jeffery B. Travers, M.D., Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Ventilator associated pneumonia (VAP) is the most common nosocomial infection leading to increased mortality in ICU patients. The main goal of this project was to evaluate and analyze a number of different biomarkers of disease that may be involved in the transition to pneumonia in patients on ventilators. Patients in this study were in the ICU, required greater than or equal to 48 hours of mechanical ventilation, and had a Clinical Pulmonary Infection Score greater than or equal to 6. For this study we recruited 16 subjects who were on ventilator for more than 48 hours, obtained serum and sputum from each that was frozen at -80°C and stored until use. Six patients developed pneumonia (VAP) and the rest were considered Non-VAP. Our goal was to analyze cytokine levels, Platelet-activating factor acteylhydrolase (PAFAh), procalcitonin, vitamin D, and pentraxins, in the sputum as well as serum samples from these patients. PAFAh is an enzyme that inactivates platelet activating factor, which is involved in cytokine release. Pentraxin3 is an early marker of lung injury. Using the Bio-Rad BioPlex system, we analyzed 27 cytokines in sputum and serum. Of these, we found that 6 were significantly increased in the sputum of VAP patients, while only 1 was significantly increased in the serum from VAP patients. The PAFAh assay revealed no significant difference between VAP and non-VAP patient sputum or serum, though there was a trend for lower PAFAh in VAP patients compared to non-VAP. Analysis for Pentraxin3 indicated that it was present in both sputum and serum though there was no significant difference. Sequencing of fragmented peptides from the sputum also revealed a peptide from pneumonia bacteria. In conclusion, the results strongly suggest that a larger study is needed, in addition to cytokines, other enzymes and proteins need to be explored as potential markers for early diagnosis and potential new treatments of VAP.

Page Count

88

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2020

ORCID ID

0000-0003-1889-6805


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