A breath-based in vitro diagnostic assay for the detection of lower respiratory tract infections
An accurate diagnosis is critical to reducing mortality in people with lower respiratory tract infections (LRTIs). Current microbiological culture is time-consuming, and nucleic acid amplification-based molecular technologies cannot distinguish between colonization and infection. Previously, we desc...
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Published in | PNAS nexus Vol. 3; no. 9; p. pgae350 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
24.09.2024
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Subjects | |
Online Access | Get full text |
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Summary: | An accurate diagnosis is critical to reducing mortality in people with lower respiratory tract infections (LRTIs). Current microbiological culture is time-consuming, and nucleic acid amplification-based molecular technologies cannot distinguish between colonization and infection. Previously, we described developing a sampling system for effectively capturing biomolecules from human breath. We identified a new class of proteoform markers of protease activation, termed proteolytic products of infection, for detecting LRTIs in people with mechanical ventilation. Here, we further developed an in vitro assay by designing a specific substrate sensor for human neutrophil elastase (HNE) to detect LRTIs in breath samples. In the proof-of-concept study, we then applied this in vitro assay to breath samples collected from intubated patients and healthy volunteers. The findings revealed that the LRTI group demonstrated a significant mean differential, showing a 9.8-fold elevation in measured HNE activity compared with the non-LRTI group and a 9.2-fold compared with healthy volunteers. The in vitro assay's diagnostic potential was assessed by constructing a receiver operating characteristic curve, resulting in an area under the curve of 0.987. Using an optimal threshold for HNE at 0.2 pM, the sensitivity was determined to be 1.0 and the specificity to be 0.867. Further correlation analysis revealed a strong positive relationship between the measured HNE activity and the protein concentration in the breath samples. Our results demonstrate that this breath-based in vitro assay provides high diagnostic performance for LRTIs, suggesting that the technology may be useful in the near term for the accurate diagnosis of LRTIs. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interest: D.C., K.M.K, C.R.H., E.R.C., M.S.C., W.A.B., and M.M. have competing interests. D.C., K.M.K., C.R.H., M.S.C., and E.R.C. are employed by Zeteo Tech, Inc. W.A.B. and M.M. serve as chief executive officer and chief technology officer for Zeteo Tech, Inc., respectively. M.A.M., Y.P., and S.C. have no competing interests. An unpublished US Provisional Patent Application assigned to Zeteo Tech, Inc. was applied based on this research. |
ISSN: | 2752-6542 2752-6542 |
DOI: | 10.1093/pnasnexus/pgae350 |