A Breath-Based In Vitro Diagnostics for Lower Respiratory Tract Infection


Lower Respiratory Tract Infections (LRTIs) represent the leading cause of death due to infectious diseases. Current diagnostic modalities primarily depend on clinical symptoms and lack specificity, especially in light of common colonization without overt infection. To address this, we developed a noninvasive diagnostic approach that employs BreathBiomicsTM, an advanced human breath sampling system, to detect protease activities induced by bacterial infection in the lower respiratory tract. Specifically, we engineered a high-sensitivity and high-specificity molecular sensor for human neutrophil elastase (HNE). The sensor undergoes cleavage in the presence of HNE, an event that is subsequently detected via Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). Application of this methodology to clinical samples, breath specimens collected from intubated patients with LRTIs, demonstrated the detection of the cleaved sensor by MALDI-TOF MS. Our findings indicate that this novel approach offers a noninvasive and specific diagnostic strategy for people with LRTIs.

Competing Interest Statement

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. and S.C. have no competing interests. An unpublished U.S. Provisional Patent Application assigned to Zeteo Tech, Inc. was applied based on this research.

Funding Statement

This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the NIH under Awards R44AI177245.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.


The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study received approval from the Institutional Review Boards at The Johns Hopkins University School of Medicine (Application Number: IRB00249449), and all study participants provided informed consent. All experimental procedures were executed in accordance with these approved protocols.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.


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Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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