Putative Biomarkers for Acute Pulmonary Embolism in Exhaled Breath Condensate.

Inger Lise Gade,Asger Andersen,Rasmus Froberg Brøndum,Jacob Gammelgaard Schultz,Benedict Kjærgaard,Bent Honoré,Søren Risom Kristensen,Jens Erik Nielsen-Kudsk

doi:10.3390/jcm10215165

Abstract

Current diagnostic markers for pulmonary embolism (PE) are unspecific. We investigated the proteome of the exhaled breath condensate (EBC) in a porcine model of acute PE in order to identify putative diagnostic markers for PE. EBC was collected at baseline and after the induction of autologous intermediate-risk PE in 14 pigs, plus four negative control pigs. The protein profiles of the EBC were analyzed using label-free quantitative nano liquid chromatography–tandem mass spectrometry. A total of 897 proteins were identified in the EBCs from the pigs. Alterations were found in the levels of 145 different proteins after PE compared with the baseline and negative controls: albumin was among the most upregulated proteins, with 14-fold higher levels 2.5 h after PE (p-value: 0.02). The levels of 49 other proteins were between 1.3- and 17.1-fold higher after PE. The levels of 95 proteins were lower after PE. Neutrophil gelatinase-associated lipocalin (fold change 0.3, p-value < 0.01) was among the most reduced proteins 2.5 h after PE. A prediction model based on penalized regression identified five proteins including albumin and neutrophil gelatinase-associated lipocalin. The model was capable of discriminating baseline samples from EBC samples collected 2.5 h after PE correctly in 22 out of 27 samples. In conclusion, the EBC from pigs with acute PE contained several putative diagnostic markers of PE.

Highlights

The diagnostic workup for pulmonary embolism (PE) includes clinical examination evaluating the clinical probability of PE, D-dimer testing, and imaging diagnostics [1].neither the clinical presentation nor the initial tests are specific for PE [2,3].there is an unmet need for diagnostic biomarkers to enhance the early and precise diagnosis of PE.The air we exhale contains water vapor, volatile organic compounds and low concentrations of proteins; these concentrations are still high enough for mass spectrometry analysis
In a recent pilot study based on seven pigs with PE, we identified 131 proteins in the exhaled breath condensate (EBC) [9], and 79 of these proteins were identified by mass spectrometry in a human study using the same EBC collection
Med. 2021, 10, 5165 based on seven pigs with PE, we identified 131 proteins in the EBC [9], and 79 of these proteins were identified by mass spectrometry in a human study using the same EBC

Summary

Introduction

The diagnostic workup for pulmonary embolism (PE) includes clinical examination evaluating the clinical probability of PE, D-dimer testing, and imaging diagnostics [1].neither the clinical presentation nor the initial tests are specific for PE [2,3].there is an unmet need for diagnostic biomarkers to enhance the early and precise diagnosis of PE.The air we exhale contains water vapor, volatile organic compounds and low concentrations of proteins; these concentrations are still high enough for mass spectrometry analysis. The diagnostic workup for pulmonary embolism (PE) includes clinical examination evaluating the clinical probability of PE, D-dimer testing, and imaging diagnostics [1]. Neither the clinical presentation nor the initial tests are specific for PE [2,3]. The air we exhale contains water vapor, volatile organic compounds and low concentrations of proteins; these concentrations are still high enough for mass spectrometry analysis. This biological specimen, called exhaled breath condensate (EBC), can be collected non-invasively in both conscious and intubated individuals [4]. In a recent pilot study based on seven pigs with PE, we identified 131 proteins in the EBC [9], and 79 of these proteins were identified by mass spectrometry in a human study using the same EBC collection

Methods

Results

Discussion

Conclusion