A mRNA panel for differentiation between acute exacerbation or pneumonia in COPD patients

Front Med (Lausanne). 2024 Mar 22:11:1234068. doi: 10.3389/fmed.2024.1234068. eCollection 2024.

Abstract

Introduction: Patients suffering from chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations (AECOPD) or community acquired pneumonia (CAP), both posing severe risk of morbidity and mortality. There is no available biomarker that correctly separates AECOPD from COPD. However, because CAP and AECOPD differ in aetiology, treatment and prognosis, their discrimination would be important.

Methods: This study analysed the ability of selected candidate transcripts from peripheral blood mononuclear cells (PBMCs) to differentiate between patients with AECOPD, COPD & CAP, and CAP without pre-existing COPD.

Results: In a previous study, we identified differentially regulated genes between CAP and AECOPD in PBMCs. In the present new cohort, we tested the potential of selected candidate PBMC transcripts to differentiate at early time points AECOPD, CAP+COPD, and CAP without pre-existing COPD. Expression of YWHAG, E2F1 and TDRD9 held predictive power: This gene set predicted diseases markedly better (model accuracy up to 100%) than classical clinical markers like CRP, lymphocyte count and neutrophil count (model accuracy up to 82%).

Discussion: In summary, in our cohort expression levels of YWHAG, E2F1 and TDRD9 differentiated with high accuracy between COPD patients suffering from acute exacerbation or CAP.

Keywords: COPD; COPD exacerbation; comorbidity; pneumonia; transcriptome.

Grants and funding

This work has been funded in part by the Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research: PermedCOPD – FKZ 01EK2203A; ERACoSysMed2 – SysMed-COPD – FKZ 031 L0140; e:Med CAPSYS – FKZ 01ZX1604E), the Deutsche Forschungsgemeinschaft (SFB/TR-84 TP C01), and the von-Behring-Röntgen-Stiftung (66-LV07) to BS, as well as the Hessisches Ministerium für Wissenschaft und Kunst (LOEWE Diffusible Signals LOEWE-Schwerpunkt Diffusible Signals) to BS. Open Access funding provided by the Open Acess Publishing Fund of Philipps-Universität Marburg.