Item type:Doctoral Thesis, Open Access

Differenzialdiagnostisches Potenzial von RNA-Biomarkern bei CAP, CAP bei COPD und AECOPD, sowie Einschätzung des Schweregrades der ambulant erworbenen Pneumonie

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Abstract

Acute respiratory infections are among the most common infectious diseases worldwide and account for a large proportion of hospital admissions in Germany. In patients with COPD, whose prevalence in Germany ranges between 2% and 16% depending on age group, acute respiratory infections often lead to exacerbation or CAP. Distinguishing between CAP, AECOPD and CC is difficult with current diagnostic tools, but is of considerable therapeutic and prognostic relevance. In this exploratory study, seven mRNAs (hsa_circ_0026579, GADD45A, BPGM, DYRK2, TAP2, CCNB1IP1 and IFIT5) were investigated for their potential as biomarkers for differentiating between the stated disease entities. In addition, it was examined whether they allow conclusions to be drawn about the severity of CAP. In addition to the mRNA profiles, blood counts, CRP, clinical data and established scores (PSI, CURB, CRB65, GOLD I–IV, GOLD ABCD) were recorded. A total of 109 individuals were included in the analysis, whose characteristics are comparable to larger national cohorts. The analysis of the RNA profiles enabled a more precise classification of the disease entities and an improved assessment of the severity of CAP. The validity of hsa_circ_0026579 as a biomarker for CAP, as previously described by Zhao et al., was confirmed. In addition, GADD45A was identified as a potential new biomarker. A direct link to respiratory tract infections was unknown until now, but GADD45A is described as a stress and repair gene, which suggests a protective function in lung injury. There was no diagnostic potential for the severity grading. DYRK2 showed significant differences from the healthy control group in all disease groups. The strongest distinction was between AECOPD and healthy individuals. In addition, there were indications of a possible suitability for assessing CAP severity. DYRK2 is involved in the regulation of inflammatory and apoptotic processes, although the specific mechanisms in the context of CAP or AECOPD have not yet been conclusively clarified. Only BPGM enabled the identification of a milder form of CAP. Increased expression could modulate an excessive immune response by influencing glycolysis and serine biosynthesis, thus contributing to a milder clinical course. In the literature to date, elevated BPGM has mainly been described in the context of sepsis. The RNAs examined showed potential for identifying patients with respiratory infections. However, compared to established inflammatory markers, the additional diagnostic benefit was limited. It was not possible to reliably differentiate between the disease entities on the basis of the markers. Further transcriptome analyses are necessary to identify reliable biomarkers for diagnostic differentiation. DYRK2 and BPGM appear particularly promising for assessing the severity of CAP. Their validation in larger, multicenter studies is necessary to confirm their clinical utility and enable a more accurate classification of severity in the future.

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Veeger, Pia-Marie: Differenzialdiagnostisches Potenzial von RNA-Biomarkern bei CAP, CAP bei COPD und AECOPD, sowie Einschätzung des Schweregrades der ambulant erworbenen Pneumonie. : 2026-02-27.

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