Research Group "Lung Epidemiology" - Projects

PBMC: Proteasome Function as a Bio-Marker for COPD

Predictive biomarkers for stratification of COPD patients, deterioration and exacerbations of COPD are missing. The proteasome, a central enzymatic complex for degradation of intracellular proteins, is emerging as a new culprit in the pathogenesis and progression of COPD. The activity of this gatekeeper of protein homeostasis is impaired by cigarette smoke and in lung tissue of COPD patients. The effects of impaired proteasome function are twofold: On the one hand, impaired proteasome function affects protein homeostasis in the lung resulting in the accumulation of damaged proteins and thereby aggravating tissue damage. On the other hand, defective proteasome activity impairs MHC class I-mediated immune responses to viral and bacterial infections. Accordingly, proteasome dysfunction may contribute to onset and progression of COPD and in addition may result in increased susceptibility to infections and disease exacerbations in COPD patients.

We will profile expression and activity of the proteasome in peripheral blood cells of COPD patients of the COSYCONET cohort and model them in comparison to KORA-derived population data to validate proteasome function as a biomarker for COPD.

The specific objectives of this study are:

  • Characterise proteasome activity and expression as a function of COPD stages, COPD Assessment Test (CAT) scores, GOLD ABCD group and compare it to sex and age-matched healthy controls from the epidemiological cohort KORA FF4.

  • Determine to what extent comorbidities such as cardiovascular diseases, diabetes, obesity, and asthma, as well as physical performance (i.e. exercise capacity, daily physical activity), and restrictions in quality of life, modulate the association between proteasome activity and COPD.

  • Model proteasome function with COPD subtypes as determined by CT images. We will address how proteasome function correlates with the decline in lung function of COPD patients, development of COPD symptoms (CAT score), and the GOLD ABCD groups using a retrospective longitudinal approach.

We expect that our data will identify proteasomal activity and expression profiling as a feasible biomarker approach to stratify patients at high risk for progressive deterioration of COPD, comorbidities and higher exacerbation frequencies.

Study population:

COSYCONET: Screening a total of 450 COPD patients from COSYCONET: 150 with mild airflow limitation (GOLD I, FEV1 ≥80%), 150 with moderate (GOLD II), and 150 with severe airflow limitation (GOLD III-IV)

KORA: Comparison of these COPD patients with 300 sex and age-matched healthy controls from the epidemiological cohort KORA FF4.

Investigators:

Prof. Dr. med. Holger Schulz, Institute of Epidemiology, Helmholtz Zentrum München (Coordinating investigator),
Prof. Dr. rer. nat. Silke Meiners, Comprehensive Pneumology Center, Helmholtz Zentrum München
Prof. Dr. med. Claus Vogelmeier, UKGM Gießen-Marburg, Klinik für Innere Medizin, Schwerpunkt Pneumologie
Prof. Dr. med. Jürgen Behr, Medizinische Klinik und Poliklinik V, Klinikum der LMU

Funding: The German Center for Lung Research, DZL (01.2018 – 12.2020)

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