COPD – when the air makes you sick
Smoking, airborne pollutants, microorganisms – these and other causes mean that the entire medical community is increasingly having to deal with COPD. Chronic obstructive pulmonary disease (COPD) can already be described as a widespread disease, colloquially referred to as "smoker's lung". It is estimated that three to five million people are affected in Germany. COPD therapy, its causes and the course of the disease have not yet been fully researched. For example, there is a lack of suitable biomarkers (indicators) that indicate a worsening of the disease. This would help to provide patients with a more suitable therapy at an earlier stage.
“Trash can” of the cell – proteasome as biomarker for COPD?
What could serve as a biomarker, an indicator of deterioration in COPD? The proteasome, or more precisely the immunoproteasome, is of increasing importance. This is the protein complex in the cell that is responsible for protein quality control. The proteasome acts as a kind of cleaning troop, cutting cell-specific and non-cell-specific proteins into small components (peptides) so that they can be recycled. Some of these "protein snippets" are also presented to the immune system. Specialized immune cells then recognize the components that do not belong there, for example when the protein is altered or does not belong to the body. After recognition, these diseased cells are then destroyed.
What we already know:
Proteasome function is impaired in the lung immune cells of COPD patients and can no longer effectively shred proteins. In both test tube and mouse experiments, we were also able to show that cigarette smoke causes a reduced activity of the proteasome and that this is associated with an inhibited immune response. Therefore, our hypothesis is that the immune response in COPD patients is not fully functional. This leads to the destruction of even more tissue in the lungs due to the accumulation of damaged proteins. In addition, the immune system can no longer be effectively alerted when foreign proteins multiply in the cell, as is the case with infections with viruses. This means that the disease progresses or that additional acute exacerbations occur when infections can no longer be adequately combated.
Our current investigations: data quality and protein quality
We compare the function and activity of the proteasome in the blood cells of COPD patients of different stages with that in the blood cells of healthy people (gender- and age-adapted). Here, we use the COPD patients of the COSYCONET cohort and the healthy study participants of the KORA cohort. The aim is to collect blood samples from 450 patients of the COSYCONET cohort – 150 from each of the three disease stages mild, moderate and severe (GOLD I, II and III to IV).
We are investigating these biosamples at the CPC-M for their proteasome function – and how this correlates with the progression of the disease with specific symptoms of COPD patients.
We are also investigating the extent to which concomitant diseases such as asthma, diabetes or obesity affect proteasome function and COPD symptoms.
Can clear signals from the proteasome predict the prognosis for COPD?
We hope that the proteasome function in the blood cells can serve as a clear biomarker for COPD. It could indicate in which COPD patients progression of the disease or an exacerbation (acute worsening) is expected. And it could provide information about the extent of comorbidities. In this respect, this project shows very well how findings and observations from basic research could benefit the patient.