COPD und Asthma
Klinik für PneumologieProjekte
P2R signalling in acute and chronic inflammatory airway disease
a) Purinergic receptors in the pathogenesis of asthma
Allergic asthma is one of the most common chronic diseases in western society. Over the last years others and we demonstrated that extracellular nucleotides such as ATP can modulates the recruitment and/or function of various cell types such as mast cells, eosinophils, neutrophils, CD4+ T-cells, blood-/alveolar-marcophages and dendritic cells, which play an important role in the induction and/or maintance of allergic airway inflammation. In addition we could recently show that extracellular ATP released into the airway of asthmatic patients and mice with experimental asthma indeed plays a crucial role in the induction and maintenance of allergic inflammation in asthma in vivo. Starting from these observations the aim of the project is to identify the precise P2R-subtypes involved and to elucidate whether targeting P2R might be a new therapeutic option for the treatment of asthma.
b) Purinergic receptors in the pathogenesis of COPD
Chronic obstructive pulmonary disease (COPD) is a major global health problem that has a large impact on quality of life for patients and their families. The major inflammatory cell types participating in COPD are neutrophils, macrophages and CD8+ T-lymphocytes. The aim of our group is to determine the involvement of purinergic receptors in the pathogenesis of COPD by using in vivo mouse model for cigarettes smoke induced lung inflammation and lung emphysema as well as material from COPD patients.
Funded by the Emmy-Noether Program of the DFG
Contact person:
Dr. Sanja Cicko and Prof. Dr. Marco Idzko
Purinergic receptors in the pathogenesis lung fibrosis
Idiopathic pulmonary fibrosis (IPF) is a disease with poor prognosis and no effective therapy currently available. The pathogenesis of this devastating disease is not fully understood. In the past, extracellular nucleotides, e.g. adenosine-5’-triphosphate (ATP) have gained attention as mediators of inflammation and immuno-regulation via purinergic receptor (P2R) signalling. Preliminary results showed that extracellular ATP levels are elevated in patients suffering from IPF or in mice with experimental lung fibrosis Thus aim of our group is to determine the involvement of purinergic receptors in the pathogenesis of IPF by using the BLM-induced lung fibrosis mouse model and BALF-cells and lung tissue from lung fibrosis patients.
Contact person:
Dr. Sanja Cicko and Prof Dr Marco Idzko
Non-invasive monitoring of airway inflammation – translational patient studies
Airway inflammation is a key component in the pathogenesis of common airway diseases such as bronchial asthma and COPD. In line with this, new inhaled and systemic drugs for these disease target various players in the inflammatory cascade; however, the monitoring of airway inflammation is not part of routine clinical care as interventions such as bronchoscopy are invasive and potentially pose patients at risk. Airway inflammation can be non-invasively assessed by the analysis of sputum, exhaled breath condensate or exhaled nitric oxide. These techniques do not exert stress on airways and can be easily repeated during follow-up visits. The information from non-invasive methods can valuably supplement routine clinical data including measurements of lung function or blood gases. Our group aims to utilize analysis of inflammatory markers in sputum supernatant (ELISA, luminescent and fluorescent detection) and gene/protein expression of inflammatory mediators in sputum cells to identify new anti-inflammatory targets such as purinergic receptors. As every day we treat patients with severe and/or difficult-to treat asthma and COPD at our in- and outpatient settings we also intensely study the value of non-invasive markers in identifying disease phenotypes and predicting exacerbations.
Contact person:
Madelon Hoßfeld and Prof Dr Marco Idzko