Dissecting the Nature and Determinants of Sympathetic Nerve Activity in Patients with COPD

• Applicant: Privatdozent Jens Spiesshoefer, Ph.D.
• Subject Area: Pneumology, Thoracic Surgery
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570018574

Overactivity of the sympathetic nerve activity (SNA) axis is a known phenomenon in patients with systolic heart failure (HF) and has recently been described in patients with primary lung disease, as seen in chronic obstructive pulmonary disease (COPD).Thus, insights into the nature of, and factors involved in, increased SNA in COPD are urgently needed to help identify COPD patients who may benefit from individualised -blocker therapy and to understand autonomic nervous system dysfunction in COPD overall. Our group identified several factors that are associated with SNA increase in COPD, the most important of which is obstructive sleep apnoea (OSA), which is highly prevalent in COPD. Thus, using a comprehensive, multimodal approach and state-of-the-art technology in a sufficiently large sample for the first time, this research project is designed to determine the extent and nature (by measuring MSNA to the point of single unit recordings) of increased SNA in COPD (AIM 1) and evaluate the mechanisms underlying this association (AIM 2). The project will address the following hypotheses: 1. SNA is increased in people with COPD independently of concomitant cardiovascular disease.2. OSA, low FEV1, hypoxia, hypercapnia, pulmonary hypertension, systemic inflammation and inspiratory muscle weakness with physical inactivity are the key driver of increased SNA in COPD.This type of phenotyping of individuals with COPD is necessary because it will allow better selection of those suitable for inclusion in any future trial of a -blocker in COPD, which in turn would provide more definitive evidence for a potential therapeutic benefit of this type of medication in terms of reducing COPD exacerbations, and could help facilitate precision medicine for patients with COPD. Beyond this just like in HF SNA increase in COPD likely is associated with general autonomic nervous system dysfunction likely characterized not only by SNA increase but also by diminished parasympathetic function with alteration in both barorefex and chemoreflex-sensitivity all of which could also be made a translational therapeutic target once better understood and which will hence also be explored in the present project. To test the above hypotheses, individuals with COPD who do not have existing cardiovascular disease will be enrolled, and the extent, nature and mechanism of elevated SNA will be determined based on a comparison with healthy controls matched for age, sex and body mass index (BMI) in a ~3:1 ratio. The strength of this project relates to its multimodal and methodologically extensive approach of evaluating the nature and determinants of elevated SNA in COPD using the gold standard technique (measurement of muscle SNA) in the largest ever recruited patient cohort of 100 COPD patients to use this technique therein.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Michael Dreher; Professor Dr. Florian Kahles