Sympathetic Nerve Activity Predictors in Patients With Chronic Obstructive Pulmonary Disease

Summary

The project will be pursued in our respiratory, autonomic nervous system physiology laboratory (Respiratory, autonomic nervous system physiology laboratory, Department of Pneumology and Intensive Care Medicine, RWTH Aachen University Hospital; Head of Department: Professor Michael Dreher).

Overactivity of the sympathetic nerve activity (SNA) axis with "centrally" increased heart rate and peripheral vasoconstriction 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).

However, systematic analyses on this clinically relevant topic are currently lacking.

Thus, using a comprehensive, multimodal approach and state-of-the-art technology, this research project is designed to determine the extent and nature of increased SNA in COPD (AIM 1) and evaluate the underlying mechanisms (AIM 2).

The project will address the following hypotheses:

1. In COPD, concomitant obstructive sleep apnea is independently associated with increased SNA.
2. Precapillary pulmonary hypertension (PH), inspiratory muscle dysfunction and systemic inflammation describe a COPD phenotype characterised by increased SNA with a different subtype.

Conditions

• COPD
• Sympathetic Nervous System Diseases
• Catecholamine; Overproduction

Interventions

DIAGNOSTIC_TEST

Assessments of the sympathetic nerve activity axis

For assessment sympathovagal balance (SVB), HRV and dBPV will be analysed using a 3-lead electrocardiogram (sampling rate 1000Hz) and a continuous non-invasive arterial blood pressure signal (CNAP® technology, sampling rate 100Hz). HRV (ms2 based on continuously recorded variability in RR intervals) and (diastolic) BPV (expressed as mmHg2 based on continuously recorded variability in diastolic BP) will be computed by time domain analysis and by frequency domain analysis and presented as the high frequency component (HF; 0.15-0.4 Hz), low frequency component (LF; 0.04-0.15 Hz), their relative ratio (LF/HF), and the very low frequency component (VLF; 0.0-0.04 Hz) for both HRV and dBPV . Muscle SNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve. Plasma catecholamines will also be assessed.

DIAGNOSTIC_TEST

OSA severity

OSA is defined as apnoea-hypopnoea index \[AHI\] \>15/h and obstructive apnoea index \[OAI\] \>5/h) and sleep architecture

DIAGNOSTIC_TEST

Determination of PH and right HF severity

(defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography

DIAGNOSTIC_TEST

Comprehensive lung function and inspiratory muscle function testing.

Respiratory Muscle strength and function testing as previously established by our group and Assessment of daytime hypoxia (PaO2 \<55 mmHg) and hypercapnia (PaCO2 \>45 mmHg) using capillary blood gas analysis.

DIAGNOSTIC_TEST

Assessment of systemic inflammation

Based on blood samples taken.

Sponsors & Collaborators

• DFG - Deutsche Forschungs Gemeinschaft (German Research Foundation)

  collaborator UNKNOWN

• RWTH Aachen University

  lead OTHER

Principal Investigators

• Michael Dreher, Professor · RWTH Aachen University

• Jens Spiesshoefer, MD · RWTH Aachen University

• Binaya Regmi, MD · RWTH Aachen University

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-05-10

Primary Completion

2028-12-31

Completion

2028-12-31

Countries

• Germany

Study Locations