Sympathetic Nerve Activity Predictors in Patients With Chronic Obstructive Pulmonary Disease (SNAP-COPD)

RWTH Aachen University

Status

Enrolling

Conditions

Sympathetic Nervous System Diseases

COPD

Catecholamine; Overproduction

Treatments

Diagnostic Test: Determination of PH and right HF severity

Diagnostic Test: Assessments of the sympathetic nerve activity axis

Diagnostic Test: OSA severity

Diagnostic Test: Assessment of systemic inflammation

Diagnostic Test: Comprehensive lung function and inspiratory muscle function testing.

Study type

Observational

Funder types

Other

Identifiers

NCT04849806

CTCA 20-423

Details and patient eligibility

About

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:

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

Full description

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.

Potentially obstructive sleep apnea (OSA) with not only repetitive obstructions but also additional hypoxia and poor sleep quality additively increase SNA in COPD. In addition, inspiratory muscle dysfunction (if adequately measured by magnetic diaphragm stimulation studies and comprehensive diaphragm ultrasound) with related hypercapnia, pulmonary hypertension (PH) and systemic inflammation all likely also impact on SNA in COPD.

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

In COPD, concomitant OSA with poor sleep is independently associated with increased SNA,.
PH, inspiratory muscle dysfunction and systemic inflammation describe a COPD phenotype characterised by increased SNA, manifesting differently.

To test these hypotheses COPD patients without an established cardiovascular disease will be enrolled and the extent, nature and mechanism of SNA increase compared with healthy controls matched in a 3:1 ratio for age, sex and body mass index (BMI).

Invasive assessment of muscle SNA to the point of single unit recordings with analysis of single postganglionic sympathetic firing, and hence SNA drive to the peripheral vasculature, is the gold standard for quantification of SNA in humans but is only available in a few centres worldwide because it is costly, time consuming and requires a high level of training.

A small substudy will investigate the short term acute treatment effects of non-invasive ventilation and oxygen supplementation on SNA in patients with COPD.

Enrollment

135 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Age ≥ 18
Ability and willingness to give informed consent to participate in the study

Exclusion criteria

Atrial fibrillation
Active pacing of the heart by a cardiac pacemaker (i.e. no intrinsic heart rate)
Clinically pre-established cardiovascular disease (e.g. arterial hypertension or systolic heart failure)
In-patient stay in the hospital within the last 4 weeks prior to the study examination date

Trial design

135 participants in 2 patient groups

COPD patients (n=100)

Description:

The following parameters will be determined in 100 consecutive patients with COPD without established cardiovascular disease (i.e. without an indication for beta blocker therapy or other pharmacological treatments attacking on the neurohormonal pathways like angiotensin-converting enzyme inhibitors or mineralocorticoid receptor antagonists). 1. OSA severity. 2. Determination of PH and right HF severity (defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography; 3. Comprehensive lung function and inspiratory muscle function testing ;Assessment of daytime hypoxia (PaO2 \<55 mmHg) and hypercapnia (PaCO2 \>45 mmHg) using capillary blood gas analysis; 4. Assessment of systemic inflammation

Treatment:

Diagnostic Test: Comprehensive lung function and inspiratory muscle function testing.

Diagnostic Test: Assessment of systemic inflammation

Diagnostic Test: OSA severity

Diagnostic Test: Assessments of the sympathetic nerve activity axis

Diagnostic Test: Determination of PH and right HF severity

Controls (n=35)

Description:

(and in a group of healthy controls \[3:1\] matched for age, sex and BMI).

Treatment:

Diagnostic Test: Comprehensive lung function and inspiratory muscle function testing.

Diagnostic Test: Assessment of systemic inflammation