Dissecting the Nature and Determinants of Sympathetic Nerve Activity in Patients With COPD
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 135
- 试验地点
- 1
- 主要终点
- Assessments of the sympathetic nerve activity axis (Non invasive)
研究概览
简要总结
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.
详细描述
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 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ability and willingness to give informed consent to participate in the study
排除标准
- •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
研究组 & 干预措施
COPD patients (n=100)
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).
- OSA severity.
- Determination of PH and right HF severity (defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography;
- 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;
- Assessment of systemic inflammation
干预措施: Assessments of the sympathetic nerve activity axis (Diagnostic Test)
COPD patients (n=100)
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).
- OSA severity.
- Determination of PH and right HF severity (defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography;
- 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;
- Assessment of systemic inflammation
干预措施: OSA severity (Diagnostic Test)
COPD patients (n=100)
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).
- OSA severity.
- Determination of PH and right HF severity (defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography;
- 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;
- Assessment of systemic inflammation
干预措施: Determination of PH and right HF severity (Diagnostic Test)
COPD patients (n=100)
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).
- OSA severity.
- Determination of PH and right HF severity (defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography;
- 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;
- Assessment of systemic inflammation
干预措施: Comprehensive lung function and inspiratory muscle function testing. (Diagnostic Test)
COPD patients (n=100)
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).
- OSA severity.
- Determination of PH and right HF severity (defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography;
- 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;
- Assessment of systemic inflammation
干预措施: Assessment of systemic inflammation (Diagnostic Test)
Controls (n=35)
(and in a group of healthy controls [3:1] matched for age, sex and BMI).
干预措施: Assessments of the sympathetic nerve activity axis (Diagnostic Test)
Controls (n=35)
(and in a group of healthy controls [3:1] matched for age, sex and BMI).
干预措施: OSA severity (Diagnostic Test)
Controls (n=35)
(and in a group of healthy controls [3:1] matched for age, sex and BMI).
干预措施: Determination of PH and right HF severity (Diagnostic Test)
Controls (n=35)
(and in a group of healthy controls [3:1] matched for age, sex and BMI).
干预措施: Comprehensive lung function and inspiratory muscle function testing. (Diagnostic Test)
Controls (n=35)
(and in a group of healthy controls [3:1] matched for age, sex and BMI).
干预措施: Assessment of systemic inflammation (Diagnostic Test)
结局指标
主要结局
Assessments of the sympathetic nerve activity axis (Non invasive)
时间窗: 2 years
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 .
Assessments of the sympathetic nerve activity axis (Invasive)
时间窗: 2 years
Muscle SNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve Plasma catecholamines will be assessed Muscle SNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve Plasma catecholamines will be assessed Muscle SNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve. Plasma catecholamines will be assessed
次要结局
- Determination of PH and right HF severity(2 years)
- OSA severity(2 years)
- Comprehensive lung function and inspiratory muscle function testing as previously described by our group(2 years)
- Assessment of systemic inflammation(2 years)
研究者
Jens Spießhöfer
Jens Spiesshoefer, MD, PhD Candidate, Group head Respiratory Physiology
RWTH Aachen University