Sympathetic Nerve Activity Predictors in Patients With Chronic Obstructive Pulmonary Disease

Официальное название

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

Обзор

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.

Подробное описание

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.

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 OSA with poor sleep is independently associated with increased SNA,. 2. 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.

Вмешательства

• Диагностический тест 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
• Диагностический тест OSA severity
  OSA is defined as apnoea-hypopnoea index \[AHI\] \>15/h and obstructive apnoea index \[OAI\] \>5/h) and sleep architecture
• Диагностический тест Determination of PH and right HF severity
  (defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography
• Диагностический тест 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.
• Диагностический тест Assessment of systemic inflammation
  Based on blood samples taken.

Первичные конечные точки

• Assessments of the sympathetic nerve activity axis (Non invasive) [Срок оценки: 2 years]
• Assessments of the sympathetic nerve activity axis (Invasive) [Срок оценки: 2 years]

Вторичные конечные точки (4)

• OSA severity [Срок оценки: 2 years]
• Determination of PH and right HF severity [Срок оценки: 2 years]
• Comprehensive lung function and inspiratory muscle function testing as previously described by our group [Срок оценки: 2 years]
• Assessment of systemic inflammation [Срок оценки: 2 years]

Критерии участия

Критерии включения

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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Германия · 1 центр

• RWTH Aachen University — Aachen

Публикации

• Spiesshoefer J, Becker S, Tuleta I, Mohr M, Diller GP, Emdin M, Florian AR, Yilmaz A, Boentert M, Giannoni A. Impact of Simulated Hyperventilation and Periodic Breathing on Sympatho-Vagal Balance and Hemodynamics in Patients with and without Heart Failure. Respiration. 2019;98(6):482-494. doi: 10.1159/000502155. Epub 2019 Aug 28. PMID 31461730
• Spiesshoefer J, Herkenrath S, Henke C, Langenbruch L, Schneppe M, Randerath W, Young P, Brix T, Boentert M. Evaluation of Respiratory Muscle Strength and Diaphragm Ultrasound: Normative Values, Theoretical Considerations, and Practical Recommendations. Respiration. 2020;99(5):369-381. doi: 10.1159/000506016. Epub 2020 May 12. PMID 32396905
• Spiesshoefer J, Henke C, Herkenrath S, Brix T, Randerath W, Young P, Boentert M. Transdiapragmatic pressure and contractile properties of the diaphragm following magnetic stimulation. Respir Physiol Neurobiol. 2019 Aug;266:47-53. doi: 10.1016/j.resp.2019.04.011. Epub 2019 Apr 25. PMID 31029769
• Dreher M, Neuzeret PC, Windisch W, Martens D, Hoheisel G, Groschel A, Woehrle H, Fetsch T, Graml A, Kohnlein T. Prevalence Of Chronic Hypercapnia In Severe Chronic Obstructive Pulmonary Disease: Data From The HOmeVent Registry. Int J Chron Obstruct Pulmon Dis. 2019 Oct 18;14:2377-2384. doi: 10.2147/COPD.S222803. eCollection 2019. PMID 31695357

Идентификаторы

NCT: NCT04849806 · CTCA 20-423

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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