NHFT Effects on Symptatheic Drive of Asthma Patients

NCT05704101 | Completed

• 1 other identifier: CTCA 22-274
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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). 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 diseases as in chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH). Comprehensive studies investigating sympathetic drive in Asthma as one of the major pulmonary diseases are still lacking. Furthermore, the intention of this study is to determine the impact of Nasal High Flow Therapy (NHFT) on SNA and assess respiratory muscle function using state-of-the-art techniques.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• Assessments of the sympathetic nerve activity axis (Non invasive)

  SVB (sympathovagal balance), HRV (Heart rate variability) and dBPV (diastolic blood pressure variability) 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 low frequency/high frequency (LF/HF), and the very low frequency component (VLF; 0.0-0.04 Hz) for both HRV and dBPV . Outcome measure: LF/HF ratio of HRV.

  1 year

• Assessments of the sympathetic nerve activity axis (Invasive)

  MSNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve. Outcome measure: Burst Incidence (MSNA Bursts /100 beats).

  1 year

Secondary Outcomes (3)

• OSA severity

  1 year

• Determination of PH (pulmonary hypertension) and right HF (heart failure) severity

  1 year

• Comprehensive lung function and inspiratory muscle function testing as previously described by our group

  1 year

Study Arms (2)

Asthma patients (n=20) out of them 10 with mild, controlled and 10 with severe, uncontrolled asthma

* Assessments of the SNA-axis. For this, HRV and dBPV will be analyzed using a 3-lead ECG and a continuous non-invasive arterial blood pressure signal. HRV and dBPV will be computed and presented as the high frequency , low frequency , their relative ratio (LF/HF), and the very low frequency component for both. * MSNA will be recorded via a tungsten microelectrode placed in the peroneal nerve. * NHFT at a flow rate of 20/30/40 liters/minute for 30 minutes respectively, with breaks of 15 minutes for all physiological variables to return to baseline. * OSA severity: defined as apnoea-hypopnoea index \[AHI\] \>15/h and obstructive apnoea index \[OAI\] \>5/h * Determination of PH and right HF severity (TAPSE ≤14 mm) and pulmonary arterial pressure (PAsys) using TTE. * Comprehensive lung function and inspiratory muscle strength and function testing as described previously by our group. * Assessment of systemic inflammation in blood samples.

Controls (n=10) (and in a group of healthy controls [2:1] matched for age, sex and BMI).

* Assessments of the SNA-axis. For this, HRV and dBPV will be analyzed using a 3-lead ECG and a continuous non-invasive arterial blood pressure signal. HRV and dBPV will be computed and presented as the high frequency , low frequency , their relative ratio (LF/HF), and the very low frequency component for both. * MSNA will be recorded via a tungsten microelectrode placed in the peroneal nerve. * NHFT at a flow rate of 20/30/40 liters/minute for 30 minutes respectively, with breaks of 15 minutes for all physiological variables to return to baseline. * OSA severity: defined as apnoea-hypopnoea index \[AHI\] \>15/h and obstructive apnoea index \[OAI\] \>5/h * Determination of PH and right HF severity (TAPSE ≤14 mm) and pulmonary arterial pressure (PAsys) using TTE. * Comprehensive lung function and inspiratory muscle strength and function testing as described previously by our group. * Assessment of systemic inflammation in blood samples.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Asthma patients (n=20) and Controls (n=10) 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 2:1 ratio for age, sex and body mass index (BMI).

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• ResMed: collaborator
• RWTH Aachen University: lead

Study Sites (1)

University Hospital RWTH Aachen-Department of Pneumology and Intensive Care

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Related Publications (6)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: mechanisms of action. Respir Med. 2009 Oct;103(10):1400-5. doi: 10.1016/j.rmed.2009.04.007. Epub 2009 May 21.

  PMID: 19467849 BACKGROUND

• Bruni A, Garofalo E, Cammarota G, Murabito P, Astuto M, Navalesi P, Luzza F, Abenavoli L, Longhini F. High Flow Through Nasal Cannula in Stable and Exacerbated Chronic Obstructive Pulmonary Disease Patients. Rev Recent Clin Trials. 2019;14(4):247-260. doi: 10.2174/1574887114666190710180540.

  PMID: 31291880 BACKGROUND

• Garrard CS, Seidler A, McKibben A, McAlpine LE, Gordon D. Spectral analysis of heart rate variability in bronchial asthma. Clin Auton Res. 1992 Apr;2(2):105-11. doi: 10.1007/BF01819665.

  PMID: 1638105 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2023
• First Posted: January 30, 2023
• Study Start: July 1, 2023
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)