NHFT Effects on Symptatheic Drive of Asthma Patients

Asthma Clinical Trial

— MSNA in Asthma  

Official title:

Influence of Nasal High-flow Therapy (NHFT) on Ventilation and Sympathetic Drive in Patients With Asthma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05704101
• Other study ID #: CTCA 22-274
• Status: Recruiting
• Start date: July 1, 2023
• Est. completion date: May 2024

Study information

• Verified date: November 2023
• Source: RWTH Aachen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

Asthma, being one of the major pulmonary diseases affects roughly 300 million people worldwide. This disease leads to airflow obstruction within the lung following chronic inflammation of the respiratory tract, which results in a wide range of symptoms. Overactivity of SNA has been already linked to patients with systolic heart failure and COPD. The investigators postulate that similar pathomechanism is prevalent in Asthma which leads to an overactivity of SNA.

Nasal High Flow Therapy (NHFT) is a recently developed form of oxygen therapy that delivers heated and humidified high-flow oxygen and gas mix through a nasal cannula. In comparison to conventional oxygen therapy, NHFT has been proven substantially beneficial due to additional effects like decreased oxygen dilution, increased FRC, dead space washout with CO2 removal, increased mucociliary function and generation of positive end-expiratory pressure (PEEP) which lead to significantly improved breathing mechanics often preventing the need for invasive machine ventilation (IMV) in various acute diseases. Furthermore, these mechanisms lead to the bronchodilation of small airways in primary obstructive pulmonary diseases like COPD. Positive benefits of NHFT, not only during an acute exacerbation but also with long-term stable disease have been already established in COPD. Similar effects could be expected in bronchial Asthma characterized by obstruction of small airways.

Thus, using a comprehensive, multimodal approach and state-of-the-art technology, this research project is designed to determine the prevalence, extent and nature of increased SNA in Asthma (AIM 1) and evaluate the impact of NHFT on sympathovagal balance in patients (AIM 2).

The project will address the following hypotheses:

1. SNA is increased in asthma patients.

2. NHFT has a positive impact on the sympathetic drive resulting in decreased SNA.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Clinically diagnosed Asthma

• 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 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

Related Conditions & MeSH terms

• Asthma

Locations

Country	Name	City	State
Germany	University Hospital RWTH Aachen-Department of Pneumology and Intensive Care	Aachen	NRW

Sponsors (2)

Lead Sponsor	Collaborator
RWTH Aachen University	ResMed

Country where clinical trial is conducted

Germany, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	OSA severity	Outcome measure: Apnea-hypopnea Index/h (AHI /h; Scale 0 - 150 /h with higher values indicating more severe sleep apnea).	1 year
Secondary	Determination of PH (pulmonary hypertension) and right HF (heart failure) severity	Outcome measure: TAPSE (tricuspid annular plane systolic excursion; mm).	1 year
Secondary	Comprehensive lung function and inspiratory muscle function testing as previously described by our group	Outcome measure: Sniff nasal pressure (SNIP; cmH2O).	1 year