NHFT Effects on Symptatheic Drive of Asthma Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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: SNA is increased in asthma patients. NHFT has a positive impact on the sympathetic drive resulting in decreased SNA.

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

Conditions
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Asthma

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Asthma patients (n=20) out of them 10 with mild, controlled and 10 with severe, uncontrolled asthma<br>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).<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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