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| Name | Class |
|---|---|
| ResMed | INDUSTRY |
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Asthma patients (n=20) out of them 10 with mild, controlled and 10 with severe, uncontrolled asthma |
| ||
| Controls (n=10) (and in a group of healthy controls [2:1] matched for age, sex and BMI). |
|
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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).
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital RWTH Aachen-Department of Pneumology and Intensive Care | Aachen | North Rhine-Westphalia | 52074 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31461730 | Background | 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. | |
| 32396905 |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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Blood
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 |
| 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. |
| 31029769 | 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. |
| 19467849 | 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. |
| 31291880 | 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. |
| 1638105 | 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. |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |