Clinical trial NCT05704101: NHFT Effects on Symptatheic Drive of Asthma Patients
Official title: Influence of Nasal High-flow Therapy (NHFT) on Ventilation and Sympathetic Drive in Patients With Asthma
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Asthma
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
Collaborators: name: ResMed
First posted: 2023-01-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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).

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Assessments of the sympathetic nerve activity axis (Non invasive)
timeFrame: 1 year
measure: Assessments of the sympathetic nerve activity axis (Invasive)
timeFrame: 1 year
Secondary outcomes:
measure: OSA severity
timeFrame: 1 year
measure: Determination of PH (pulmonary hypertension) and right HF (heart failure) severity
timeFrame: 1 year
measure: Comprehensive lung function and inspiratory muscle function testing as previously described by our group
timeFrame: 1 year
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: University Hospital RWTH Aachen-Department of Pneumology and Intensive Care
state: NRW
Study officials:
References:
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.
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.
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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.
citation: 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.
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.