Clinical trial NCT03500822: Effects of Dynamic Hyperinflation on the Left-ventricular Diastolic Function in Healthy Male Subjects
Official title: Effects of Dynamic Hyperinflation on the Left-ventricular Diastolic Function in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: dynamic hyperinflation
diastolic dysfunction
COPD
Chronic Obstructive Pulmonary Disease
Metronome-paced Tachypnea
Expiratory-stenosis Breathing
Lead sponsor: Otto Wagner Hospital
Sponsor class: OTHER
First posted: 2018-04-18
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of this study is to identify whether actively induced dynamic hyperinflation can cause left-ventricular diastolic dysfunction in healthy male subjects in order to explore the mechanisms of developing cardiac dysfunctions in patients with COPD.

Detailed description: Cardiovascular diseases, especially left-ventricular diastolic dysfunction, are among the most frequent reasons for morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD).

Dynamic hyperinflation is one of the expected pathophysiological mechanisms in the multifactorial genesis of this left-ventricular diastolic dysfunction in patients with COPD.

The novel concept of Expiratory Stenosis Breathing (ESB) is based on the method of Metronome-Paced Tachypnea (MPT) of Cooper et al. Therefore the investigators use a metronome to indicate a specific breathing frequency (BF) and the relation of inspiration : expiration (I : E) in order to let subjects hyperinflate.

Subjects get split into two groups each hyperinflating three times for 90sec by one of the two methods before doing a cross-over and switch groups to do the same in the other group. At the end of the 90sec there is a measurement of the Inspiratory Capacity (IC) and an echocardiography in order to objectify dynamic hyperinflation respectively the change in diastolic function.

During ESB participants hyperinflate with a BF - 30/min and a I : E - 1 : 3. In addition they have to breathe through an expiratory-effective stenosis (3, 2 and 1,5mm) on the mouthpiece of the pneumotachograph to simulate the collapsing airways in COPD-patients. In contrast, during MPT subjects hyperinflate with a BF - 40/min, I : E - 1 : 1; BF - 40/min, I : E - 1 : 2; BF - 30/min, I : E - 1 : 2.

During the whole trial investigators measure Intrinsic Positive Endexpiratory Pressure (PEEPi) in order to objectify the dynamic hyperinflation more significantly.

The primary goal of this study is to assess if actively induced dynamic hyperinflation can affect diastolic function of the left ventricle.

Furthermore a correlation between the extent of dynamic hyperinflation and diastolic dysfunction should be quantified.

In addition measurement of PEEPi should validate the method of Metronome-paced Tachypnea (MPT) because the investigators hypothesize that this method does not simulate the pathophysiological circumstances in patients with COPD sufficiently.

Eligibility criteria: Inclusion Criteria:

* BMI \<27 kg/m2
* Lifelong nonsmoker (currently non-smoking and up to now less than 100 cigarettes)

Exclusion Criteria:

* Obstructive pulmonary diseases (asthma, COPD)
* Cardiovascular diseases (cardiac insufficiency, coronary heart diseases, hypertonia)
* Other relevant pulmonary or cardiac diseases
* Baseline E/A-ratio \<1

Primary outcomes:
measure: E/A-ratio (absolute change between tidal breathing and smallest stenosis)
timeFrame: At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
Secondary outcomes:
measure: E/E'-ratio
timeFrame: At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
measure: deceleration time of the E-wave transmitral (msec)
timeFrame: At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
measure: Maximal diastolic transtricuspid flow (m/sec)
timeFrame: At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
measure: Maximal late-systolic velocity of the lateral tricuspid valve in Tissue Doppler Imaging (cm/sec)
timeFrame: At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
measure: Inspiratory Capacity
timeFrame: At the end of each cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
measure: Dynamic Intrinsic Positive Endexpiratory Pressure:
timeFrame: During each entire cycle - tidal breathing as well as hyperinflation-intervention (each cycle is at least 90 seconds).
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Otto Wagner Spital, Dep. of Respiratory and Critical Care Medicine
Study officials:
affiliation: Department of Respiratory and Critical Care Medicine and Ludwig-Boltzmann Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna
name: Georg C Funk, Assoc. Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cooper CB, Calligaro GL, Quinn MM, Eshaghian P, Coskun F, Abrazado M, Bateman ED, Raine RI. Determinants of dynamic hyperinflation during metronome-paced tachypnea in COPD and normal subjects. Respir Physiol Neurobiol. 2014 Jan 1;190:76-80. doi: 10.1016/j.resp.2013.08.002. Epub 2013 Aug 27.
citation: Weigt SS, Abrazado M, Kleerup EC, Tashkin DP, Cooper CB. Time course and degree of hyperinflation with metronome-paced tachypnea in COPD patients. COPD. 2008 Oct;5(5):298-304. doi: 10.1080/15412550802363428.
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citation: Barr RG, Bluemke DA, Ahmed FS, Carr JJ, Enright PL, Hoffman EA, Jiang R, Kawut SM, Kronmal RA, Lima JA, Shahar E, Smith LJ, Watson KE. Percent emphysema, airflow obstruction, and impaired left ventricular filling. N Engl J Med. 2010 Jan 21;362(3):217-27. doi: 10.1056/NEJMoa0808836.
citation: Urban MH, Mayr AK, Schmidt I, Grasmuk-Siegl E, Burghuber OC, Funk GC. Effects of Dynamic Hyperinflation on Left Ventricular Diastolic Function in Healthy Subjects - A Randomized Controlled Crossover Trial. Front Med (Lausanne). 2021 May 4;8:659108. doi: 10.3389/fmed.2021.659108. eCollection 2021.