Respiratory Muscle Fatigue at Different Breathing Modes

Study Overview
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Brief Summary
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The study aims at investigating if time to respiratory muscle fatigue and metabolism are influenced by the pressure wave form mode applied during resistive breathing.

Detailed Description
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In healthy subjects fitted with a nasogastric double balloon catheter and breathing at a resistance, the investigators will measure time to failure, Borg ratings, VO2, VCO2, flow, esophageal-, gastric- and airway-pressure. This will be done during breathing at either a square wave or triangle wave pressure waveform, in random order and trials separated by >two days. Further respiratory muscle fatigue will be investigated pre and post intervention by maximal esophageal pressure generation (voluntary and with cervical magnetic stimulation).

Official Title
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Does Inspiratory Pressure Wave Form Influence Respiratory Muscle Fatigue and Metabolism During Resistive Breathing

Conditions
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Healthy

Intervention / Treatment
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* Other: Square wave breathing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men or women Age ≥18 and ≤60 years BMI ≥ 20 and ≤30 Exclusion Criteria: Drug addiction defined as the use of cannabis, opioids or other drugs Previous and present neurologic (e.g. ataxia), musculoskeletal (e.g. muscular dystrophy) or mental illnesses (e.g. schizophrenia) History of mechanical ventilation, COVID-19 with respiratory complications, lung cancer Part of lung resected Presence of dyspepsia/heart-burn/abdominal pain Presence of esophageal varices Presence of liver disease Presence of esophageal hernia Pregnancy Failure to comply with transcranial magnetic stimulation adult safety screen History of epilepsy, metal implants in head or jaw Acute or chronic lung diseases, e.g. asthma, COPD, bronchitis etc. Lack of ability to cooperate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Square wave breathing|difference in time to failure from the two breathing modes|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to task failure (Tlim) | The time (s) from the subject starts to breathe under the experimental condition, and until task failure will be measured. Task failure is defied by either subject intolerance to continue or by lacking ability of the subject to maintain the target pressure and/or timing. From a previous publication (Bellemare and Grassino, JAP, 1982), it is estimated that subjects will reach Tlim between 30min to 1 hour. If breathing is continued after 1 hour, task failure will not happen as breathing can be continued indefinitely. | Up to two months between the two different breathing trials (randomized order) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory muscle pressures | Respiratory muscle pressure will be measured by esophageal and gastric pressure (in cmH2O) using a naso gastric catheter fitted with double balloons (Nutrivent) connected to a pressure sensor (ICU lab, KleisTek). | Up to two months between the two different breathing trials (randomized order) | 
| Tidal volume | Tidal Volume (ml) will be measured with a flowsensor (Hans Rudolph) through a pressure box (ICU lab, KleisTek) | Up to two months between the two different breathing trials (randomized order) | 
| Respiratory work | Work of breathing (j), will be calculated from outcome measure 2 and 9 (pressure (cmH2O) and insp. and expiratory time (s)). Measured with pressure box (ICU lab, KleisTek) | Up to two months between the two different breathing trials (randomized order) | 
| Ratings of perceived exertion | Borg Dyspnea Scale, from 0-10 where 0 is no effort at all and 10 is maximal breathing effort. | Up to two months between the two different breathing trials (randomized order) | 
| Metabolism | Energy expenditure calculated from VO2 (ml/min) nad VCO2 (ml/min) with e.g Weir equation. VO2 and VCO2 are measured with Beacon (Mermaid care). | Up to two months between the two different breathing trials (randomized order) | 
| Respiratory rate | Respiratory rate (breaths/min) will be measured with a flowsensor (Hans Rudolph) through a pressure box (ICU lab, KleisTek) | Up to two months between the two different breathing trials (randomized order) | 
| Minute ventilation | Minyte ventilation (l/min) will be measured with a flowsensor (Hans Rudolph) through a pressure box (ICU lab, KleisTek) | Up to two months between the two different breathing trials (randomized order) | 
| Insp. and expiratory time | Insp. and expiratory time (s) will be measured with a flowsensor (Hans Rudolph) through a pressure box (ICU lab, KleisTek) | Up to two months between the two different breathing trials (randomized order) |