Respiratory Drive Response in COPD Patients During Exercise With Non Invasive Ventilation (NIV).

Study Overview
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Brief Summary
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A constant load exercise during 10 minutes will be performed in a group of Chronic Obstructive Pulmonary Disease patients, in a basal condition (spontaneous breathing); under noninvasive mask ventilation and with high flow nasal cannula. With the aim of reducing dyspnea, increasing exercise tolerance, and unload respiratory muscles, three exercises will be compared in terms of use of respiratory muscles and neural drive measured with paraesternal electromyography.

Detailed Description
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Exercise in chronic obstructive pulmonary disease is limited by dynamic hyperinflation and respiratory muscle overloadleading to severe dyspnea. During exercise, the increase in neural respiratory drive is notable to match ventilatory demand, correlated with breathlessness. Non-Invasive Ventilation may improve neural respiratory drive uncoupling and exercise tolerance. The aim of this study will be prove if Non-Invasive Ventilation and High flow nasal cannula during exercise reduces neural respiratory drive and improves dyspnea, measured with paraesternal electromyography

Official Title
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Non-Invasive Ventilation (NIV) Effect on Neurorespiratory Coupling in Chronic Obstructive Pulmonary Disease During Exercise (COPD).

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Other: Exercise with spontaneous ventilation.
* Device: Exercise with NIV
* Device: Exercise with HFNC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe COPD or cystic fibrosis (with an obstructive pattern and air trapping) on the waiting list for a lung transplant, assessed by the Lung Transplant Unit of the 12 de Octubre University Hospital. Diagnostic criteria for COPD according to the GOLD and residual volume greater than 120% of theoretical Evidence of developing dynamic air trapping by analyzing flow / volume curves during physical exercise. Patients already adapted to home noninvasive mechanical ventilation (NIV) waiting for transplantation. Exclusion Criteria: Presence of comorbidities that limit the patient's physical effort capacity (uncontrolled ischemic heart disease, severe pulmonary hypertension, neuromuscular disease). Refusal of treatment with NIV, or inclusion in the study. Inability to perform the proposed exercise in basal conditions and with ventilation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort<br>All patients will be performed a basal test that consist on continuous cyclergometer exercise, under constant load, with spontaneous breathing, after that the same exercise protocol performed will be carried out under non-invasive ventilation (NIV test). Parameters will be titrated previosuly. Finally the patient will perform the same exercise at a constant load under high flow oxygen therapy ( HFNC test). | Other: Exercise with spontaneous ventilation.<br>* Patients will perform 10 minutes, constant load, exercise in a cycloergometer. To set the load, a baseline incremental effort test will be performed previously (VISIT 1). Then, in a separate day (VISIT 2), the subject will perform 10 minutes cycling at the 75% load of that determined as maximum in VISIT 1, at a constant rate of 30 to 35 pedal revolutions per minute, in spontaneous breathing, with low flow oxygen through conventional nasal cannula adjusted to achieve SpO2 between 92to 94%<br>Device: Exercise with NIV<br>* VISIT 2 Non invasive mask ventilation: parameters will be titrated during a free cycling period at the end of the spontaneous breathing exercise. Then, in a separate day (VISIT 3), with the same constant load, cycling cadence and under NIV, the patient will perform 10 min of cycling.<br>Device: Exercise with HFNC<br>* With constant flows of 50 lpm and with FiO2 adjusted according to SPO2, to obtain a constant saturation between 92 and 94%. The same pedaling load and frequency will be maintained, with similar variables collected.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Neural ventilator (NVU) (%) | the peak value (on the baseline) of the maximum muscle activity ( Root mean square EMG value in mV), both diaphragmatic (EMGDimax) and parasternal (EMGparamax) in the máximum intentional ventilation and maximum inspiratory peak (MIP) will be taken. This value will be consider 100% and based on this mean EMG will be calculate for a normalized EMGdi (RMS) and paraesternal in each ventilatory situation (spontaneous ventilation or under NIV). At each effort point (in each minute of the exercise protocol), the relationship between the normalized EMG value (parasternal and Diaphragmatic) and the tidal volume (obtained by integral of flow signal by means of a pneumotachograph connected to the VM -in NIV- or oronasal hermetic mask -in Vesp). To facilitate the interpretation of the expired TV, the mask without leakage will be used with the intentional leak connected in the circuit, before the pneumotachograph. | 24 hours, 48 hours, 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Borg Scale Dyspnea evolution (points) | Degree of dyspnea will be determined by this validated scale with a result between 1 and 10 points.0: Not at all 0.5: Very, very light (hardly noticeable) 1: Very light, 2: Light, 3: Moderate , 4: Somewhat intense, 5: Intense, 6: Between 5 and 7, 7: Very intense, 8: Between 7 and 9, 9: Very, very intense (almost maximum ), 10: Maximum | Basal value at day 1 and every 60 seconds during the exercise | 
| Borg Scale Dyspnea evolution (points) | Degree of dyspnea will be determined by this validated scale with a result between 1 and 10 points.0: Not at all 0.5: Very, very light (hardly noticeable) 1: Very light, 2: Light, 3: Moderate , 4: Somewhat intense, 5: Intense, 6: Between 5 and 7, 7: Very intense, 8: Between 7 and 9, 9: Very, very intense (almost maximum ), 10: Maximum | 24 hours later than day 1 (day 2) during the exercise every 60 seconds | 
| Borg Scale Dyspnea evolution (points) | Degree of dyspnea will be determined by this validated scale with a result between 1 and 10 points.0: Not at all 0.5: Very, very light (hardly noticeable) 1: Very light, 2: Light, 3: Moderate , 4: Somewhat intense, 5: Intense, 6: Between 5 and 7, 7: Very intense, 8: Between 7 and 9, 9: Very, very intense (almost maximum ), 10: Maximum | 48 hours later than day 1 (day 3) during the exercise every 60 seconds | 
| Borg Scale Dyspnea evolution (points) | Degree of dyspnea will be determined by this validated scale with a result between 1 and 10 points.0: Not at all 0.5: Very, very light (hardly noticeable) 1: Very light, 2: Light, 3: Moderate , 4: Somewhat intense, 5: Intense, 6: Between 5 and 7, 7: Very intense, 8: Between 7 and 9, 9: Very, very intense (almost maximum ), 10: Maximum | 72 hours later than day 1 (day 4) during the exercise every 60 seconds | 
| Transcutaneous pCO2 Final - inicial (mmHg) | Transcutaneous monitor uses a noninvasive technique to measure the skin-surface partial pressure of carbon dioxide (PtcCO2) | Basal value at day 1 during the exercise | 
| Transcutaneous pCO2 Final - inicial (mmHg) | Transcutaneous monitor uses a noninvasive technique to measure the skin-surface partial pressure of carbon dioxide (PtcCO2) | During the exercise at day 2 ( 24 hours later than day 1) | 
| Transcutaneous pCO2 Final - inicial (mmHg) | Transcutaneous monitor uses a noninvasive technique to measure the skin-surface partial pressure of carbon dioxide (PtcCO2) | During the exercise at day 3 (48 hours later than day 1) | 
| Transcutaneous pCO2 Final - inicial (mmHg) | Transcutaneous monitor uses a noninvasive technique to measure the skin-surface partial pressure of carbon dioxide (PtcCO2) | During the exercise at day 4 (72 hours later than day 1 ) | 
| Total Training time (pedaling, minutes) | Total Time that the patient remains pedaling | During the exercise at day 2 ( 24 hours later than day 1) | 
| Total Training time (pedaling, minutes) | Total Time that the patient remains pedaling | During the exercise at day 3 ( 48 hours later than day 1) | 
| Total Training time (pedaling, minutes) | Total Time that the patient remains pedaling | During the exercise at day 4 ( 72 hours later than day 1) | 
| Stops (n) | Number of stops that the patient performs during the test | During the exercise at day 2 ( 24 hours later than day 1) | 
| Stops (n) | Number of stops that the patient performs during the test | During the exercise at day 3 ( 48 hours later than day 1) | 
| Stops (n) | Number of stops that the patient performs during the test | During the exercise at day 4 ( 72 hours later than day 1) | 
| Ineffective efforts % | Porcentage of ineffective efforts during the exercise | During the exercise at day 2 ( 24 hours later than day 1) | 
| Ineffective efforts % | Porcentage of ineffective efforts during the exercise | During the exercise at day 3 ( 48 hours later than day 1) | 
| Ineffective efforts % | Porcentage of ineffective efforts during the exercise | During the exercise at day 4 ( 72 hours later than day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Noninvasive Ventilation, Exercise