Negative Pressure Ventilation-rehabilitation on Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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This investigator-initiated, prospective, single center, randomized, controlled clinical trial enrolled patients with stable Global Initiative for Chronic Obstructive Lung Disease stage II-IV chronic obstruction pulmonary disease. The primary outcome was 2-year acute exacerbation rates.

Detailed Description
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Pulmonary rehabilitation (PR) has been suggested to be positive effects on 6 min walking distance (6MWD), muscle force, cycle exercise endurance time, and quality of life. However, the literature still could not explain the role of PR in reducing systemic inflammation of chronic obstruction pulmonary disease (COPD) patients. A recent study found that PR with negative pressure ventilation (NPV) improved lung function, exercise capacity and reduced acute exacerbation rates in COPD patients. The objectives of this research are to design a prospective, randomized controlled trial to determine the clinical outcome of NPV-PR in COPD patients and to investigate if NPV-PR reduces systemic inflammation in patients with COPD. This investigator-initiated, prospective, single center, randomized, controlled clinical trial enrolled patients with stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II-IV COPD. NPV was targeted to reduce baseline blood carbon dioxide by at least 20% during NPV titration. Patients were randomly assigned (in a 1:1 ratio) to continue optimised standard treatment (control group) or to receive additional NPV-PR for at least 24 months (intervention group). The primary outcome was 2-year acute exacerbation rates. The lung function and walking distance will be assessed by six-minute walking tests and the severity of disease will be evaluated by high resolution computed tomography scores. Peripheral blood sample will be collected to analyze the inflammatory cytokines and oxidative markers. In the present prospective study, investigators hypothesize that NPV-PR would be superior to usual care in reducing the risk for acute exacerbations of COPD, hospitalisations and emergency visits over a 24-month period. This research will provide evidence for the role of NPV-PR in the management of COPD, and evidence for a role of systemic inflammation in disease progression of COPD. The results may provide certain insights into more effective treatments to inhibit the disease progression of COPD.

Official Title
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Negative Pressure Ventilation-rehabilitation on Acute Exacerbation and Associated Molecular Biomarkers and Cytokines in Chronic Obstructive Pulmonary Disease Over 2 Years

Conditions
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Chronic Obstructive Pulmonary Disease, Acute Exacerbation of COPD

Intervention / Treatment
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* Device: cuirass ventilator (cuirass diameter 21 cm or 34 cm, Dima Italia Srl.,Bologna, Italy)
* Behavioral: breathing training, and an educational program (relaxation techniques and a home pacing walking exercise)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COPD ((post-bronchodilation forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7) Optimal medical treatment according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)) at least 3 months before screening Exclusion Criteria: abnormalities of the thorax or the lung other than COPD, acute exacerbation within one month obesity with a body-mass index (BMI) ≥35 kg/m², malignant co-morbidities, severe heart failure (New York Heart Association stage IV), unstable angina, severe arrhythmias, neuromuscular diseases and/or impairment of basal brain nerve function with disturbed swallowing and choking and impaired general condition that could preclude regular follow-up visits.

Ages Eligible for Study
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Minimum Age: 20 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPV group<br>The hospital-based maintenance NPV program includes NPV support, breathing training, and an educational program (relaxation techniques and a home pacing walking exercise) in daily clinical practice. The patients in the NPV group undergo the hospital-based NPV once per week in the maintenance program at least three times per month. The patients received NPV with breathing training via a cuirass ventilator (cuirass diameter 21 cm or 34 cm, Dima Italia Srl.,Bologna, Italy) for 60 min, once per week. Breathing training consisted of breathing techniques (pursued-lipped, controlled, and diaphragmatic breathing). | Device: cuirass ventilator (cuirass diameter 21 cm or 34 cm, Dima Italia Srl.,Bologna, Italy)<br>* the hospital-based NPV once per week in the maintenance program at least three times per month. The ventilator is set to the control model with a frequency of 12 15 cycles/min, 30% of the ratio of inspiratory time to total breathing cycle time (Ti/Ttot), and delivery of negative pressures ranging from -20 to -35 cm H2O.<br>Behavioral: breathing training, and an educational program (relaxation techniques and a home pacing walking exercise)<br>* breathing training, and an educational program (relaxation techniques and a home pacing walking exercise) Breathing training consisted of breathing techniques (pursued-lipped, controlled, and diaphragmatic breathing)<br>|
| Active Comparator: Control group<br>Control group receives breathing training, and an educational program (relaxation techniques and a home pacing walking exercise) in daily clinical practice. Breathing training consisted of breathing techniques (pursued-lipped, controlled, and diaphragmatic breathing). | Behavioral: breathing training, and an educational program (relaxation techniques and a home pacing walking exercise)<br>* breathing training, and an educational program (relaxation techniques and a home pacing walking exercise) Breathing training consisted of breathing techniques (pursued-lipped, controlled, and diaphragmatic breathing)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COPD acute exacerbations rate | mild (required treatment with oral/systemic corticosteroids and/or antibiotics, without hospitalization) moderate (required treatment with oral/systemic corticosteroids and/or antibiotics, with emergency department visits) severe (required in-patient hospitalization) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the yearly rate of decline of forced expiratory volume in 1 second (FEV1) | the yearly rate of decline of FEV1 | 2 years | 
| the yearly rate of decline of 6 minute walking distance (6MWD) | the yearly rate of decline of 6MWD | 2 years | 
| Mortality | overall and pulmonary related | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic obstructive pulmonary disease, Negative-pressure ventilation, Acute Exacerbation