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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease; Acute Exacerbation of COPD
• Intervention / Treatment: 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)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hung Yu Huang; Phone Number: 8470 + 886 33281200; Email: b9202071@cgmh.org.tw

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Hung Yu Huang; Phone Number: 8470 + 886 33281200; Email: b9202071@cgmh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NPV group; 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); 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.; Behavioral: breathing training, and an educational program (relaxation techniques and a home pacing walking exercise); 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)
Active Comparator: Control group; 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); 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Huang HY, Chou PC, Joa WC, Chen LF, Sheng TF, Lin HC, Yang LY, Pan YB, Chung FT, Wang CH, Kuo HP. Pulmonary rehabilitation coupled with negative pressure ventilation decreases decline in lung function, hospitalizations, and medical cost in COPD: A 5-year study. Medicine (Baltimore). 2016 Oct;95(41):e5119. doi: 10.1097/MD.0000000000005119.
• Huang HY, Lo CY, Yang LY, Chung FT, Sheng TF, Lin HC, Lin CW, Huang YC, Chang CJ, Chung KF, Wang CH. Maintenance Negative Pressure Ventilation Improves Survival in COPD Patients with Exercise Desaturation. J Clin Med. 2019 Apr 25;8(4):562. doi: 10.3390/jcm8040562.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2021
• Primary Completion (Anticipated): April 10, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Chronic obstructive pulmonary disease; Acute Exacerbation; Negative-pressure ventilation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 201902168B0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The IRB of Chang Gung Memorial Hospital does not permit to share IPD in this project.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No