Acute Effects of a Flutter Device in COPD

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation that is not fully reversible, and is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases, most commonly cigarette smoking. The disease affects not only the large central airways but also the small, more peripheral airways deeper into the lung, defined as less than 2 mm in diameter. Besides medical treatment, physiotherapy plays a major role in treatment and various methods have been suggested to remove airway of secretions. The flutter is a simple and small device shaped like a pipe that creates a positive expiratory pressure (PEP) and high frequency oscillation when the expired air passes through it. These vibrations are thought to mobilise airway secretions facilitating their clearance and improving breathing. Standard blowing tests, like spirometry, where patients blow forcedly into a machine, have previously been used to investigate the efficacy of flutter devices. However, spirometry assesses the damage of larger airways but not small airways, also known as the silent zone which, crucially, are specifically damaged in COPD. In this study the investigators hypothesise that because the flutter helps clear the airways from the excessive thick mucus produced by COPD patients, these patients may find it easier to breathe and have lower resistance to moving air in and out of their lungs. The main objective of this study is to compare the effect of a flutter or a sham device on small airways damage using impulse oscillometry (IOS), a non-invasive method that, contrary to other common blowing tests, measures small airway resistance during normal breathing. In addition, because COPD is characterised by inflammation, the investigators would also like to measure a gas the patients blow out, nitric oxide (NO) the levels of which reflect airway inflammation. This will give to investigators an insight into the relationship between airway inflammation and small airway function.

Detailed Description
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Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation that is not fully reversible. This limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Patients suffering from COPD may show pathologic changes not only in the large but also in the small airways, which are defined as less than 2mm in diameter. Airway inflammation may cause increased thick mucus secretions which can narrow the airways increasing the resistance to the airflow. Physiotherapy to remove secretions is indicated for patients with COPD who have regular sputum or those with thick secretions and various techniques and physiotherapy devices can be applied for the removal of secretions. The flutter is a simple and small device shaped like a pipe that creates a positive expiratory pressure (PEP) and high frequency oscillation as expired air passes through it. These vibrations and PEP are thought to mobilise airway secretions facilitating their clearance and improving airflow. The effects of the flutter device have been studied in different patient groups, but especially in lung diseases characterised by mucus hypersecretion such as COPD, cystic fibrosis and bronchiectasis. In COPD, even though the flutter device increases the volume of expectorated secretions, its beneficial effects on pulmonary function as assessed by spirometry and plethysmography are inconclusive. However, these standard lung function tests (such as spirometry) asses the large airways, but do not provide an accurate estimate of the small airways which have been described by some authors as the silent zone. The investigators hypothesise that the use of impulse oscillometry (IOS), a non-invasive technique that provides information on small airway resistance during normal breathing, may reveal the effect of the flutter device which may have not been accurately measured by spirometry in previous studies. In addition, the investigators would like to measure exhaled nitric oxide (NO) levels which reflect airway inflammation and may therefore be useful to determine the association between small airway disease and inflammation. In summary, the symptoms of patients with COPD improve following breathing exercises with a flutter device, however, the effect of this device on lung function is unclear. The investigators hypothesise that the combined use IOS and NO, would help understand and quantify the effects of the flutter device on the small airways disease in COPD. The main objective of this study is to measure the effect of a 30 minutes breathing exercise with a flutter device on airway resistance as assessed by impulse oscillometry in patients with COPD. The secondary objective is to investigate the association between inflammation, airway resistance and volume of secretions in COPD patients.

Official Title
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Acute Effects of a Flutter Device on Airways Resistance in Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Device: Flutter valve exercises
* Device: Flutter Sham exercises
* Device: Flutter and bronchodilator exercises


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - patients with COPD meeting the Global Initiative for Obstructive Lung Disease (GOLD) guidelines, with forced expiratory volume in the first second of expiration (FEV1) <80% predicted, FEV1/FVC ratio <70% predicted (FVC= forced vital capacity), and total lung capacity (TLC) >80% predicted), with or without sputum, will be included. The severity of COPD will be classified according to GOLD criteria: Stage I: mild FEV1/FVC<0.70 and FEV1>80% predicted; Stage II: moderate FEV1/FVC<0.70 and 50<FEV1<80% predicted; Stage III: severe FEV1/FVC<0.70 and 30<FEV1<50% predicted; Stage IV: very severe FEV1/FVC<0.70 and FEV1<30% or FEV1<50% predicted plus chronic respiratory failure, Exclusion Criteria: Patients with: Upper respiratory tract infection within the previous 28 days Treatment with antibiotics within 4 weeks prior the study Acute dyspnoea or hemoptysis Chest pain or recent history of rib fracture or pneumothorax Acute cardiovascular events in the previous 3 months Any history or evidence of renal, gastrointestinal or hepatic disease Any history and evidence of neuropsychiatric disease Alcohol, drug abuse or any other condition associated with poor compliance Breast feeding Pregnancy Other complications that hinder the completion of the tests Unable to provide written informed consent

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: flutter valve exercises<br>30 minutes of breathing exercises with flutter device | Device: Flutter valve exercises<br>* 30 minutes of flutter exercises<br>* Other names: Airway clearance technique;Device: Flutter and bronchodilator exercises<br>* Flutter + bronchodilator exercises with an interval of 3 to 5 days<br>|
| Sham Comparator: flutter-sham exercises<br>30 minutes of breathing exercise with flutter-sham device | Device: Flutter Sham exercises<br>* 30 minutes of flutter-sham exercises<br>* Other names: Airway clearance technique;Device: Flutter and bronchodilator exercises<br>* Flutter + bronchodilator exercises with an interval of 3 to 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airways Resistance (IOS) | Airways resistance were measured by impulse oscillometry (IOS) method. | Baseline test, after breathing exercises with flutter or flutter-sham device and after 20 minutes of rest | 
| Airways Resistance (IOS) - Reactance Area (Ax) | Airways resistance were measured by impulse oscillometry (IOS) method. | Baseline test, after breathing exercises with flutter or flutter-sham device and after 20 minutes of rest | 
| Airways Resistance (IOS) - Resonant Frequency (Fres) | Airways resistance were measured by impulse oscillometry (IOS) method. | Baseline test, after breathing exercises with flutter or flutter-sham device and after 20 minutes of rest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exhaled Nitric Oxide (FeNO) | Exhaled nitric oxide will be measured by chemiluminescence method. | Baseline and immediately after intervention | 
| Spirometry - Forced Expiratory Volume at 1 Second (FEV1) and Forced Vital Capacity (FVC) | Forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were measured using a dry wedge spirometer (Jaeger Co, Wurzburg, Germany) | Baseline and immediately after intervention | 
| Cough | Number of spontaneously reported cough episodes during each visit were collected. | During each session | 
| Secretion - Volume | Expectorated secretion volume during each visit were collected, weighted and classified with a purulence score. | During each session | 
| Secretion - Purulence Score | The expectorated secretion was collected, weighted and classified with a purulence score based on a previously described numerical visual scale, which ranges from 1 (mucoid) to 5 (yellow/green). Referee of the Purulence score: Barnes PJ, Dweik RA, Gelb AF, et al. Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest. 2010;138:682-692. | In each session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, physiotherapy care, lung function testing, inflammation