Bronchodilators on the Exercise Capacity of Bronchiectasis Patients

Study Overview
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Brief Summary
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The bronchodilators (BD) have been widely used in bronchiectasis (BCE) therapeutic and have been shown to be effective in improving exercise capacity in patients with chronic obstructive pulmonary disease and asthma. However the BD effect on the exercise capacity of patients with BCE is poorly known. Besides, the respiratory mechanics pattern of the patients with BCE is not known nor its association with their physical activity level (PAL). Therefore, the hypothesis of this study is that BD are effective in improving exercise capacity of patients with BCE. The authors also propose to characterize the respiratory mechanics of the patients with BCE and to evaluate their PAL and its association with quality of life, as secondary aims.

Detailed Description
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This is a randomized, double-blind, crossover, placebo-controlled trial. Forty clinically stable patients with bronchiectasis (BCE), all sexes, 18 to 59 years, will be evaluated in two non-consecutive days. On the first day, anamnesis, anthropometric evaluation and lung function will be performed, followed by: Quality of Life Questionnaire-Bronchiectasis, Saint George questionnaire, modified Medical Research Council scale and social and economic status. Then, a cardiopulmonary exercise test (CPET) will be performed and after a rest period, a bronchodilator (BD) or placebo randomization will precede a constant load exercise test (CLET) with the respiratory mechanics assessment (OEP). Spirometry will be performed pre and post BD/placebo. Finally, the accelerometer will be coupled to the patient for 7 consecutive days, aiming to assess the PAL. On the second day, after at least one-week washout, the accelerometer will be collected and the patient will repeat the CLET with the respiratory mechanics assessment, at the opposite condition to the randomization. The randomization sequence will be generated by computer, and put in sealed and opaque envelopes by a volunteer not involved in the study. The BD or placebo will be administered by a volunteer not involved in the study, according to the randomization. The evaluator will not have access to information on which intervention (BD or placebo) was given prior to each CLET. A paired (anthropometric and social and economic status) healthy control group will be assessed by spirometry, CPET, and CLET and OEP, for comparing respiratory mechanics. In addition the participants will also use an accelerometer for 7 consecutive days. Data of endurance time from CLET, respiratory mechanics from OEP, dyspnea and vital signs will be assessed before and after both BD and placebo CLET. Data about onset of BCE, comorbidities and BCE medication will be collected from the patient's medical record. Data normality will be tested by Kolmogorov-Smirnov. Data comparison will be performed by t test or Wilcoxon and the association by Pearson or Spearman. Categorical data will be analyzed by qui-square test or Fischer. The significance level will be set to 5% for all tests.

Official Title
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Effect of Bronchodilators on the Exercise Capacity of Bronchiectasis Patients

Conditions
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Bronchiectasis Adult

Intervention / Treatment
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* Drug: Bronchodilator (Ipratropium and Fenoterol)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All sexes 18 to 59 years Bronchiectasis diagnosis, according to thorax the Computed Tomography (Pasteur et al., 2010) Clinically stable (last 30 days without exacerbation/hospitalization) Air trapping on plethysmography (Residual Volume/Total Lung Capacity>125%) Smoking Load <10 pack-years Exclusion Criteria: Do not accept to participate Smoking Continuous oxygen use Pulmonary Rehabilitation program in the last 6 months Previous lung resection Uncontrolled cardiovascular disease Other respiratory chronic diseases Neurological or musculoskeletal disorders that limit exercise Cognitive deficits that limit comprehension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: On the first day, anamnesis, anthropometric evaluation and lung function will be performed, followed by: Quality of Life Questionnaire-Bronchiectasis, Saint George questionnaire, modified Medical Research Council scale and social and economic status. Then, a cardiopulmonary exercise test (CPET) will be performed and after rest, a bronchodilator (BD) or placebo randomization will precede a constant load exercise test (CLET) with the respiratory mechanics assessment (OEP). Finally, the accelerometer will be coupled to the patient for 7 consecutive days, aiming to assess the PAL. On the second day, after at least one-week washout, the accelerometer will be collected and the patient will repeat the CLET with the respiratory mechanics assessment, at the opposite condition to randomization.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bronchodilator<br>The intervention will be a combination of 2 drugs, ipratropium (20 mcg) and fenoterol (50mcg). Ipratropium is an anticholinergic bronchodilator, and fenoterol is a beta-agonist bronchodilator. The medication will be delivered to the patient via an inhaler device with spacer, at leat 20 minutes before the constant load exercise test (CLET). Patient will be asked for a total exhalation, followed by an appropriate spacer mouthpiece placement and the first of eight puffs (30 seconds interval between puffs) will be delivered through the opposite extremity of the spacer. Patient will be instructed to perform five tidal volume breaths for each puff. | Drug: Bronchodilator (Ipratropium and Fenoterol)<br>* 8 puffs of Ipratropium (20mcg) and Fenoterol (50mcg) via an inhaler device with a spacer (30 seconds interval between puffs) in 5 tidal volume breaths each puff.<br>* Other names: duovent;|
| Placebo Comparator: Placebo<br>The placebo will be delivered via an inhaler device with spacer (identical to the bronchodilator device), at least 20 minutes before the constant load exercise test (CLET). Patient will be asked for a total exhalation, followed by an appropriate spacer mouthpiece placement and the first of eight puffs (30 seconds interval between puffs) will be delivered through the opposite extremity of the spacer. Patient will be instructed to perform five tidal volume breaths for each puff. | Other: Placebo<br>* 8 puffs of placebo via an inhaler device with a spacer (30 seconds interval between puffs) in 5 tidal volume breaths each puff.<br>|
| No Intervention: Control<br>A paired healthy control group will be assessed by a constant load exercise test (75% from maximal load achieved on the cardiopulmonary exercise test) concomitant to the optoelectronic plethysmography to compare mechanical respiratory parameters to the bronchiectasis patients during the placebo assessment. In addition they will also use an accelerometer for 7 consecutive days. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endurance time | Endurance time will be assessed by the constant load exercise test (CLET). The CLET will be performed with 75% of maximal load (W) achieved on the cardiopulmonary exercise test (CPET). The CLET will be performed at a cycloergometer and the end of the CLET will be determined by the exertion (modified Borg Scale 9-10) or the required pedaling rate (60/min.) could not be kept up for 10 seconds. | 60 seconds | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchiectasis, Bronchodilators Agents, Exercise/Physical Activity, Respiratory Mechanics