Bronchodilators on the Exercise Capacity of Bronchiectasis Patients

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 their effect on the exercise capacity of patients with BCE is poorly known. Besides, their respiratory mechanics pattern is also not known neither their physical activity level (PAL). Therefore, the hypothesis of this study is that BD are effective in improving exercise capacity of BCE patients. We aim also to characterize their respiratory mechanics and to evaluate their PAL and its association to their quality of life.

This is a randomized, double-blind, crossover, placebo-controlled trial. Forty clinically stable bronchiectasis (BCE) patients, all sexes, 18 to 60 years, will be evaluated in two non-consecutive days. On the first day, anamnesis, anthopometric 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 brochodilator (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 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. 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 professional 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 they will also use an accelerometer for 7 consecutive days. BCE patients 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.

On the first day, anamnesis, anthopometric 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 brochodilator (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 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.

All the measurements will be performed by a blinded professional, who will be masked from randomization and other results. The randomization sequence will be generated by computer, and put in sealed and opaque envelopes by a volunteer not involved in the study. The bronchodilator (BD) or placebo will be administered by a professional 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.

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 oppositte extremity of the spacer. Patient will be instructed to perform five tidal volume breaths for each puff.

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 oppositte extremity of the spacer. Patient will be instructed to perform five tidal volume breaths for each puff.

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 plethismography 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.

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.

8 puffs of placebo via an inhaler device with a spacer (30 seconds interval between puffs) in 5 tidal volume breaths each puff.

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 end of the CLET will bedetermined by

Inclusion Criteria: All sexes 18 to 60 years Bronchiectasis diagnosis, according to thorax CT(Pasteur et al., 2010) Clinically stable (last 30 days without exacerbation/hospitalization) Air trapping on plethismography (RV/TLC>125%) Smoking Load <10 pack-years Exclusion Criteria: Do not accept to paticipate Smoking Continuous oxygen use Pulmonary Rehabilitation program in the last 6 months Previous lung ressection Uncontrolled Cardiovascular disease Other respiratory chronic diseases Neurological or musculoskeletal disorders that limit exercise Cognitive deficits that limit comprehension