Pulmonary Rehabilitation After Exacerbation of Bronchiectasis

A Pilot Randomized Controlled Trial

James D. Chalmers; Megan L. Crichton; Gill Brady; Simon Finch; Mike Lonergan; Thomas C. Fardon

Disclosures

BMC Pulm Med. 2019;19(85) 

In This Article

Methods

The TRIBE study was a parallel group randomized controlled pilot trial. The study was prospectively registered at Clinicaltrials.gov- NCT02179983 and is reported according to CONSORT guidelines. The objective of the study was to determine the effectiveness of pulmonary rehabilitation in improving exercise capacity and health related quality of life following an exacerbation of bronchiectasis. As a pilot study, it was also intended to provide information to power a definitive future trial. The study was approved by the East of Scotland ethics committee and all patients gave written informed consent (13/ES/0062).

Inclusion and Exclusion Criteria and Patient Enrolment

Patients were enrolled when clinical stable and gave written informed consent. At enrolment patients agreed to contact the investigators at the onset of their next exacerbation.

The inclusion criteria were bronchiectasis confirmed on High Resolution CT scan; clinically significant bronchiectasis confirmed by a respiratory physician and at least one documented exacerbation within the last year. Patients were required to be independently mobile and therefore able to undertake pulmonary rehabilitation if randomized to this arm.

The exclusion criteria were Inability to give informed consent to participate; age < 18 years; a primary diagnosis of Chronic Obstructive Pulmonary Disease; significant comorbidity that would limit the ability to undertake pulmonary rehabilitation - i.e. Cerebrovascular, cardiovascular or musculoskeletal disease; known cystic Fibrosis; aortic aneurysm; recent myocardial infarction (within previous year) or unstable angina and patients having undergone pulmonary rehabilitation in the previous year.

Exacerbations

Exacerbations were defined as a sustained worsening of respiratory symptoms for > 48 h and a decision by a physician that antibiotic therapy is required.[18] EXACT-PRO diaries were used to validate the worsening of respiratory symptoms, but not as the definition of exacerbation for inclusion.

After onset of exacerbation patients contacted the investigators who provided a standardised antibiotic regimen for 14 days based on prior microbiology results according to international guideline recommendations.[15] Patients were then reviewed at day 14 (completion of antibiotic treatment) and were randomized at day 14 to either intervention or control.

Randomization

Patients were randomized using sealed opaque envelopes at 1:1 ratio to either pulmonary rehabilitation or standard care. Standard care consisted of guideline concordant ongoing management including instruction in daily chest physiotherapy.[19,20]

Pulmonary Rehabilitation

Patients randomized to pulmonary rehabilitation received a structured rehabilitation programme at Kings Cross Hospital in Dundee. Each patient was prescribed an individual programme and joined a group of approximately ten participants.

There were two supervised sessions per week and two 'homework' sessions for a total of 6 weeks. The class started with a gentle warm up and then moved into their own individual exercise programme based on their assessment and personal goals. Each programme contained a mixture of cardiovascular training – e.g. treadmill, bike, walking and strength training with free weights. Patients were exercised at 80% VO2max for cardiovascular work and one repetition maximum (RM) aiming for 8–10 reps for strength. All exercises were supervised and progressed by specialist physiotherapists and respiratory nurses. The exercise sessions were followed immediately by a cool-down, again led by the physio.

All patients attending the class were also given the following group educational activities; Benefits of exercise; Relaxed abdominal breathing and controlled breathing; Chest clearance techniques; Pathology of chronic lung disease (including bronchiectasis); Practical demo/advice on inhalers; Medications; Self-management; Smoking cessation; Pacing and energy conservation; Nutrition; Welfare rights and benefits; Maintenance options.

All patients received individual instruction in breathing strategies and chest clearance techniques to aid self-management. At the end of the six-week block of pulmonary rehab, patients were all encouraged to attend local maintenance groups including Active for Life (in local leisure centres) or circuit classes in various community settings (all supervised).

Endpoints

Endpoints were evaluated at baseline, onset of exacerbation, end of exacerbation (day 14), 8 weeks post-exacerbation and 12 weeks post-exacerbation.

The primary outcome was change in 6 min walk test distance from end of exacerbation (day 14 post antibiotic) to 8 weeks post-exacerbation.

Six min walk distance at 12 weeks post-exacerbation was a secondary endpoint. Additional secondary outcomes were; time to the next exacerbation, quality of life using the St Georges Respiratory Questionniare at 8 and 12 weeks, spirometry at 8 and 12 weeks, Cough symptoms measured using the Leicester cough questionnaire and COPD CAT questionnaire at 8 and 12 weeks and sputum microbiology.

As this was a pilot study, an additional objective was to identify the number of patients that would have to be recruited to demonstrate a clinically meaningful improvement in 6-min walk distance.

Statistical Analysis

Statistical analysis was performed using the Graphpad Prism v6 and R. Categorical variables are presented by frequencies and percentages and statistical differences were analysed using χ2 test or Fisher exact test when required. Continuous variables are presented as mean and standard deviation (SD) or median and interquartile range (IQR) when data are not distributed normally. Mean differences at each time point were compared using t-tests. As the objective of the study was to power a definitive future trial, no a priori power calculation was conducted. To produce estimates of how many patients would have to be recruited to achieve statistically significant results a semi-Bayesian approach, using frequentist tests but interpreting their results as probability distributions for parameter values, was used. These allowed for the uncertainty in the means and standard deviations estimated from the pilot data. Non-parametric bootstrap resamples of the data were drawn and used to construct empirical joint distributions of means and standard deviations. Simulated datasets of various sizes were then created from these distributions and used to estimate the probability of reporting statistically significant differences between group means for the 6-min walk test that were > 0 m, > 25 m, > 54 m, for different sample sizes. 25 m and 54 m were chosen as they are previously described minimum clinically important differences for the 6-min walk test.[21,22] All results are presented for the intention to treat population with a sensitivity analysis shown excluding patients with deviations from the protocol (per-protocol analysis). We defined statistical significance as a two-tailed p < 0.05 for all analyses.

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