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

Discussion

Pulmonary rehabilitation is an established intervention for the management of multiple respiratory disorders including COPD, interstitial lung disease and bronchiectasis.[15,23,24] For stable patients with bronchiectasis pulmonary rehabilitation has been strongly recommended by the 2017 European Respiratory Society Guidelines.[15] This was on the basis of a meta-analysis of 4 trials which each showed consistent benefits in terms of improved exercise capacity, improved symptoms and in one study, a reduction in exacerbations.[16]

Our study was designed to evaluate whether the benefits of pulmonary rehabilitation would extend to patients following an exacerbation of bronchiectasis. This was based, in part, on the observation that pulmonary rehabilitation after exacerbations of COPD carries substantial benefits including reduced risk of hospital admissions and mortality.[14]

Our study did not demonstrate significant benefits associated with pulmonary rehabilitation. 6-min walking distance and symptoms improved significantly between the immediate post-exacerbation period and 8 and 12 weeks post-exacerbation, but there were no significant differences between groups. For the primary outcome of 6-min walk distance in particular, the difference of 11 m at 8 weeks is unlikely to be clinically meaningful and there was no benefit of rehabilitation at 12 weeks with numerically greater improvement in the standard care group.

Our study was designed as a pilot trial to power a future larger trial if we found evidence to support the hypothesis that post-exacerbation rehabilitation was beneficial. Our analysis of the 27 subjects enrolled determined that while there is inevitably some uncertainty about the possible treatment effect given the small number of subjects enrolled, the variation in rates in recovery of 6-min walk distance indicated that more than 1000 subjects would need to be enrolled to achieve a > 80% probability of showing a clinically meaningful effect.

Our data make it unlikely, therefore, that pulmonary rehabilitation will be beneficial in this population of patients with exacerbations treated with oral antibiotics. Our study did not enrol patients with severe exacerbations requiring hospitalization and so does not exclude the possibility of a treatment benefit in this, or other populations not included in the present study. Our study did suggest a clinically meaningful difference, albeit not statistically significant, in respiratory symptoms measured by CAT. With such a small sample size it should be acknowledged that these differences may be the result of chance but they suggest that symptomatic improvement should be investigated in future trials of recovery from exacerbations.

Ours is not the only study that has failed to show benefit of pulmonary rehabilitation post-exacerbation. Greening et al. studied a cohort of 389 hospitalized individuals with multiple respiratory diseases including 20 subjects with bronchiectasis.[17] They randomized patients to early hospital based rehabilitation or standard care in hospital (within 48 h of hospital admission) consisting of daily supervised strength and aerobic training and neuromuscular electrical stimulation. The early rehabilitation failed to produce any clinical benefits in this trial and mortality was increased in the group that received rehabilitation at 12 months. The mechanism for this is unknown but as discussed by Spruit et al., appeared not be directly related to the intervention.[13,17]

Important strengths of our study include the well characterised patient population, the exclusion of patients with co-existing COPD where the role of pulmonary rehabilitation is established and the use of multiple endpoints to evaluate efficacy. Our study has important limitations. The sample size is small as this was a pilot study. The number of subjects enrolled (48) should have been sufficient to randomize at least 20 subjects to each arm but despite enriching for a population of patients with at least 1 exacerbation in the previous 12 months only 27 (56%) patients had an exacerbation during the subsequent year. This experience is entirely consistent with recent clinical trials in bronchiectasis. The RESPIRE trials of inhaled dry powder ciprofloxacin, for example, enrolled patients with a history of 2 more exacerbations per year but despite this history of frequent exacerbations, as many as 67% of patients in RESPIRE 2 did not experience an exacerbation in the subsequent year.[25–27] The reasons for this remarkable discordance between exacerbation reporting prior to trials and during the course of trials needs to be investigated in future studies. Randomization results in a possibility of unequal distribution of patients between arms in small studies and we experience this problem in TRIBE. Indeed twice as many subjects were randomized to the standard care arm as the intervention arm. Nevertheless the power calculations indicate that potentially thousands of patients would have been required to show clinically meaningful differences in the study. Our study was designed prior to the widespread use of the quality of life bronchiectasis questionnaire and so the SGRQ and CAT score were used instead. We are aware that these were not originally designed for bronchiectasis and future studies should establish if symptoms and quality of life improve when using bronchiectasis specific tools.[28–30] Our study was performed prior to the new consensus definition of bronchiectasis exacerbations.[18] Although compliance of those patients randomized to pulmonary rehabilitation was excellent for the supervised visits, we did not monitor adherence to the home training sessions. Adherence to pulmonary rehabilitation is suboptimal in clinical practice and so the results of randomized trials do not always transfer into benefits in real life.

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