Abstract
Background Recent randomised clinical trials in bronchiectasis have failed to reach their primary end-points, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis.
Methods We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV1) of ≥100 mL from baseline.
Results Cumulatively the three trials included 984 patients. Changes in FEV1, QoL and exacerbations were heterogeneous in all trials analysed. Improvements in QoL were not correlated to changes in FEV1 in the azithromycin and aztreonam trials (r= −0.17, p=0.1 and r=0.04, p=0.4, respectively) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QoL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV1 is not a responsive measure in bronchiectasis.
Conclusions Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV1 is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response, suggesting the need to develop biomarkers to identify responders.
Abstract
Response to treatment is heterogeneous in bronchiectasis, with no relationship between responses to different outcomes and without clinical predictors of response https://bit.ly/3lN6NwL
Footnotes
Author contributions: All authors participated in study design, data analysis and interpretation of the data. All authors were involved in writing and revising the manuscript before submission.
This study is registered at PROSPERO with identifier number CRD42018106167.
Conflict of interest: O. Sibila has nothing to disclose.
Conflict of interest: E. Laserna has nothing to disclose.
Conflict of interest: A. Shoemark has nothing to disclose.
Conflict of interest: L. Perea has nothing to disclose.
Conflict of interest: D. Bilton has nothing to disclose.
Conflict of interest: M.L. Crichton reports personal fees from AstraZeneca, outside the submitted work.
Conflict of interest: A. De Soyza reports grants, travel support to attend international congresses and lecture fees from AstraZeneca, Bayer, Chiesi, Grifols, GlaxoSmithKline, Insmed, Pfizer, Novartis, Medimmune and Zambon, outside the submitted work.
Conflict of interest: W.G. Boersma has nothing to disclose.
Conflict of interest: J. Altenburg has nothing to disclose.
Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Grifols, Boehringer Ingelheim and Insmed, grants from AstraZeneca and Bayer Healthcare, personal fees from Aradigm, Pfizer and Napp, outside the submitted work.
Support statement: This study was funded by the European Respiratory Society through the EMBARC2 consortium. EMBARC2 is supported by project partners AstraZeneca, Chiesi, Grifols, Insmed, Janssen, Novartis and Zambon. J.D. Chalmers is supported by the GSK/British Lung Foundation Chair of Respiratory Research. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 20, 2019.
- Accepted September 15, 2021.
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