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Brain activity measured by functional brain imaging predicts breathlessness improvement during pulmonary rehabilitation

Abstract:

Background Chronic breathlessness in chronic obstructive pulmonary disease (COPD) is effectively treated with pulmonary rehabilitation. However, baseline patient characteristics predicting improvements in breathlessness are unknown. This knowledge may provide better understanding of the mechanisms engaged in treating breathlessness and help to individualise therapy. Increasing evidence supports the role of expectation (ie, placebo and nocebo effects) in breathlessness perception. In this study, we tested functional brain imaging markers of breathlessness expectation as predictors of therapeutic response to pulmonary rehabilitation, and asked whether D-cycloserine, a brain-active drug known to influence expectation mechanisms, modulated any predictive model.

Methods Data from 71 participants with mild-to-moderate COPD recruited to a randomised double-blind controlled experimental medicine study of D-cycloserine given during pulmonary rehabilitation were analysed (ID: NCT01985750). Baseline variables, including brain-activity, self-report questionnaires responses, clinical measures of respiratory function and drug allocation were used to train machine-learning models to predict the outcome, a minimally clinically relevant change in the Dyspnoea-12 score.

Results Only models that included brain imaging markers of breathlessness-expectation successfully predicted improvements in Dyspnoea-12 score (sensitivity 0.88, specificity 0.77). D-cycloserine was independently associated with breathlessness improvement. Models that included only questionnaires and clinical measures did not predict outcome (sensitivity 0.68, specificity 0.2).

Conclusions Brain activity to breathlessness related cues is a strong predictor of clinical improvement in breathlessness over pulmonary rehabilitation. This implies that expectation is key in breathlessness perception. Manipulation of the brain’s expectation pathways (either pharmacological or non-pharmacological) therefore merits further testing in the treatment of chronic breathlessness.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/thorax-2022-218754

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0003-2249-7612
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Psychiatry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Paediatrics
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Psychiatry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Psychiatry
Role:
Author
ORCID:
0000-0001-5130-7318


Publisher:
BMJ Publishing Group
Journal:
Thorax More from this journal
Volume:
78
Issue:
9
Pages:
852-859
Place of publication:
England
Publication date:
2022-12-26
Acceptance date:
2022-11-20
DOI:
EISSN:
1468-3296
ISSN:
0040-6376
Pmid:
36572534


Language:
English
Keywords:
Pubs id:
1317910
Local pid:
pubs:1317910
Deposit date:
2023-02-20

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