Abstract
Rationale Current models of breathlessness often fail to explain disparities between patients' experiences of breathlessness and objective measures of lung function. While a mechanistic understanding of this discordance has thus far remained elusive, factors such as mood, attention and expectation have all been implicated as important modulators of breathlessness. Therefore, we have developed a model to better understand the relationships between these factors using unsupervised machine learning techniques. Subsequently we examined how expectation-related brain activity differed between these symptom-defined clusters of participants.
Methods A cohort of 91 participants with mild-to-moderate chronic obstructive pulmonary disease (COPD) underwent functional brain imaging, self-report questionnaires and clinical measures of respiratory function. Unsupervised machine learning techniques of exploratory factor analysis and hierarchical cluster modelling were used to model brain-behaviour-breathlessness links.
Results We successfully stratified participants across four key factors corresponding to mood, symptom burden and two capability measures. Two key groups resulted from this stratification, corresponding to high and low symptom burden. Compared to the high symptom load group, the low symptom burden group demonstrated significantly greater brain activity within the anterior insula, a key region thought to be involved in monitoring internal bodily sensations (interoception).
Conclusions This is the largest functional neuroimaging study of COPD to date and is the first to provide a clear model linking brain, behaviour and breathlessness expectation. Furthermore, it was possible to stratify participants into groups, which then revealed differences in brain activity patterns. Together, these findings highlight the value of multi-modal models of breathlessness in identifying behavioural phenotypes, and for advancing understanding of differences in breathlessness burden.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Finnegan has nothing to disclose.
Conflict of interest: Dr. Harrison has nothing to disclose.
Conflict of interest: Dr. Harmer reports other from p1vital, personal fees from Servier, personal fees from Eli-Lilly, personal fees from Astra Zeneca, personal fees from Lundbeck, other from Oxford Psychologists Ltd., outside the submitted work.
Conflict of interest: Dr. Herigstad has nothing to disclose.
Conflict of interest: Dr. Rahman reports personal fees from Rocket Medical U.K., outside the submitted work.
Conflict of interest: Dr. Reinecke has nothing to disclose.
Conflict of interest: Dr. Pattinson reports personal fees from Nektar therapeutics, outside the submitted work; In addition, Dr. Pattinson has a patent U.K. patent application titled “Use of cerebral nitric oxide donors in the assessment of the extent of brain dysfunction following injury pending.
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- Received April 28, 2020.
- Accepted April 4, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org
