Neuropsychological stratification of Chronic Obstructive Pulmonary Disease: building affect into clinically relevant neuro-biomarkers of breathlessness

BackgroundChronic breathlessness profoundly affects quality of life for its sufferers. Often, reported breathlessness is inconsistent with airway pathophysiology and objective disease markers. 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 perceptual modulators. Therefore, here we have developed a model capable of exploring these relationships aiding patient stratification and revealing clinically-relevant neuro-biomarkers. MethodsA cohort of 100 participants with mild-to-moderate chronic obstructive pulmonary disease (COPD) underwent a comprehensive assessment that included functional brain imaging while viewing and rating breathlessness-related word cues, self-report questionnaires and clinical measures. ResultsUsing an exploratory factor analysis across psychological and physiological measures, we identified two distinctive neuropsychological behavioural profiles that differed across four key factors corresponding to mood, symptom burden, and two capability measures. These profiles stratified participants into high and low symptom groups, which did not differ in spirometry values. The low symptom load group demonstrated greater FMRI activity to breathlessness-related word cues in the anterior insula. ConclusionsOur findings reveal two clear groups of individuals within our COPD cohort, divided by behavioural rather than clinical factors. Furthermore, indices of depression, anxiety, vigilance and perceived capability were linked to differences in brain activity within key regions thought to be involved in monitoring bodily sensations (interoception). These findings demonstrate the complex relationship between affect and interoceptive processing, providing the foundations for the development of targeted treatment programmes that harness clinical and symptom-relevant biomarkers.