• R Ryan, A Spathis, A Clow, M Fallon, and S Booth.
• Palliative Care Department, Box 63, Elsworth House, Cambridge University Hospitals NHS Foundation Trust, Hill's Road, Cambridge CB2 0QQ, United Kingdom. Electronic address: richella.ryan@addenbrookes.nhs.uk.
• Med. Hypotheses. 2014 Aug 1; 83 (2): 232-7.

AbstractBreathlessness is a common and distressing symptom in advanced cardiorespiratory disease, with recognised psychological, functional and social consequences. The biological impact of living with chronic breathlessness has not been explored. As breathlessness is often perceived as a threat to survival, we propose that episodic breathlessness engages the stress-response, as regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, we hypothesise that chronic breathlessness causes excessive stimulation of the HPA axis, resulting in dysfunctional regulation of the HPA axis and associated neuropsychological, metabolic and immunological sequelae. A number of observations provide indirect support for this hypothesis. Firstly, breathlessness and the HPA axis are both associated with anxiety. Secondly, similar cortico-limbic system structures govern both breathlessness perception and HPA axis regulation. Thirdly, breathlessness and HPA axis dysfunction are both independent predictors of survival. There is a need for direct observational evidence as well as experimental data to investigate this hypothesis which, if plausible, could lead to the identification of a new biomarker pathway to support breathlessness research.Copyright © 2014 Elsevier Ltd. All rights reserved.

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