title: Salivary diurnal cortisol profiles in patients suffering from chronic breathlessness receiving supportive and palliative care services: A cross-sectional study.
abstract: Chronic breathlessness is a common source of psychological and physical stress in patients with advanced or progressive disease, suggesting that hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be prevalent. The aim of this study was to measure the salivary diurnal cortisol profile in patients receiving supportive and palliative care for a range of malignant and non-malignant conditions and to compare the profile of those experiencing moderate-to-severe disability due to breathlessness against that of patients with mild/no breathlessness and that of healthy controls. Saliva samples were collected over two consecutive weekdays at 3, 6, and 12h after awakening in 49 patients with moderate-to-severe breathlessness [Medical Research Council (MRC) dyspnoea grade ≥3], 11 patients with mild/no breathlessness (MRC dyspnoea grade ≤2), and 50 healthy controls. Measures of breathlessness, stress, anxiety, depression, wellbeing and sleep were examined concomitantly. The diurnal cortisol slope (DCS) was calculated for each participant by regressing log-transformed cortisol values against collection time. Mean DCS was compared across groups using ANCOVA. Individual slopes were categorised into one of four categories: consistent declining, consistent flat, consistent ascending and inconsistent. Controlling for age, gender and socioeconomic status, the mean DCS was significantly flatter in patients with moderate-to-severe breathlessness compared to patients with mild/no breathlessness and healthy controls [F (2, 103)=45.64, p<0.001]. Furthermore, there was a higher prevalence of flat and ascending cortisol profiles in patients with moderate-to-severe breathlessness (23.4%) compared to healthy controls (0%). The only variable which correlated significantly with DCS was MRC dyspnoea grade (rs=0.29, p<0.05). These findings suggest that patients with moderate-to-severe breathlessness have evidence of HPA axis dysregulation and that this dysregulation may be related to the functional disability imposed by breathlessness.
authors.affiliation: Cambridge University Hospitals NHS Foundation Trust, Palliative Care Department, Addenbrooke's Hospital, Hill's Road, Cambridge, CB2 0QQ, United Kingdom; Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge, CB2 0SR, United Kingdom. Electronic address: rcr41@medschl.cam.ac.uk.
authors.forename: Richella
authors.initials: R
authors.lastname: Ryan
authors.affiliation: Psychophysiology and Stress Group, University of Westminster, Department of Psychology, 115 New Cavendish Street, London, W1W 6UW, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Clow
authors.affiliation: Cambridge University Hospitals NHS Foundation Trust, Palliative Care Department, Addenbrooke's Hospital, Hill's Road, Cambridge, CB2 0QQ, United Kingdom; Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge, CB2 0SR, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Spathis
authors.affiliation: Psychophysiology and Stress Group, University of Westminster, Department of Psychology, 115 New Cavendish Street, London, W1W 6UW, United Kingdom.
authors.forename: Nina
authors.initials: N
authors.lastname: Smyth
authors.affiliation: Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge, CB2 0SR, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Barclay
authors.affiliation: Edinburgh Cancer Research Centre (IGMM), The University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XR, United Kingdom.
authors.forename: Marie
authors.initials: M
authors.lastname: Fallon
authors.affiliation: Cambridge University Hospitals NHS Foundation Trust, Palliative Care Department, Addenbrooke's Hospital, Hill's Road, Cambridge, CB2 0QQ, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Booth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm / Q000502:physiology*; D003430:Cross-Sectional Studies; D004417:Dyspnea / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012463:Saliva / Q000737:chemistry; D012890:Sleep / Q000502:physiology
chemical_list: D006854:Hydrocortisone
keywords: Breathlessness; Cortisol; Dyspnoea; Hypothalamic-pituitary-adrenal axis; Palliative care; Saliva