title: Biomarkers of oxidative stress following continuous positive airway pressure withdrawal: data from two randomised trials.
abstract: There is conflicting evidence whether intermittent hypoxia in obstructive sleep apnoea (OSA) influences oxidative stress. We hypothesised that withdrawal of continuous positive airway pressure (CPAP) from patients with OSA would raise markers of oxidative stress.59 patients with CPAP-treated moderate-to-severe OSA (oxygen desaturation index (ODI) >20 events·h(-1)) were randomised 1:1 to either stay on CPAP (n=30) or change to sham CPAP (n=29) for 2 weeks. Using samples from two similar studies at two sites, we measured early morning blood malondialdehyde (MDA, a primary outcome in one study and a secondary outcome in the other), lipid hydroperoxides, total antioxidant capacity, superoxide generation from mononuclear cells and urinary F2-isoprostane. We also measured superoxide dismutase as a marker of hypoxic preconditioning. "Treatment" effects (sham CPAP versus CPAP) were calculated via linear regression.Sham CPAP provoked moderate-to-severe OSA (mean ODI 46 events·h(-1)), but blood markers of oxidative stress did not change significantly (MDA "treatment" effect (95% CI) -0.02 (-0.23 to +0.19) μmol·L(-1)). Urinary F2-isoprostane fell significantly by ~30% (-0.26 (-0.42 to -0.10) ng·mL(-1)) and superoxide dismutase increased similarly (+0.17 (+0.02 to +0.30) ng·mL(-1)).We found no direct evidence of increased oxidative stress in patients experiencing a return of their moderate-to-severe OSA. The fall in urinary F2-isoprostane and rise in superoxide dismutase implies that hypoxic preconditioning may have reduced oxidative stress.
authors.affiliation: Oxford Centre for Respiratory Medicine and NIHR Oxford Biomedical Research Centre, Churchill Hospital Campus, Oxford University, Oxford, UK john.stradling@orh.nhs.uk.
authors.forename: John R
authors.initials: JR
authors.lastname: Stradling
authors.affiliation: Sleep Disorders Centre and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Esther I
authors.initials: EI
authors.lastname: Schwarz
authors.affiliation: Sleep Disorders Centre and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Schlatzer
authors.affiliation: Oxford Centre for Respiratory Medicine and NIHR Oxford Biomedical Research Centre, Churchill Hospital Campus, Oxford University, Oxford, UK.
authors.forename: Ari R
authors.initials: AR
authors.lastname: Manuel
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Campus, University of Oxford, Oxford, UK.
authors.forename: Regent
authors.initials: R
authors.lastname: Lee
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Campus, University of Oxford, Oxford, UK.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Antoniades
authors.affiliation: Sleep Disorders Centre and Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Kohler
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000737:chemistry; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D045422:Continuous Positive Airway Pressure; D028441:F2-Isoprostanes / Q000652:urine; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D000860:Hypoxia; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016014:Linear Models; D008055:Lipids / Q000737:chemistry; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D020181:Sleep Apnea, Obstructive / Q000097:blood / Q000503:physiopathology / Q000628:therapy* / Q000652:urine; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000097:blood; D055815:Young Adult
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D028441:F2-Isoprostanes; D008055:Lipids; D013481:Superoxides; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D010100:Oxygen