title: Quantifying the ventilatory control contribution to sleep apnoea using polysomnography.
abstract: Elevated loop gain, consequent to hypersensitive ventilatory control, is a primary nonanatomical cause of obstructive sleep apnoea (OSA) but it is not possible to quantify this in the clinic. Here we provide a novel method to estimate loop gain in OSA patients using routine clinical polysomnography alone. We use the concept that spontaneous ventilatory fluctuations due to apnoeas/hypopnoeas (disturbance) result in opposing changes in ventilatory drive (response) as determined by loop gain (response/disturbance). Fitting a simple ventilatory control model (including chemical and arousal contributions to ventilatory drive) to the ventilatory pattern of OSA reveals the underlying loop gain. Following mathematical-model validation, we critically tested our method in patients with OSA by comparison with a standard (continuous positive airway pressure (CPAP) drop method), and by assessing its ability to detect the known reduction in loop gain with oxygen and acetazolamide. Our method quantified loop gain from baseline polysomnography (correlation versus CPAP-estimated loop gain: n=28; r=0.63, p<0.001), detected the known reduction in loop gain with oxygen (n=11; mean±sem change in loop gain (ΔLG) -0.23±0.08, p=0.02) and acetazolamide (n=11; ΔLG -0.20±0.06, p=0.005), and predicted the OSA response to loop gain-lowering therapy. We validated a means to quantify the ventilatory control contribution to OSA pathogenesis using clinical polysomnography, enabling identification of likely responders to therapies targeting ventilatory control.
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia.
authors.forename: Philip I
authors.initials: PI
authors.lastname: Terrill
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Edwards
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Shamim
authors.initials: S
authors.lastname: Nemati
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Owens
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Neuroscience Research Australia and the School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eckert
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: White
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care, University of Southern California San Diego, La Jolla, CA, USA.
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wellman
authors.affiliation: Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA Central Clinical School, The Alfred and Monash University, Melbourne, Australia sasands@partners.org.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sands
mesh_terms: D000086:Acetazolamide; D000328:Adult; D003198:Computer Simulation; D045422:Continuous Positive Airway Pressure; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009991:Oscillometry; D010100:Oxygen; D010349:Patient Compliance; D010641:Phenotype; D017286:Polysomnography; D012119:Respiration; D012189:Retrospective Studies; D012890:Sleep; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis* / Q000503:physiopathology*
chemical_list: D000086:Acetazolamide; D010100:Oxygen