title: Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized, double-blind, cross-over trial.
abstract: OBJECTIVE
  Sleep-disturbed breathing (SDB) is common in pre-capillary pulmonary hypertension (PH) and impairs daytime performance. In lack of proven effective treatments, we tested whether nocturnal oxygen therapy (NOT) or acetazolamide improve exercise performance and quality of life in patients with pre-capillary PH and SDB.
  
  
  METHODS
  This was a randomized, placebo-controlled, double-blind, three period cross-over trial. Participants received NOT (3 L/min), acetazolamide tablets (2 × 250 mg), and sham-NOT/placebo tablets each during 1 week with 1-week washout between treatment periods. Twenty-three patients, 16 with pulmonary arterial PH, 7 with chronic thromboembolic PH, and with SDB defined as mean nocturnal oxygen saturation <90% or oxygen saturation dips >10 h(-1) with daytime PaO2 ≥7.3 kPa participated. Assessments at the end of the treatment periods included a 6 min walk distance (MWD), SF-36 quality of life, polysomnography, and echocardiography.
  
  
  RESULTS
  Medians (quartiles) of the 6 MWD after NOT, acetazolamide, and placebo were 480 m (390;528), 440 m (368;468), and 454 m (367;510), respectively, mean differences: NOT vs. placebo +25 m (95% CI 3-46, P= 0.027), acetazolamide vs. placebo -9 m (-34-17, P = 0.223), and NOT vs. acetazolamide +33 (12-45, P < 0.001). SF-36 quality of life was similar with all treatments. Nocturnal oxygen saturation significantly improved with both NOT and acetazolamide. Right ventricular fractional area change was greater on NOT compared with placebo (P = 0.042) and acetazolamide (P = 0.027).
  
  
  CONCLUSIONS
  In patients with pre-capillary PH and SDB on optimized pharmacological therapy, NOT improved the 6 MWD compared with placebo already after 1 week along with improvements in SDB and haemodynamics.
  
  
  BACKGROUND
  NTC01427192.
authors.affiliation: Pulmonary Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland silvia.ulrich@usz.ch.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ulrich
authors.affiliation: Pulmonary Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Keusch
authors.affiliation: Pulmonary Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Florian F
authors.initials: FF
authors.lastname: Hildenbrand
authors.affiliation: Pulmonary Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Lo Cascio
authors.affiliation: Pulmonary Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Huber
authors.affiliation: Cardiology Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Felix C
authors.initials: FC
authors.lastname: Tanner
authors.affiliation: Clinic of Internal Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Speich
authors.affiliation: Pulmonary Clinic, Department of Cardiovascular and Thoracic Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
authors.forename: Konrad E
authors.initials: KE
authors.lastname: Bloch
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy / Q000379:methods; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000628:therapy*; D000860:Hypoxia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000008:administration & dosage*; D012891:Sleep Apnea Syndromes / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D000086:Acetazolamide; D010100:Oxygen
keywords: Hypertension; Hypoxia; Pulmonary; Pulmonary heart disease; Sleep