title: Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: a prospective, multicentre, randomised, controlled clinical trial.
abstract: BACKGROUND
  Evidence is weak for the ability of long-term non-invasive positive pressure ventilation (NPPV) to improve survival in patients with stable hypercapnic chronic obstructive pulmonary disease (COPD). Previous prospective studies did not target a reduction in hypercapnia when adjusting ventilator settings. This study investigated the effect of long-term NPPV, targeted to markedly reduce hypercapnia, on survival in patients with advanced, stable hypercapnic COPD.
  
  
  METHODS
  This investigator-initiated, prospective, multicentre, randomised, controlled clinical trial enrolled patients with stable GOLD stage IV COPD and a partial carbon dioxide pressure (PaCO2) of 7 kPa (51.9 mm Hg) or higher and pH higher than 7.35. NPPV was targeted to reduce baseline PaCO2 by at least 20% or to achieve PaCO2 values lower than 6.5 kPa (48.1 mm Hg). Patients were randomly assigned (in a 1:1 ratio) via a computer-generated randomisation sequence with a block size of four, to continue optimised standard treatment (control group) or to receive additional NPPV for at least 12 months (intervention group). The primary outcome was 1-year all-cause mortality. Analysis was by intention to treat. The intervention was unblinded, but outcome assessment was blinded to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT00710541.
  
  
  RESULTS
  Patients were recruited from 36 respiratory units in Germany and Austria, starting on Oct 29, 2004, and terminated with a record of the vital status on July 31, 2011. 195 patients were randomly assigned to the NPPV group (n=102) or to the control group (n=93). All patients from the control group and the NPPV group were included in the primary analysis. 1-year mortality was 12% (12 of 102 patients) in the intervention group and 33% (31 of 93 patients) in the control group; hazard ratio 0.24 (95% CI 0.11-0.49; p=0.0004). 14 (14%) patients reported facial skin rash, which could be managed by changing the type of the mask. No other intervention-related adverse events were reported.
  
  
  CONCLUSIONS
  The addition of long-term NPPV to standard treatment improves survival of patients with hypercapnic, stable COPD when NPPV is targeted to greatly reduce hypercapnia.
  
  
  BACKGROUND
  German Lung Foundation; ResMed, Germany; Tyco Healthcare, Germany; and Weinmann, Germany.
authors: From the Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany. Electronic address: koehnlein.thomas@mh-hannover.de.
authors: Thomas
authors: T
authors: Köhnlein
authors: Centre for Respiratory Medicine, Hospital Köln-Merheim, University of Witten/Herdecke, Cologne, Germany.
authors: Wolfram
authors: W
authors: Windisch
authors: Department of Pneumology I, Fachkrankenhaus Kloster Grafschaft, Schmallenberg, Germany.
authors: Dieter
authors: D
authors: Köhler
authors: Department of Medical Biometry and Epidemiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Anna
authors: A
authors: Drabik
authors: Centre of Pneumology and Thoracic Surgery, Asklepios Hospital Gauting, Department of Intensive Care Medicine and Long-term Ventilation, Gauting, Germany.
authors: Jens
authors: J
authors: Geiseler
authors: Department of Respiratory and Critical Care Medicine, and Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria.
authors: Sylvia
authors: S
authors: Hartl
authors: Centre of Pneumology and Thoracic Surgery, Asklepios Hospital Gauting, Department of Intensive Care Medicine and Long-term Ventilation, Gauting, Germany.
authors: Ortrud
authors: O
authors: Karg
authors: Department of Respiratory Medicine, Evangelisches Klinikum Niederrhein, Oberhausen, Germany.
authors: Gerhard
authors: G
authors: Laier-Groeneveld
authors: Department of Specialist, Diagnostic, and Experimental Medicine, School of Medicine, Università di Bologna, Bologna, Italy.
authors: Stefano
authors: S
authors: Nava
authors: Department of Respiratory Medicine, Klinikum Oststadt-Heidehaus, Hannover, Germany.
authors: Bernd
authors: B
authors: Schönhofer
authors: LungenClinic Grosshansdorf, Center for Pneumology and Thoracic Surgery, Grosshansdorf, Germany.
authors: Bernd
authors: B
authors: Schucher
authors: Department of Medical Biometry and Epidemiology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Karl
authors: K
authors: Wegscheider
authors: Department of Pneumology, Respiratory Care, and Sleep Medicine, Evangelisches Krankenhaus Göttingen-Weende, Bovenden-Lenglern, Germany.
authors: Carl P
authors: CP
authors: Criée
authors: Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; Member of the German Centre for Lung Research.
authors: Tobias
authors: T
authors: Welte
mesh_terms: D000368:Aged; D001317:Austria; D001785:Blood Gas Monitoring, Transcutaneous; D005260:Female; D005858:Germany; D006801:Humans; D006935:Hypercapnia / Q000097:blood / Q000628:therapy; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D063087:Noninvasive Ventilation / Q000379:methods*; D011175:Positive-Pressure Respiration / Q000379:methods*; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000401:mortality* / Q000628:therapy*; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome