title: Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension.
abstract: BACKGROUND
  In idiopathic pulmonary arterial hypertension (IPAH), peripheral airway obstruction is frequent. This is partially attributed to the mediator dysbalance, particularly an excess of endothelin-1 (ET-1), to increased pulmonary vascular and airway tonus and to local inflammation. Bosentan (ET-1 receptor antagonist) improves pulmonary hemodynamics, exercise limitation, and disease severity in IPAH. We hypothesized that bosentan might affect airway obstruction.
  
  
  METHODS
  In 32 IPAH-patients (19 female, WHO functional class II (n = 10), III (n = 22); (data presented as mean +/- standard deviation) pulmonary vascular resistance (11 +/- 5 Wood units), lung function, 6 minute walk test (6-MWT; 364 +/- 363.7 (range 179.0-627.0) m), systolic pulmonary artery pressure, sPAP, 79 +/- 19 mmHg), and NT-proBNP serum levels (1427 +/- 2162.7 (range 59.3-10342.0) ng/L) were measured at baseline, after 3 and 12 months of oral bosentan (125 mg twice per day).
  
  
  CONCLUSIONS
  At baseline, maximal expiratory flow at 50 and 25% vital capacity were reduced to 65 +/- 25 and 45 +/- 24% predicted. Total lung capacity was 95.6 +/- 12.5% predicted and residual volume was 109 +/- 21.4% predicted. During 3 and 12 months of treatment, 6-MWT increased by 32 +/- 19 and 53 +/- 69 m, respectively; p < 0.01; whereas sPAP decreased by 7 +/- 14 and 10 +/- 19 mmHg, respectively; p < 0.05. NT-proBNP serum levels tended to be reduced by 123 +/- 327 and by 529 +/- 1942 ng/L; p = 0.11). There was no difference in expiratory flows or lung volumes during 3 and 12 months.
  
  
  CONCLUSIONS
  This study gives first evidence in IPAH, that during long-term bosentan, improvement of hemodynamics, functional parameters or serum biomarker occur independently from persisting peripheral airway obstruction.
authors.affiliation: Department of Cardiology, Angiology and Respiratory Medicine, Heidelberg, Germany. an.dros@web.de
authors.forename: Annette S
authors.initials: AS
authors.lastname: Droste
authors.forename: David
authors.initials: D
authors.lastname: Rohde
authors.forename: Mirko
authors.initials: M
authors.lastname: Voelkers
authors.forename: Arthur
authors.initials: A
authors.lastname: Filusch
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.forename: Mathias M
authors.initials: MM
authors.lastname: Borst
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: F Joachim
authors.initials: FJ
authors.lastname: Meyer
mesh_terms: D000284:Administration, Oral; D000402:Airway Obstruction / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan