Endothelin receptor antagonist and airway dysfunction in pulmonary arterial hypertension

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...

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Bibliographic Details
Published in:	Respiratory research Vol. 10; no. 1; p. 129
Main Authors:	Droste, Annette S, Rohde, David, Voelkers, Mirko, Filusch, Arthur, Bruckner, Thomas, Borst, Mathias M, Katus, Hugo A, Meyer, F Joachim
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 30-12-2009 BioMed Central BMC
Subjects:	Administration, Oral Airway management Airway obstruction (Medicine) Airway Obstruction - diagnosis Airway Obstruction - drug therapy Airway Obstruction - etiology Antihypertensive Agents - administration & dosage Autoimmune diseases Bosentan Complications and side effects Dosage and administration Drug therapy Endothelin Endothelin Receptor Antagonists Fees & charges Female HIV Hospitals Human immunodeficiency virus Humans Hypertension Hypertension, Pulmonary - complications Hypertension, Pulmonary - drug therapy Intubation Lungs Male Medical imaging Middle Aged Pulmonary arteries Pulmonary Artery Pulmonary hypertension Respiratory agents Respiratory function Risk factors Rodents Smooth muscle Standard deviation Statistical analysis Sulfonamides - administration & dosage Tomography Treatment Outcome Germany
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Summary:	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. 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). 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. 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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1465-993X 1465-9921 1465-993X 1465-9921
DOI:	10.1186/1465-9921-10-129