Pulmonary Hypertension

Clinical/Translational Research Translational-Clinical Research

Pulmonary Hypertension
Pulmonary hypertension is a complex disorder with significant effects on morbidity and mortality. It is of paramount importance to gain greater understanding of the mechanisms responsible for disease pathogenesis in these patients to provide more comprehensive treatment options. The mission of the Pulmonary Hypertension Center at Boston Medical Center (Boston University School of Medicine) is to improve the lives of persons living with pulmonary hypertension by providing state-of-the-art patient care coupled with innovative research aimed at understanding the pathogenesis and natural history of pulmonary hypertension. This center is the clinical repository for ongoing basic science, translational, and clinical studies on pulmonary hypertension. Our research group interacts with our clinical Pulmonary Hypertension Center in a highly integrated approach to advancing knowledge and treatment of this disease.

Background:
Pulmonary hypertension (PH), defined as a mean pulmonary artery pressure of >25 mm Hg at rest, a PCWP or LVEDP <15, and PVR > 240 dynes/cm-5 (3 Wood units), can occur rarely in isolation [idiopathic pulmonary arterial hypertension (IPAH)] but much more commonly in association with other disease entities such as connective tissue diseases, HIV infection, portal hypertension and hemoglobinopathies. Little is known regarding the pathogenesis of these disorders. As many share similar histologies, it is possible that common pathophysiologic mechanisms link these disorders. The goal of our research group is to establish patient cohorts with different forms of PH to study clinically and pathologically. Clinical projects within the group focus on disease outcomes, treatment and prognosis. Basic science and translational research projects focus on the use of genetic resources and biomarkers to identify novel molecules for further investigation.

Current research projects and clinical trials in our center include:

  • Gene polymorphisms in sickle cell associated pulmonary hypertension (see sickle cell website)
  • Role of oxidative post-translational protein modifications in PH of sickle cell lung disease (see sickle cell website)
  • Association of specific genetic modulations in the pathogenesis of PH associated with systemic sclerosis
  • Study of pulmonary hypertension associated with left ventricular diastolic dysfunction using patients from the Pulmonary Hypertension Center and Cardiomyopathy Program at Boston Medical Center (developing the genotype and the phenotype of these patients; and examining new treatments in this entity)
  • ARIES 3 – Use of ambrisentan in the treatment of Pulmonary Hypertension
  • Assessment of cicletanine in patients with PAH
  • Assessment of masitentan in patients with PAH (Seraphin trials)
  • Assessment of AC-065A301 in patients with PAH (Griphon trials)
  • Dose response trial of ambrisentan in patients with PAH secondary to scleroderma
  • Incidence of pulmonary hypertension in patients with scleroderma (DETECT trials)

Principal Investigators:
Harrison W. Farber, MD
Elizabeth S. Klings, MD
Robert Simms, MD, Section of Rheumatology
Robert Lafyatis, Section of Rheumatology
Flora Sam, MD, Section of Cardiology

Post-Doctoral Fellows:

Research Coordinators:
Fei-Ying Cheong
Kim Tobin
Cindy Garcia

Links:

Selected Publications:

  1. Ieong MH, Farber HW.  Non-infectious pulmonary complications of HIV infection Clin Pulm Med 2006; 13:194-202.
  2. Tam DH, Farber HW. Pulmonary hypertension and β-thalassemia major: Report of a case, its treatment, and a review of the literature.  Am J Hematol 2006; 81:443-447.
  3. Fisher KA, Serlin DM, Wilson KC, Walter RE, Farber HW.  Sarcoidosis associated pulmonary hypertension: Outcome with long-term epoprostenol treatment.  Chest 2006; 130: 1481-1488.
  4. Patterson KC, Weissmann A, Ahmadi T, Farber HW. Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension.  Ann Intern Med 2006; 145:152-153.
  5. Steiner MK, Preston IR, Klinger JR, Criner GJ, Waxman AB, Farber HW, Hill NS.  Conversion to bosentan from prostacyclin infusion therapy in pulmonary arterial hypertension: A pilot study.  Chest 2006;130:1471-1480
  6. Klings ES, Bland DA, Rosenman D, Princeton S, Odhiambo A, Li G, Bernard SA,. Steinberg MA, Farber HW. Pulmonary arterial hypertension and left-sided heart disease in sickle cell disease: Clinical characteristics and association with soluble adhesion molecule expression. Am J Hematol 2008; 83:547-553.
  7. Distler O, Behrens F, Pittrow D, and the EPOSS-Omeract Group. Defining appropriate outcome measures in pulmonary arterial hypertension related to systemic sclerosis: A Delphi consensus study with cluster analysis. Arthritis Care & Research 2008; 59: 867-875.
  8. McGoon M, Krichman AM, Farber HW, Barst RJ, Raskob G, Liou TG, Miller DP, Feldkircher K, Giles S. Design of the REVEAL registry for US patients with pulmonary arterial hypertension. Mayo Clin Proc 2008; 83:923-931.
  9. Farber HW. The status of pulmonary arterial hypertension in 2008. Circulation 2008; 117:2996-2998.
  10. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS,. Rubin LJ, Tapson VF, Varga J. ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension. Circulation 2009; 119:2250-2294

Primary teaching affiliate
of BU School of Medicine