Pulmonary Arterial Hypertension

I am very happy to offer this issue of Seminars in Respiratory and Critical Care Medicine, which addresses important clinical and translational topics from leaders in the field of pulmonary arterial hypertension (PAH). I greatly appreciate the insight of Dr. Joseph Lynch, the editor in chief for Seminars, regarding the importance of this topic and for allowing me to be involved. The expert contributors have provided thoughtful, detailed, state-of-the-art reviews on their respective topics. Although 15 years ago there were no Food and Drug Administration (FDA)-approved medications for PAH, basic and clinical research in this area has increased exponentially and now oral, inhaled, and parenteral medications have been tested, proven, and approved. Understanding of genetic, pathogenetic, epidemiological, clinical, and therapeutic aspects of the disease have increased dramatically. These substantial advances have been welcomed by patients and clinicians alike.

In this issue, Drs. Perros, Dorfmüller, and Humbert from Paris present a superlative update on the pathogenesis of PAH. The process of pulmonary vascular remodeling involves all layers of the vessel wall, with each cell type (endothelial cells, smooth muscle cells, and fibroblasts), as well as inflammatory cells and platelets potentially playing a role in this condition. Dr. Gregory Elliott, from Salt Lake City, offers tremendous insight into the increasing knowledge base involving the genetic aspects of the disease. Scientists have learned the inheritance pattern as well as a major element of the molecular basis for inherited PAH. Mutations in the gene that codes for bone morphogenetic protein receptor type II (BMPR2), are a major predisposition for the development of PAH. Drs. Torbicki and Kurzyna, from Warsaw, Poland, review and emphasize the appropriate diagnostic approach to PAH and its importance in this disease. Without a detailed and methodical approach to the cause and severity of PAH, appropriate therapy cannot be offered. Dr. Oudiz, from Los Angeles, discusses how exercise testing for PAH can aid the clinician in outlining the nature of a patient's exercise limitation, noninvasively assessing disease severity, establishing prognosis, and evaluating the response to therapy. Dr. C. William Hargett and myself, in Durham, North Carolina, embrace the growing body of evidence that brain natriuretic peptide may be a potential biomarker for PAH in screening for occult disease, diagnostic evaluation, prognosis, and estimating a response to therapy.

Drs. Gomberg-Maitland, from Chicago, and Preston, from Boston, lead off the therapeutic discussion, emphasizing how prostacyclin therapy fits into the treatment armamentarium. Drs. Lee and Channick, from San Diego, then discuss the importance of endothelin in the pathogenesis of PAH. Substantial evidence from clinical trials and long-term data with endothelin receptor antagonists indicate their beneficial, therapeutic nature in PAH. Dr. Murali Chakinala, from St. Louis, explores the impact of available therapies on prognosis in PAH, which ultimately rests on the ability to reverse pulmonary arteriopathy and preserve right ventricular function. Drs. Olsson, Zamanian, Feinstein, and Doyle from Stanford offer a comprehensive review of the surgical options for patients with pulmonary hypertension, emphasizing pulmonary thromboendarterectomy for pulmonary hypertension associated with chronic thromboembolic disease, closure of congenital systemic-pulmonary shunts in patients with PAH but without significant pulmonary vascular disease, and the option of lung transplantation in patients who demonstrate advanced or progressive disease. Finally, Dr. Todd Bull, from Denver, offers an in-depth discussion on novel PAH therapies in the context of recent clinical trials, as well as examining the data available for the role of combination therapy in the treatment of PAH. He also speculates on new therapeutic directions for the management of this life-threatening disease.

I believe that the combined efforts of our contributors have led to an expert, well-balanced, and comprehensive state-of-the-art treatise on PAH. I hope that our readers will find these reviews useful in their practices, with the ultimate goal of the best possible patient care.