Raed A. Dweik, MD
Director, Pulmonary Vascular Program
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 445-6542
Nitric oxide (NO) is endogenously synthesized by nitric oxide synthases (NOSs) which convert L-arginine to L-citrulline and NO in the presence of oxygen and several cofactors. Once produced, NO is freely diffusible and enters target cells and into the airway and can be detected in exhaled breath of all humans. NO is formed in high concentrations in the upper respiratory tract (nasopharynx and paranasal sinuses). Our studies have also conclusively demonstrated that the lower respiratory tract is a significant source of NO in exhaled breath. We have also demonstrated that endogenous NO levels in the lung change rapidly in direct proportion to inspired oxygen which strongly supports a critical role for NO as mediator of ventilation-perfusion coupling in the lung. NO also plays a major role in the pathophysiology of pulmonary hypertension (PH), a group of diseases characterized by high pulmonary artery pressures and pulmonary vascular resistance. Our studies have shown that patients with idiopathic pulmonary arterial hypertension (IPAH, previously known as primary pulmonary hypertension or PPH) have low levels of NO in their exhaled breath that increase after initiation of vasodilator therapy. The goal of our current studies is to understand the role of nitric oxide (and other markers in exhaled breath) in lung physiology and in the pathophysiology of lung diseases like pulmonary hypertension and asthma.
Dweik RA, et.al. NO synthesis in the lung. JCI 1998. Dweik RA, et.al. NO Chemical Events in the Human Airway During Antigen-Induced Asthmatic Response. PNAS 2001. Dweik RA. Pulmonary hypertension and the search for the selective pulmonary vasodilator. Lancet 2002.Dweik RA. Nitric oxide, hypoxia, and superoxide: the good, the bad, and the ugly! Thorax 2005.(Dweik RA, contributing author). ATS Recommendations for Standardized Procedures for Exhaled Nitric Oxide 2005. AJRCCM 2005.Dweik RA. The lung in the balance: arginine, methylated arginines, and nitric oxide. AJP Lung 2007.
Two training programs at Cleveland Clinic—the Supporting Multidisciplinary Achievement in Respiratory Research Training (SMARRT) Program and the Molecular Medicine PhD Program—have received significant new federal funding (called T32 grants) from the National Institutes of Health (NIH) to support students who are planning careers in those disciplines.
Pulmonary hypertension is considered the final common pathway of many varied diseases and syndromes, and therefore one cannot say it is idiopathic without making a robust effort to identify features of alternative causes and rule our other contributing factors. Akshay Bhatnegar, MD, staff in Department of Regional Anesthesiology, Raed Dweik, MD, Chair of the Respiratory Institute, and Neal Chaisson, MD, staff in the Departments of Pulmonary and Critical Care Medicine and the Respiratory Institute, authored an article published in the Cleveland Clinic Journal of Medicine which offers a case-based guide to evaluating patients with suspected pulmonary arterial hypertension (PAH).