Pulmonary hypertension: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

Abstract

Pulmonary vascular dysfunction (PVD) precedes the onset of clinical signs and symptoms of pulmonary arterial hypertension (PAH). PAH is defined by the elevation of pulmonary arterial pressure, which often progresses to right ventricular (RV) dysfunction and failure. PAH affects subjects of all ages, and is associated with diverse medical conditions, most of which are rare. Several factors pose immediate challenges to the development of strategies for primary prevention of PAH, including: (1) the idiopathic or primary form of the disease is extremely rare, limiting screening practicality; (2) methods for the detection of preclinical PVD are currently not established; (3) the understanding of determinants of pulmonary vascular growth, structure, and function in normal and PAH states is insufficient; (4) relatively small numbers of "at-risk" subjects are available for long-term studies to accurately assess disease development; and (5) preventative therapies for PVD are lacking. Despite these limitations, leveraging known at-risk patient populations for study, as well as growing progress across multiple disciplines, ranging from systems biology to advanced and more sensitive functional imaging modalities, may facilitate the opportunity to significantly improve primary prevention research and implementation over the next decade.

Figure 1.

Due to the tremendous reserve of the pulmonary vasculature, resting pulmonary arterial hypertension (PAH) and symptoms occur long after the initial inciting events trigger pulmonary vascular dysfunction (PVD). Multiple known risk factors exist that can prompt the loss of normal pulmonary vessel function in utero and beyond. Risk factors are variable, including: (1) genetic (e.g., bone morphogenetic protein receptor type 2 [BMPR2] gene mutations and sickle cell lung disease); (2) environmental (e.g., dietary stimulants); and (3) endogenous (e.g., premature lung disease and portal hypertension). Resting pulmonary hypertension (PH) only occurs after an enormous proportion of the pulmonary vascular bed is lost, causing a rise in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). By the time a diagnosis of PH is made, PVD is far advanced. Ultimately, advanced right ventricular (RV) failure will occur. Primary prevention efforts must focus upon the detection and prevention of PVD, before the onset of PH.