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.

Pulmonary arterial hypertension: tailoring treatment to risk in the current era

“…The importance of regular risk assessment Achievement or maintenance of a low-risk status is reassuring; however, it is vital that physicians remain vigilant, as pathological changes within the pulmonary vasculature and RV can still occur even if no signs of clinical deterioration are apparent [19]. This has been illustrated in a study by VAN DE VEERDONK et al [20], which evaluated clinical, haemodynamic and RV changes in a cohort of patients who experienced disease progression resulting in death or lung transplantation after ⩾5 years of clinical stability.…”

“…As PAH is a progressive disease, there is a rationale for targeting all three pathogenic pathways immediately upon diagnosis with initial triple combination therapy in order to delay the remodelling of the pulmonary vasculature, which occurs even in the early stages of the disease [19]. At present, the benefits of initial triple oral combination therapy compared with initial dual oral combination therapy are unknown, but are the focus of the ongoing TRITON RCT [34].…”

Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction

“…PVD is often asymptomatic until severe, when approximately 50% to 70% of the pulmonary vascular bed is lost, both in structure and function, at which point pulmonary vascular resistance and pulmonary artery pressure rise, leading to a diagnosis of pulmonary hypertension (PH) or pulmonary artery hypertension (PAH) (17). Major risks for the development of PVD and PH include genetic mutation, environment (hypoxia, drugs), and immune deregulation and associated diseases (17,18). To date, the etiology of microvascular remodeling underlying PVD remains unknown and is complicated by a lack of rodent models recapitulating early-stage vasculopathy in the absence of or prior to injury.…”

Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity

“…Currently, premature birth is the leading cause of death in children under the age of 5 years, affecting 1 in 10 births and representing z15 million births per year worldwide (1)(2)(3)(4). In its most severe form, BPD can result in secondary cardiovascular sequelae such as pulmonary hypertension (PH) that persist into adulthood and abnormal ventilatory response (5)(6)(7)(8)(9)(10). Despite advances in clinical ventilator management, the introduction of surfactant, and antenatal glucocorticoids, there is a marked lack of adjunctive therapies.…”