Appelenglish2019

While there has been a longstanding interest in metabolic disease in pulmonary hypertension, publications in the last several years have translated basic science findings to human disease and even led to recently published studies of metabolic therapy in pulmonary arterial hypertension that are discussed here.

Progress has been made in four key areas including mechanisms of insulin resistance in pulmonary arterial hypertension, the role of obesity in pulmonary vascular disease, novel clinical trials targeting metabolism in pulmonary hypertension, and the role of metabolism in chronic thromboembolic pulmonary hypertension.

Insulin resistance in pulmonary arterial hypertension is primarily in the lipid axis. There are systemic manifestations of insulin resistance including right ventricular lipotoxicity. Obesity is associated with elevation of right ventricular systolic pressure even in a healthy population and therapies in pulmonary arterial hypertension that target metabolism hold promise for improving exercise, right ventricular function, and visceral adiposity. Finally, there are emerging data that chronic thromboembolic pulmonary hypertension is similarly characterized by metabolic alterations, though the specific metabolites may be different from pulmonary arterial hypertension.

Insulin resistance in pulmonary arterial hypertension is primarily in the lipid axis. There are systemic manifestations of insulin resistance including right ventricular lipotoxicity. Obesity is associated with elevation of right ventricular systolic pressure even in a healthy population and therapies in pulmonary arterial hypertension that target metabolism hold promise for improving exercise, right ventricular function, and visceral adiposity. Finally, there are emerging data that chronic thromboembolic pulmonary hypertension is similarly characterized by metabolic alterations, though the specific metabolites may be different from pulmonary arterial hypertension.

We review the clinical manifestations of three less common connective tissue disease (CTD)-associated interstitial lung diseases (ILDs) Sjogren's syndrome (SjS), mixed CTD (MCTD), and systemic lupus erythematosus (SLE).

SjS is classically associated with lymphocytic interstitial pneumonia and cystic lung disease, but the most common type of ILD in Sjogren's patients is nonspecific interstitial pneumonia. ILD is prevalent in MCTD and associated with worse survival. SLE-associated ILD, while rare, is more common in those with CTD overlap syndromes. Regardless of underlying cause, a subset of patients with fibrotic CTD-associated ILD develop a progressive course for which antifibrotic agents and lung transplantation should be considered.

An understanding of the characteristics of ILD in SjS, MCTD, and SLE is important for the pulmonary specialist. Future research should identify risk factors for progression and develop additional treatment modalities for both CTD-related autoimmune features and progressive ILD.

An understanding of the characteristics of ILD in SjS, MCTD, and SLE is important for the pulmonary specialist. Future research should identify risk factors for progression and develop additional treatment modalities for both CTD-related autoimmune features and progressive ILD.

Pulmonary vascular disease resulting in pulmonary hypertension in the context of interstitial lung disease (PH-ILD) is a common complication that presents many challenges in clinical practice. Despite recent advances, the pathogenetic interplay between parenchymal and vascular disease in ILD is not fully understood. This review provides an overview of the current knowledge and recent advances in the field.

Clinical trials employing the phosphodiesterase-5-inhibitor sildenafil delivered negative results whereas riociguat showed harmful effects in the PH-ILD population. More recently, inhaled treprostinil showed positive effects on the primary endpoint (six-min walk-distance) in the largest prospective randomized placebo-controlled trial to date in this patient population. Guanosine 5'-triphosphate mouse Additionally, a pilot trial of ambulatory inhaled nitric oxide suggests beneficial effects based on the novel endpoint of actigraphy.

In view of these novel developments this review provides an overview of the status quo of screening, diagnosis and management of pulmonary vascular disease and PH in patients with ILD.

In view of these novel developments this review provides an overview of the status quo of screening, diagnosis and management of pulmonary vascular disease and PH in patients with ILD.

It is now recognized that more than half of patients with acute pulmonary embolism (APE) will have persistent symptoms beyond 3 months after their initial event. Persistent symptoms are referred to as post-PE syndrome, an umbrella term that covers a spectrum of patient complaints and underlying pathologies. Data published over the last 5 years have added significantly to our understanding of this syndrome and its management.

Underlying pathologies linked to post-PE syndrome include chronic thromboembolic pulmonary hypertension (CTEPH), chronic thromboembolic disease (CTED), cardiac dysfunction, and deconditioning. Treatment for post-PE syndrome will depend on the underlying causative pathologies found. Evaluation and treatment for CTEPH is well defined, but less than 10% of patients with post-PE syndrome will qualify as having this diagnosis.

A large percentage of patients will experience post-PE syndrome following APE. Strategies for identification and treatment for some pathologies are well studied, but the majority of patients will have subtle abnormalities on imaging and functional testing for which diagnostic criteria and management are not well defined. A number of active studies are designed to help optimize the management of post-PE syndrome and should help us improve intermediate and long-term outcomes for patients following APE.

A large percentage of patients will experience post-PE syndrome following APE. Strategies for identification and treatment for some pathologies are well studied, but the majority of patients will have subtle abnormalities on imaging and functional testing for which diagnostic criteria and management are not well defined. A number of active studies are designed to help optimize the management of post-PE syndrome and should help us improve intermediate and long-term outcomes for patients following APE.