An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease.

Background: In adults with sickle cell disease (SCD), an increased tricuspid regurgitant velocity (TRV) measured by Doppler echocardiography, an increased serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, and pulmonary hypertension (PH) diagnosed by right heart catheterization (RHC) are independent risk factors for mortality.

Methods: A multidisciplinary committee was formed by clinician-investigators experienced in the management of patients with PH and/or SCD. Clinically important questions were posed, related evidence was appraised, and questions were answered with evidence-based recommendations.

Diminazene attenuates pulmonary hypertension and improves angiogenic progenitor cell functions in experimental models.

Rationale: Studies have demonstrated that angiotensin-converting enzyme 2 (ACE2) plays a protective role against lung diseases, including pulmonary hypertension (PH). Recently, an antitrypanosomal drug, diminazene aceturate (DIZE), was shown to exert an "off-target" effect of enhancing the enzymatic activity of ACE2 in vitro.

Objectives: To evaluate the pharmacological actions of DIZE in experimental models of PH.

Hypoxia-induced endothelial CX3CL1 triggers lung smooth muscle cell phenotypic switching and proliferative expansion.

Distal arterioles with limited smooth muscles help maintain the high blood flow and low pressure in the lung circulation. Chronic hypoxia induces lung distal vessel muscularization. However, the molecular events that trigger alveolar hypoxia-induced peripheral endothelium modulation of vessel wall smooth muscle cell (SMC) proliferation and filling of nonmuscular areas are unclear.

Pulmonary arterial hypertension: classification and therapy with a focus on prostaglandin analogs.

Pulmonary arterial hypertension, part of the larger spectrum of disorders causing pulmonary hypertension, is a complex and progressive disease of multiple etiologies that ultimately leads to vascular remodeling, right-sided heart failure, and death. Advances in treatment over the past 15 to 20 years have dramatically reduced the morbidity and mortality of the disease, but often have significant drawbacks. Of the more recently approved therapies, the prostaglandin analogs have been shown to have the greatest therapeutic benefit but are also the most difficult to administer, many being given as continuous intravenous infusions in the ambulatory setting.

Value of impedance cardiography in patients studied for pulmonary hypertension.

The aim of this study was to evaluate the accuracy and precision of impedance cardiography as a method for noninvasive hemodynamic evaluation of patients with pulmonary hypertension (PH). We performed a prospective and blinded study of patients who underwent right heart catheterization (RHC) for evaluation of known or presumed PH at the University of Florida from August 2009 to March 2010. The cohort consisted of a total of 39 patients (age = 57 ± 14 years, 87% women) with presumed (23%) or confirmed PH (77%) of different etiologies.

Effect of balloon inflation volume on pulmonary artery occlusion pressure in patients with and without pulmonary hypertension.

Background: Pulmonary artery occlusion pressure (PAOP) is used to differentiate patients with pulmonary hypertension (PH) associated with left-sided heart disease from other etiologies. Technical errors in the measurement of PAOP are common and lead to incorrect classification of the etiology of PH. We investigated the agreement among PAOP measurements obtained from both pulmonary arteries with balloon full (1.

Prevalence of pulmonary hypertension in end-stage cystic fibrosis and correlation with survival.

Background: Limited information is available about the prevalence of pulmonary hypertension diagnosed by right heart catheterization (RHC) in patients with cystic fibrosis being evaluated for lung transplantation. It is unclear whether there are factors that can predict the presence of pulmonary hypertension and whether the presence of pulmonary hypertension influences patient outcomes.

Methods: The study included 57 unique and consecutive adult patients (33 women) with cystic fibrosis who underwent lung transplant evaluation at the University of Florida.

Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies.

Doppler-defined pulmonary hypertension (PH) in sickle cell disease (SCD) is associated with 40% mortality at 40 months. To assess the effect of bosentan in SCD-PH, two randomized, double-blind, placebo-controlled, 16-week studies were initiated. Safety concerns are particularly relevant in SCD due to comorbid conditions.

Pulmonary vasodilator testing and use of calcium channel blockers in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) encompasses a number of diseases responsible for a specific set of hemodynamic findings during right heart catheterization. During initial workup, pulmonary vasodilator testing is performed. A positive acute pulmonary vasodilator test predicts better survival and response to calcium channel blocker (CCB) therapy.

A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension is a chronic, progressive disease characterized by elevation of pulmonary artery pressure and pulmonary vascular resistance that ultimately results in right ventricular failure and death. Multiple mechanisms are involved in the pathogenesis of pulmonary arterial hypertension, including prostacyclin, endothelin-1, and nitric oxide pathways amongst others. The first agent to be approved for the treatment of pulmonary arterial hypertension was synthetic prostacyclin (epoprostenol), followed by prostaglandin analogs (iloprost, treprostinil, and beraprost [Japan and Korea]), which act on prostaglandin receptors.

Pleural mesothelial cell transformation into myofibroblasts and haptotactic migration in response to TGF-beta1 in vitro.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis noted in the pulmonary parenchyma. Pleural mesothelial cells (PMC) are metabolically dynamic cells that cover the lung and chest wall as a monolayer and are in intimate proximity to the underlying lung parenchyma. The precise role of PMC in the pathogenesis of pulmonary parenchymal fibrosis remains to be identified.

Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease.

Rationale: The Scleroderma Lung Study enrolled 158 patients with scleroderma-related interstitial lung disease in a placebo-controlled trial of oral cyclophosphamide (CYC). Although treatment-related benefits in pulmonary function, skin scores, and patient-centered outcomes were demonstrated after 1 year of therapy, the duration of benefit beyond 1 year was unclear.

Objectives: A second year of follow-up was performed to determine if these effects persisted after stopping treatment.

Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: results from the scleroderma lung study.

Objective: To assess the impact of cyclophosphamide (CYC) on the health-related quality of life (HRQOL) of patients with scleroderma after 12 months of treatment.

Methods: One hundred fifty-eight subjects participated in the Scleroderma Lung Study, with 79 each randomized to CYC and placebo arms. The study evaluated the results of 3 measures of health status: the Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ) disability index (DI), and Mahler's dyspnea index, and the results of 1 preference-based measure, the SF-6D.

Cyclophosphamide versus placebo in scleroderma lung disease.

Background: We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease.

Methods: At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic high-resolution computed tomography, or both. Patients received oral cyclophosphamide (< or =2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year.

Correlation of the degree of dyspnea with health-related quality of life, functional abilities, and diffusing capacity for carbon monoxide in patients with systemic sclerosis and active alveolitis: results from the Scleroderma Lung Study.

Objective: To determine whether baseline self-assessment measures of health status and physiologic indices of disease severity in alveolitis-positive patients with systemic sclerosis (SSc) correlate with the severity of their dyspnea, and to quantify functional impairment in patients with scleroderma lung disease and compare it with that in patients with chronic obstructive pulmonary disease (COPD).

Methods: SSc patients (n = 138) with diffuse (n = 81) or limited (n = 57) cutaneous disease and active alveolitis (determined by bronchoalveolar lavage and/or high-resolution computed tomography) who participated in the National Heart, Lung, and Blood Institute-sponsored, multicenter, parallel-group, double-blind, randomized, placebo-controlled trial of oral cyclophosphamide for treatment of SSc-associated interstitial lung disease were evaluated. Pearson's univariate correlations were determined between the Short Form 36 (SF-36) physical component summary (PCS) and mental component summary (MCS) scales, functional questionnaires, and physiologic parameters of breathing (forced vital capacity [FVC] and single-breath diffusing capacity for carbon monoxide [DLCO]).