Speckle Tracking Echocardiography to Evaluate for Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease.

Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), increasing morbidity and mortality. Current echocardiographic measures have poor predictive value for the diagnosis of PH in COPD. Right ventricular (RV) strain obtained by speckle tracking echocardiography (STE) is a measure of myocardial deformation which correlates with RV function and survival in subjects with pulmonary arterial hypertension. We hypothesized that RV strain measurements would be feasible and correlate with invasive hemodynamic measurements in patients with COPD. Retrospective analysis of RV strain values from subjects with severe COPD with echocardiogram within 48 hours of right heart catheterization was performed. First, 54 subjects were included in the analysis. Right ventricular systolic pressure (RVSP) and RV strain could be estimated in 31% and 57%, respectively. Then, 61% had RV-focused apical views, and of those, RV strain could be obtained for 94%. RV free wall strain correlated with PVR (r = 0.41, p = 0.02). Subjects with pulmonary vascular resistance (PVR) > 3 Wood units (WU) had less negative (worse) RV free wall strain values than those with PVR ≤ 3 WU, with a median strain of -20 (-23, -12) versus -23 (-29, -15), p < 0.05. A receiver operating characteristic curve demonstrated an RV free wall strain of > -23 to be 92% sensitive and 44% specific for identifying PVR > 3 WU (AUC 0.71). RV strain estimates are feasible in the majority of subjects with severe COPD. RV strain correlates with PVR and may improve screening for PH in subjects with COPD.

Perioperative management of the patient with pulmonary hypertension.

Patients with pulmonary hypertension are at increased risk for perioperative morbidity and mortality. Elective surgery is generally discouraged in this patient population; however, there are times when surgery is deemed necessary. Currently, there are no guidelines for the preoperative risk assessment or perioperative management of subjects with pulmonary hypertension. The majority of the literature evaluating perioperative risk factors and mortality rates is observational and includes subjects with multiple etiologies of pulmonary hypertension. Subjects with pulmonary arterial hypertension, also referred to as World Health Organization group I pulmonary hypertension, and particularly those receiving pulmonary arterial hypertension-specific therapy may be at increased risk. Perioperative management of these patients requires a solid understanding and careful consideration of the hemodynamic effects of anesthetic agents, positive pressure ventilation and volume shifts associated with surgery in order to prevent acute right ventricular failure. We reviewed the most recent data regarding perioperative morbidity and mortality for subjects with pulmonary hypertension in an effort to better guide preoperative risk assessment and perioperative management by a multidisciplinary team.

Growth differentiation factor-15 and prognosis in acute respiratory distress syndrome: a retrospective cohort study.

INTRODUCTION: We sought to determine whether higher levels of the novel biomarker growth differentiation factor-15 (GDF-15) are associated with poor outcomes and the presence of pulmonary vascular dysfunction (PVD) in patients with acute respiratory distress syndrome (ARDS). METHODS: We conducted a retrospective cohort study in patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment (FACT) Trial. Patients enrolled in the FACT Trial who received a pulmonary artery catheter (PAC), had plasma available from the same study day and sufficient hemodynamic data to determine the presence of PVD were included. Logistic regression was used to determine the association between GDF-15 level and 60-day mortality. RESULTS: Of the 513 patients enrolled in the FACT Trial assigned to receive a PAC, 400 were included in this analysis. Mortality at 60 days was significantly higher in patients whose GDF-15 levels were in the third (28%) or fourth (49%) quartile when compared to patients with GDF-15 levels in the first quartile (12%) (P <0.001). Adjusting for severity of illness measured by APACHE III score, the odds of death for patients with GDF-15 levels in the fourth quartile when compared to the first quartile was 4.26 (95% CI 2.18, 10.92, P <0.001). When added to APACHE III alone for prediction of 60-day mortality, GDF-15 levels increased the area under the receiver operating characteristic curve from 0.72 to 0.77. At an optimal cutoff of 8,103 pg/mL, the sensitivity and specificity of GDF-15 for predicting 60-day mortality were 62% (95% CI 53%, 71%) and 76% (95% CI 71%, 81%), respectively. Levels of GDF-15 were not useful in identifying the presence of PVD, as defined by hemodynamic measurements obtained by a PAC. CONCLUSIONS: In patients with ARDS, higher levels of GDF-15 are significantly associated with poor outcome but not PVD.

Experiences with treprostinil in the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a chronic condition of elevated pulmonary arterial pressures with associated increases in pulmonary vascular resistance leading to right ventricular failure, which was almost uniformly fatal prior to the introduction of pulmonary hypertension specific therapy. Systemic prostacyclin analogs are the first PAH-specific therapies to be made available and are typically recommended as first-line therapy for subjects with severe disease. Treprostinil is a newer prostacyclin analog similar to epoprostenol in its mechanism of action and relative efficacy with the advantage of a longer half life in human serum and room temperature stability. It is unique in that it is available in multiple formulations for alternative routes of delivery, including subcutaneous, intravenous and inhalational routes. Additionally, oral treprostinil is currently under investigation. Both subcutaneous and intravenous forms of treprostinil have demonstrated efficacy in short-term clinical trials and are currently approved for use in subjects with PAH and New York Heart Association functional class (NYHA FC) II-IV symptoms in the USA and for subjects with NYHA FC III and IV in Europe. Inhaled treprostinil has also demonstrated efficacy in short-term clinical trials primarily as add-on therapy and is currently approved for use in subjects with PAH and NYHA FC III-IV symptoms in the USA and Europe. The different formulations of treprostinil have significantly increased the treatment options and opportunities for treatment of patients with PAH.

Cluster analysis of obesity and asthma phenotypes.

BACKGROUND: Asthma is a heterogeneous disease with variability among patients in characteristics such as lung function, symptoms and control, body weight, markers of inflammation, and responsiveness to glucocorticoids (GC). Cluster analysis of well-characterized cohorts can advance understanding of disease subgroups in asthma and point to unsuspected disease mechanisms. We utilized an hypothesis-free cluster analytical approach to define the contribution of obesity and related variables to asthma phenotype. METHODOLOGY AND PRINCIPAL FINDINGS: In a cohort of clinical trial participants (n = 250), minimum-variance hierarchical clustering was used to identify clinical and inflammatory biomarkers important in determining disease cluster membership in mild and moderate persistent asthmatics. In a subset of participants, GC sensitivity was assessed via expression of GC receptor alpha (GCRα) and induction of MAP kinase phosphatase-1 (MKP-1) expression by dexamethasone. Four asthma clusters were identified, with body mass index (BMI, kg/m(2)) and severity of asthma symptoms (AEQ score) the most significant determinants of cluster membership (F = 57.1, p<0.0001 and F = 44.8, p<0.0001, respectively). Two clusters were composed of predominantly obese individuals; these two obese asthma clusters differed from one another with regard to age of asthma onset, measures of asthma symptoms (AEQ) and control (ACQ), exhaled nitric oxide concentration (F(E)NO) and airway hyperresponsiveness (methacholine PC(20)) but were similar with regard to measures of lung function (FEV(1) (%) and FEV(1)/FVC), airway eosinophilia, IgE, leptin, adiponectin and C-reactive protein (hsCRP). Members of obese clusters demonstrated evidence of reduced expression of GCRα, a finding which was correlated with a reduced induction of MKP-1 expression by dexamethasone CONCLUSIONS AND SIGNIFICANCE: Obesity is an important determinant of asthma phenotype in adults. There is heterogeneity in expression of clinical and inflammatory biomarkers of asthma across obese individuals. Reduced expression of the dominant functional isoform of the GCR may mediate GC insensitivity in obese asthmatics.

Obesity and asthma disease phenotypes.

PURPOSE OF REVIEW: The increasing prevalence of both asthma and obesity is associated with substantial morbidity and healthcare utilization. Herein, we review recent data suggesting that the obese asthmatic may represent a distinct clinical phenotype. RECENT FINDINGS: Obesity is a major risk factor for asthma, and asthma in obese patients appears to be more difficult to control, with decreased responsiveness to controller therapies posing a significant public health issue, as the prevalence of both asthma and obesity continues to rise. Epidemiologic research has defined the association between obesity and asthma, an association in part influenced by physiologic abnormalities attendant to both disorders. Healthcare utilization is also increased in obese asthmatic individuals, with reduced response to asthma controller therapies, a finding likely mediated by specific aspects of systemic and airway inflammation. We end by reviewing the role of comorbid clinical disorders in the association and by highlighting evidence that weight loss is associated with improvement in clinical and physiologic parameters of asthma. SUMMARY: Obesity has a significant impact on asthma risk, severity and control. Additional studies are needed to define mechanisms by which airway physiologic and inflammatory phenotypes in asthma are modified by obesity.