Defining Transplantation and Listing Benefit in Patients with Chronic Obstructive Pulmonary Disease

Invited Editorialhttp://deepblue.lib.umich.edu/bitstream/2027.42/91967/1/2008 AJRCCM Defining Transplantation and Listing Benefit in Patients with Chronic Obstructive Pulmonary Disease.pd

Adipokines and the Right Ventricle: The MESA-RV Study.

ObjectiveObesity is associated with changes in both right (RV) and left (LV) ventricular morphology, but the biological basis of this finding is not well established. We examined whether adipokine levels were associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.MethodsWe examined relationships of leptin, resistin, TNF-α, and adiponectin with RV morphology and function (from cardiac MRI) in participants (n = 1,267) free of clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA)-RV study. Multivariable regressions (linear, quantile [25th and 75th] and generalized additive models [GAM]) were used to examine the independent association of each adipokine with RV mass, RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV) and RV ejection fraction (RVEF).ResultsHigher leptin levels were associated with significantly lower levels of RV mass, RVEDV, RVESV and stroke volume, but not RVEF, after adjustment for age, gender, race, height and weight. These associations were somewhat attenuated but still significant after adjustment for traditional risk factors and covariates, and were completely attenuated when correcting for the respective LV measures. There were no significant interactions of age, gender, or race/ethnicity on the relationship between the four adipokines and RV structure or function.ConclusionsLeptin levels are associated with favorable RV morphology in a multi-ethnic population free of cardiovascular disease, however these associations may be explained by a yet to be understood bi-ventricular process as this association was no longer present after adjustment for LV values. These findings complement the associations previously shown between adipokines and LV structure and function in both healthy and diseased patients. The mechanisms linking adipokines to healthy cardiovascular function require further investigation

Intravenous Immunoglobulin for Hypogammaglobulinemia after Lung Transplantation: A Randomized Crossover Trial

Background We aimed to determine the effects of treatment with intravenous immunoglobulin on bacterial infections in patients with hypogammaglobulinemia (HGG) after lung transplantation. Methods We performed a randomized, double-blind, placebo-controlled two-period crossover trial of immune globulin intravenous (IVIG), 10% Purified (Gamunex, Bayer, Elkhart, IN) monthly in eleven adults who had undergone lung transplantation more than three months previously. We randomized study participants to three doses of IVIG (or 0.1% albumin solution (placebo)) given four weeks apart followed by a twelve week washout and then three doses of placebo (or IVIG). The primary outcome was the number of bacterial infections within each treatment period. Results IVIG had no effect on the number of bacterial infections during the treatment period (3 during IVIG and 1 during placebo; odds ratio 3.5, 95% confidence interval 0.4 to 27.6, p = 0.24). There were no effects on other infections, use of antibiotics, or lung function. IVIG significantly increased trough IgG levels at all time points (least square means, 765.3 mg/dl during IVIG and 486.3 mg/dl during placebo, p<0.001). Four serious adverse events (resulting in hospitalization) occurred during the treatment periods (3 during active treatment and 1 during the placebo period, p = 0.37). Chills, flushing, and nausea occurred during one infusion of IVIG. Conclusions Treatment with IVIG did not reduce the short-term risk of bacterial infection in patients with HGG after lung transplantation. The clinical efficacy of immunoglobulin supplementation in HGG related to lung transplantation over the long term or with recurrent infections is unknown

Pulmonary artery stiffness in chronic obstructive pulmonary disease (copd) and emphysema: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study

Purpose: Chronic obstructive pulmonary disease (COPD) and particularly emphysema are characterized by stiffness of the aorta, due in part to accelerated elastin degradation in the lungs and aorta. Stiffness of the pulmonary arteries (PAs) may also be increased in COPD and emphysema, but data are lacking. We assessed PA stiffness using MRI in patients with COPD and related these measurements to COPD severity and percent emphysema. Materials and Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited 290 participants, age 50–79 years with 10 or more packyears and free of clinical cardiovascular disease. COPD severity were defined on postbronchodilator spirometry by ATS/ERS criteria. Percent emphysema was defined as the percentage of regions of the lung &lt; -950 Hounsfield units on full-lung computed tomography (CT). PA stain was defined by the percent change in cross-sectional PA area between systole and diastole on MRI. Blood flow across the tricuspid and mitral valves was assessed by phase-contrast MRI for determination of the ventricular diastolic dysfunction (E/A ratio). Results: PA strain was reduced in COPD compared with controls (P = 0.002) and was inversely correlated with COPD severity (P = 0.004). PA strain was inversely associated to percent emphysema (P = 0.01). PA strain was also markedly correlated with right ventricular diastolic dysfunction measured by E/A ratios in the fully adjusted mix models (P = 0.02). Conclusion: PA strain is reduced in COPD, related in part to percent emphysema on CT scan, which may have implications for pulmonary small vessel flow and right ventricular function. Level of Evidence: 2 Technical Efficacy: Stage

Race and sex differences in response to endothelin receptor antagonists for pulmonary arterial hypertension

Background Recently studied therapies for pulmonary arterial hypertension (PAH) have improved outcomes among populations of patients, but little is known about which patients are most likely to respond to specific treatments. Differences in endothelin-1 biology between sexes and between whites and blacks may lead to differences in patients' responses to treatment with endothelin receptor antagonists (ERAs). Methods We conducted pooled analyses of deidentified, patient-level data from six randomized placebo-controlled trials of ERAs submitted to the US Food and Drug Administration to elucidate heterogeneity in treatment response. We estimated the interaction between treatment assignment (ERA vs placebo) and sex and between treatment and white or black race in terms of the change in 6-min walk distance from baseline to 12 weeks. Results Trials included 1,130 participants with a mean age of 49 years; 21% were men, 74% were white, and 6% were black. The placebo-adjusted response to ERAs was 29.7 m (95% CI, 3.7-55.7 m) greater in women than in men (P = .03). The placebo-adjusted response was 42.2 m for whites and −1.4 m for blacks, a difference of 43.6 m (95% CI, −3.5-90.7 m) (P = .07). Similar results were found in sensitivity analyses and in secondary analyses using the outcome of absolute distance walked. Conclusions Women with PAH obtain greater responses to ERAs than do men, and whites may experience a greater treatment benefit than do blacks. This heterogeneity in treatment-response may reflect pathophysiologic differences between sexes and races or distinct disease phenotypes

Impact of the COVID-19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR\u27s inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly-sponsored insurance during the COVID-19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly-sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID-19 pandemic. The relatively small impact of the COVID-19 pandemic on pulmonary hypertension-related outcomes was unexpected but may be due to pre-established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID-19 pandemic, patients who were on publicly-sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness

Right ventricular outflow tract velocity time integral-to-pulmonary artery systolic pressure ratio: a non-invasive metric of pulmonary arterial compliance differs across the spectrum of pulmonary hypertension.

Pulmonary arterial compliance (PAC), invasively assessed by the ratio of stroke volume to pulmonary arterial (PA) pulse pressure, is a sensitive marker of right ventricular (RV)-PA coupling that differs across the spectrum of pulmonary hypertension (PH) and is predictive of outcomes. We assessed whether the echocardiographically derived ratio of RV outflow tract velocity time integral to PA systolic pressure (RVOT-VTI/PASP) (a) correlates with invasive PAC, (b) discriminates heart failure with preserved ejection-associated PH (HFpEF-PH) from pulmonary arterial hypertension (PAH), and (c) is associated with functional capacity. We performed a retrospective cohort study of patients with PAH (n = 70) and HFpEF-PH (n = 86), which was further dichotomized by diastolic pressure gradient (DPG) into isolated post-capillary PH (DPG \u3c 7 mmHg; Ipc-PH, n = 54), and combined post- and pre-capillary PH (DPG ≥ 7 mm Hg; Cpc-PH, n = 32). Of the 156 patients, 146 had measurable RVOT-VTI or PASP and were included in further analysis. RVOT-VTI/PASP correlated with invasive PAC overall (ρ = 0.61, P \u3c 0.001) and for the PAH (ρ = 0.38, P = 0.002) and HFpEF-PH (ρ = 0.63, P \u3c 0.001) groups individually. RVOT-VTI/PASP differed significantly across the PH spectrum (PAH: 0.13 [0.010-0.25] vs. Cpc-PH: 0.20 [0.12-0.25] vs. Ipc-PH: 0.35 [0.22-0.44]; P \u3c 0.001), distinguished HFpEF-PH from PAH (AUC = 0.72, 95% CI = 0.63-0.81) and Cpc-PH from Ipc-PH (AUC = 0.78, 95% CI = 0.68-0.88), and remained independently predictive of 6-min walk distance after multivariate analysis (standardized β-coefficient = 27.7, 95% CI = 9.2-46.3; P = 0.004). Echocardiographic RVOT-VTI/PASP is a novel non-invasive metric of PAC that differs across the spectrum of PH. It distinguishes the degree of pre-capillary disease within HFpEF-PH and is predictive of functional capacity

Statement on imaging and pulmonary hypertension from the Pulmonary Vascular Research Institute (PVRI)

Pulmonary hypertension (PH) is highly heterogeneous and despite treatment advances it remains a life-shortening condition. There have been significant advances in imaging technologies, but despite evidence of their potential clinical utility, practice remains variable, dependent in part on imaging availability and expertise. This statement summarizes current and emerging imaging modalities and their potential role in the diagnosis and assessment of suspected PH. It also includes a review of commonly encountered clinical and radiological scenarios, and imaging and modeling-based biomarkers. An expert panel was formed including clinicians, radiologists, imaging scientists, and computational modelers. Section editors generated a series of summary statements based on a review of the literature and professional experience and, following consensus review, a diagnostic algorithm and 55 statements were agreed. The diagnostic algorithm and summary statements emphasize the key role and added value of imaging in the diagnosis and assessment of PH and highlight areas requiring further research

Health-related quality of life and survival in liver transplant candidates.

Health-related quality of life (HRQOL) is an important measure of the effects of chronic liver disease in affected patients that helps guide interventions to improve well-being. However, the relationship between HRQOL and survival in liver transplant candidates remains unclear. We examined whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Short Form 36 (SF-36) Health Survey were associated with survival in liver transplant candidates. We administered the SF-36 questionnaire (version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease study, a multicenter prospective cohort of patients evaluated for liver transplantation in 7 academic centers in the United States between 2003 and 2006. Cox proportional hazards models were used with death as the primary outcome and adjustment for liver transplantation as a time-varying covariate. The mean age of the 252 participants was 54 +/- 10 years, 64% were male, and 94% were white. During the 422 person years of follow-up, 147 patients (58%) were listed, 75 patients (30%) underwent transplantation, 49 patients (19%) died, and 3 patients were lost to follow-up. Lower baseline PCS scores were associated with an increased mortality rate despite adjustments for age, gender, Model for End-Stage Liver Disease score, and liver transplantation (P for the trend = 0.0001). The MCS score was not associated with mortality (P for the trend = 0.53). In conclusion, PCS significantly predicts survival in liver transplant candidates, and interventions directed toward improving the physical status may be helpful in improving outcomes in liver transplant candidates