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 < -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

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

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

Platelet activation in the postoperative period after lung transplantation

Objective During lung transplantation, cells in the pulmonary parenchyma are subjected to ischemia, hypothermic storage, and reperfusion injury. Platelets, whose granular contents include adhesion receptors, chemokines, and coactivating substances that activate inflammatory and coagulant cascades, likely play a critical role in the lung allograft response to ischemia and reperfusion. The platelet response to the pulmonary allograft, however, has never been studied. Here we report significant platelet activation immediately after lung transplantation. Methods We performed a prospective cohort study comparing markers of platelet activation in patients undergoing lung transplantation and patients undergoing nontransplant thoracotomy. Plasma levels of soluble P-selectin, soluble CD40 ligand, and platelet–leukocyte conjugates were measured before surgery, after skin closure, and at 6 postoperative hours. Results Both soluble P-selectin and soluble CD40 ligand levels increased significantly after lung transplantation but not after thoracotomy. Additionally, platelet–monocyte conjugate fluorescence was significantly higher after lung transplantation than after thoracotomy alone. Conclusion These findings suggest that platelet activation is significantly increased after lung transplantation beyond that expected from the postoperative state. The increase in circulating platelet–monocyte conjugates suggests an important interaction between platelets and inflammatory cells. Further research should examine whether platelet activation affects early graft function after lung transplantation

Plasma Intercellular Adhesion Molecule-1 and von Willebrand Factor in Primary Graft Dysfunction After Lung Transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75029/1/j.1600-6143.2007.01981.x.pd

Selective Serotonin Reuptake Inhibitor Use Is Associated with Right Ventricular Structure and Function: The MESA-Right Ventricle Study

PURPOSE:Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114). METHODS:SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex. RESULTS:After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48-5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19-1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02-12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes. CONCLUSIONS:SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study

Association of environmental tobacco smoke exposure in childhood with early emphysema in adulthood among nonsmokers: the MESA-lung study.

Mechanical stress to alveolar walls may cause progressive damage after an early-life insult such as exposure to environmental tobacco smoke (ETS). This hypothesis was examined by using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort aged 45-84 years, free of clinical cardiovascular disease, recruited from 6 US sites in 2000-2002. The MESA-Lung Study assessed a fractal, structural measure of early emphysema ("alpha," lower values indicate more emphysema) and a standard quantitative measure ("percent emphysema") from cardiac computed tomography scans. Childhood ETS exposure was assessed retrospectively as a report of living with one or more regular indoor smokers. Analyses included 1,781 nonsmokers (<100 cigarettes, 20 cigars, or 20 pipefulls in their lifetime and urinary cotinine levels <100 ng/mL); mean age was 61 years (standard deviation, 10), and 65% were women. Childhood ETS exposure from 2 or more smokers (17%) compared with none (52%) was associated with 0.05 lower alpha and 2.8 higher percent emphysema (P for trend = 0.04 and 0.01, respectively) after adjustment for demographic, anthropometric, parental, and participant characteristics, as well as adult exposures (e.g., cumulative residential air pollution exposure, exposure to ETS as an adult). Childhood ETS exposure was associated with detectable differences on computed tomography scans of adult lungs of nonsmokers. PMID: 19942575 [PubMed - indexed for MEDLINE]PMCID: PMC2800303 [Available on 2011/1/1]Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78014/1/Am._J._Epidemiol.-2010-Lovasi-54-62[1].pd

Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension

Background—Pulmonary arterial hypertension (PAH) is a progressive disease that causes exercise limitation, heart failure, and death. We aimed to determine the safety and efficacy of aspirin and simvastatin in PAH. Methods and Results—We performed a randomized, double-blind, placebo-controlled 2×2 factorial clinical trial of aspirin and simvastatin in patients with PAH receiving background therapy at 4 centers. A total of 92 patients with PAH were to be randomized to aspirin 81 mg or matching placebo and simvastatin 40 mg or matching placebo. The primary outcome was 6-minute walk distance at 6 months. Sixty-five subjects had been randomized when the trial was terminated by the Data Safety and Monitoring Board after an interim analysis showed futility in reaching the primary end point for simvastatin. After adjustment for baseline 6-minute walk distance, there was no significant difference in the 6-minute walk distance at 6 months between aspirin (n=32) and placebo (n=33; placebo-corrected difference −0.5 m, 95% confidence interval −28.4 to 27.4 m; P=0.97) or between simvastatin (n=32) and placebo (n=33; placebo-corrected difference −27.6 m, 95% confidence interval −59.6 to 4.3 m; P=0.09). There tended to be more major bleeding episodes with aspirin than with placebo (4 events versus 1 event, respectively; P=0.17). Conclusions—Neither aspirin nor simvastatin had a significant effect on the 6-minute walk distance, although patients randomized to simvastatin tended to have a lower 6-minute walk distance at 6 months. These results do not support the routine treatment of patients with PAH with these medications

Preoperative Plasma Club (Clara) Cell Secretory Protein Levels Are Associated With Primary Graft Dysfunction After Lung Transplantation

Inherent recipient factors, including pretransplant diagnosis, obesity and elevated pulmonary pressures, are established primary graft dysfunction (PGD) risks. We evaluated the relationship between preoperative lung injury biomarkers and PGD to gain further mechanistic insight in recipients. We performed a prospective cohort study of recipients in the Lung Transplant Outcomes Group enrolled between 2002 and 2010. Our primary outcome was Grade 3 PGD on Day 2 or 3. We measured preoperative plasma levels of five biomarkers (CC‐16, sRAGE, ICAM‐1, IL‐8 and Protein C) that were previously associated with PGD when measured at the postoperative time point. We used multivariable logistic regression to adjust for potential confounders. Of 714 subjects, 130 (18%) developed PGD. Median CC‐16 levels were elevated in subjects with PGD (10.1 vs. 6.0, p < 0.001). CC‐16 was associated with PGD in nonidiopathic pulmonary fibrosis (non‐IPF) subjects (OR for highest quartile of CC‐16: 2.87, 95% CI: 1.37, 6.00, p = 0.005) but not in subjects with IPF (OR 1.38, 95% CI: 0.43, 4.45, p = 0.59). After adjustment, preoperative CC‐16 levels remained associated with PGD (OR: 3.03, 95% CI: 1.26, 7.30, p = 0.013) in non‐IPF subjects. Our study suggests the importance of preexisting airway epithelial injury in PGD. Markers of airway epithelial injury may be helpful in pretransplant risk stratification in specific recipients. The authors demonstrate a relationship between perioperative CC‐16 blood levels and an increased risk of primary lung allograft dysfunction, particularly in those without idiopathic pulmonary fibrosis as a pretransplant diagnosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102697/1/ajt12541.pd