Persistence to Basal Insulin: Association With Health Outcomes in a Population With Type 2 Diabetes.

This study examined the association between persistence to basal insulin and clinical and economic health outcomes. The question of whether a persistence measure for basal insulin could be leveraged in quality measurement was also explored. Using the IBM-Truven MarketScan Commercial and Medicare Supplemental Databases from 1 January 2011 to 31 December 2015, a total of 14,126 subjects were included in the analyses, wherein 9,898 (70.1%) were categorized as persistent with basal insulin therapy. Basal insulin persistence was associated with lower A1C, fewer hospitalizations and emergency department visits, and lower health care expenditures. Quality measures based on prescription drug claims for basal insulin are feasible and should be considered for guiding quality improvement efforts.

Association between adherence with oral anticancer medications and short-term health care resource utilization: A 2010-2018 claims-based analysis.

BACKGROUND: There is limited evidence on the effect of adherence to oral anticancer medications on health care resource utilization (HRU) among patients with cancer. OBJECTIVE: To determine the association between adherence to oral anticancer medication and subsequent HRU. METHODS: A retrospective cohort study was conducted using Optum Clinformatics® Data Mart commercial claims database. Patients who initiated an oral anticancer medication between 2010 and 2017 were included. Proportion of days covered was used to calculate medication adherence in the first 6 months after oral anticancer medication initiation. All-cause HRU in the following 6 months was assessed. Multivariable negative binomial regressions were used to determine the association between oral anticancer medication adherence and HRU, after controlling for confounders. RESULTS: Of 37,938 patients, 51.9% were adherent to oral anticancer medications. Adherence with oral anticancer medication was significantly associated with more frequent physician office and outpatient visits for several cancer types with the strongest association among those with liver cancer (adjusted incidence rate ratio [aIRR] = 1.34; 95% CI = 1.18-1.52 and aIRR = 1.32; 95% CI = 1.13-1.55, respectively). Oral anticancer medication adherence was associated with more emergency department visits only among patients with lung cancer (aIRR = 1.22; 95% CI = 1.01-1.48). Oral anticancer medication adherence was significantly associated with a higher rate of inpatient hospitalizations and longer stays among patients with liver cancer (aIRRs were 1.45 [95% CI = 1.02-2.05] and 2.15 [95% CI = 1.21-3.81], respectively), whereas hospitalizations were fewer and length of stay was shorter among patients with colorectal cancer who were adherent with oral anticancer medication (aIRRs were 0.77 [95% CI = 0.68-0.86] and 0.77 [95% CI = -0.66 to 0.90], respectively). Other measures did not reveal statistically significant differences in HRU among adherent and nonadherent patients for the cancer types included in the study. CONCLUSIONS: HRU following the initial phase of oral anticancer medication therapy was generally similar among adherent and nonadherent patients. We observed a slightly higher rate of office and outpatient visits among adherent patients, which may reflect ongoing monitoring among patients continuing oral anticancer medication. Further studies are needed to determine how oral anticancer medication adherence may affect HRU over a longer time period.

Associations between pharmacy choice and influenza vaccination: Mail order vs community pharmacy users.

BACKGROUND: Despite the effectiveness of vaccines, US adult vaccination rates remain low. This is especially true for the influenza vaccine, which is recommended annually and widely available. The accessibility of community pharmacies as convenient places to receive influenza vaccines has been shown to increase uptake. However, use of mail order pharmacies may reduce in-person pharmacist encounters and reduce the likelihood that users receive annual influenza vaccines. OBJECTIVE: To determine the association between the type of pharmacy a patient uses and their likelihood of receiving an influenza vaccine. METHODS: This cross-sectional cohort study used the 2018 Medical Expenditure Panel Survey to observe noninstitutionalized US adult pharmacy users. Pharmacy type was dichotomized into community use only vs any mail order pharmacy use. Multivariable weighted logistic regression was used to identify associations between the type of pharmacy used and influenza vaccination, adjusting for sociodemographic, health status, and health care access and utilization confounders. All analyses were stratified by age (< 65 and ≥ 65 years). RESULTS: The aged younger than 65 years and aged 65 years and older samples had 8,074 and 4,037 respondents who represented 95,930,349 and 40,163,276 weighted observations, respectively. Compared with community pharmacy users, mail order users were more likely to be aged 65 and older, be White, have high income, and have a usual source of care (P < 0.0001). Adjusted odds ratios (AORs) for influenza vaccination were significantly lower among community pharmacy users than mail order users among individuals aged younger than 65 years (AOR=0.71; 95% CI = 0.580.87) but was not significant among those aged 65 years and older (AOR = 0.87; 95% CI = 0.69-1.09). CONCLUSIONS: Community pharmacy users aged younger than 65 years are less likely to receive the influenza vaccine than their mail order pharmacy user counterparts. These counterintuitive results could be caused by residual confounding due to differences in factors that influence pharmacy use type and vaccination likelihood. Further exploration is needed to account for differences between these populations that independently drive vaccination choice. DISCLOSURES: Dr Burbage was a fellow in the Real World Evidence, Population Health and Quality Research Postdoctoral Fellowship Program in collaboration with University of North Carolina Eshelman School of Pharmacy and Pharmacy Quality Alliance, and supported by Janssen Scientific Affairs at the time of this study. She is now employed by Janssen Scientific Affairs. Dr Parikh is an employee of Pharmacy Quality Alliance. Dr Campbell was employed by Pharmacy Quality Alliance at the time of the study. He is now employed by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Dr Ramachandran has received an unrelated research contract with Pharmacy Quality Alliance. Dr Gatwood has received vaccine-related research grants from Merck & Co. and GlaxoSmithKline unrelated to this project and consulting fees for a vaccine-related expert panel with Merck & Co. unrelated to this manuscript and is an advisory board member with Janssen Scientific Affairs. Dr. Urick was employed by the UNC Eshelman School of Pharmacy at the time of this writing and is currently employed by Prime Therapeutics. He has received community pharmacy-related consulting fees from Cardinal Health and Pharmacy Quality Solutions unrelated to this work. Dr Ozawa has a research grant from Merck & Co. unrelated to this project. This project did not receive funding from any agency in the public, commercial, or not-for-profit sectors.

Predictors of adherence to oral anticancer medications: An analysis of 2010-2018 US nationwide claims.

BACKGROUND: Various factors, including patient demographic and socioeconomic characteristics, patient out-of-pocket (OOP) costs, therapy-related factors, clinical characteristics, and health-system factors, can affect patient adherence to oral anticancer medications (OAMs). OBJECTIVE: To determine the proportion of patients initiating oral anticancer therapy who were adherent to OAMs and to identify significant predictors of adherence to OAMs, including patient OOP costs and patient demographics. METHODS: A retrospective cohort study was conducted using data from Optum Clinformatics Data Mart commercial claims database for 2010-2018. Patients with a new pharmacy claim for an OAM between July 1, 2010, and December 31, 2017, were followed for 6 months to ascertain their medication adherence, which was defined as a proportion of days covered value of at least 0.8. Average monthly patient OOP costs for OAM prescriptions were categorized as lower OOP costs (quartiles 1-3) and higher OOP costs (quartile 4). Separate multivariable logistic regressions were conducted to identify predictors of OAM nonadherence for each cancer type. RESULTS: Out of 37,938 patients with cancer, 51.9% were adherent to OAMs, with adherence ranging from 32.8% among those with liver cancer to 70.4% among those with brain tumor. The average monthly OOP costs of OAMs also differed by cancer type, ranging from $749 (SD = $1,014) among patients with blood cancer to $106 (SD = $439) among those with prostate cancer. Higher patient OOP costs were associated with higher odds of OAM nonadherence for many cancer types, including renal cancer (adjusted odds ratio [AOR] = 3.91; 95% CI = 2.80-5.47) and breast cancer (AOR = 1.26; 95% CI = 1.13-1.41). Additionally, patients with inpatient hospitalizations during the 6 months following OAM initiation had significantly higher odds of OAM nonadherence for all cancer types except for stomach cancer. Among patients with stomach cancer, male sex was associated with lower odds of OAM nonadherence (AOR = 0.60; 95% CI = 0.37-0.97). Among patients with renal or stomach cancer, those who had Medicare low-income subsidy had higher odds of OAM nonadherence compared with those with commercial insurance coverage. Among patients with blood cancers, Black and Hispanic patients had higher odds of OAM nonadherence compared with White patients (AOR = 1.48; 95% CI = 1.25-1.75 and AOR = 1.38; 95% CI = 1.13-1.68, respectively). CONCLUSIONS: Overall adherence to OAMs was suboptimal, and for several cancer types, adherence was worse among patients with higher OOP costs, those who were hospitalized, and those who received Medicare low-income subsidy. Policies addressing cost and access to OAMs and health-system strategies to address barriers to the effective use of OAMs are needed to improve patient access to these vital medications. DISCLOSURES: This study was funded by joint funding from the Pharmacy Quality Alliance and the National Pharmaceutical Council (NPC). Drs Vyas and Kogut were partially supported by this joint funding. Mr Descoteaux was supported by this joint funding for performing data analysis. The content is solely the responsibility of the authors and does not necessarily represent the official views of PQA or NPC. Dr Campbell completed this work during his employment at Pharmacy Quality Alliance; he is now an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ.

Factors Associated With Postprocedure Opioid Prescribing and Persistent Opioid Use Among Opioid-naive Patients: A Nationally Representative Sample.

OBJECTIVE: Examine factors associated with postprocedure opioid receipt and persistent opioid use among opioid-naive patients in a nationally representative sample. SUMMARY BACKGROUND DATA: We used panels 18-20 in the Medical Expenditures Panel Survey (MEPS) between the years 2013 and 2015. Respondents ages 18 and over with any self-reported procedure in the previous year with complete data on the outcome variables for the remainder of the 2-year study period. METHODS: This prospective observational study used multivariable regression to determine factors associated with postprocedure opioid receipt and persistent opioid use among opioid-naive patients, adjusting for sociodemographic, health, and procedure-related characteristics. RESULTS: Adjusted models showed younger age, Western location (AOR = 1.38; 95% CI = 1.02, 1.86), and high-school degree (AOR = 1.60; CI = 1.14, 2.26) were associated with higher odds of postprocedure opioid receipt. Patients who had procedures in an inpatient (AOR: 5.71; CI: 4.31-7.56), outpatient (AOR = 3.77; CI = 2.87,4.95), and dental setting (AOR = 2.86; CI = 1.45, 5.63), and musculoskeletal diagnoses (AOR = 2.23; CI = 1.39, 3.58) and injuries (AOR = 2.04; CI = 1.29, 3.23) were more likely to have postprocedure opioid receipt. Persistent opioid use was associated with Midwest (AOR = 2.06; CI = 1.08, 3.95) and Northeast location (AOR = 2.45; CI = 1.03, 3.95), musculoskeletal diagnosis (AOR = 3.91; CI = 1.23, 8.31), public insurance (AOR = 2.07; CI = 1.23-3.49), and positive depression screener (AOR = 3.36; CI = 2.04, 5.55). CONCLUSIONS: Procedures account for a large portion of opioid prescriptions among opioid-naive patients. This study provides evidence to inform national guidelines for opioid prescribing and postprocedure pain management.

Health Care Disparities in Race-Ethnic Minority Communities and Populations: Does the Availability of Health Care Providers Play a Role?

OBJECTIVES: To examine disparities in use and access to different health care providers by community and individual race-ethnicity and to test provider supply as a potential mediator. DATA SOURCES: National secondary data from 2014 Medical Expenditure Panel Survey, 5-year estimates (2010-2014) from American Community Survey, and 2014 InfoUSA. STUDY DESIGN: Multiple logistic regression models examined the association of community and individual race-ethnicity with reported health care visits and access. Mediation analyses tested the role of provider supply. DATA EXTRACTION METHODS: Individual-level survey data were linked to race-ethnic composition and health business counts of the respondent's primary care service area (PCSA). PRINCIPAL FINDINGS: Minority PCSAs are significantly and independently associated with lower odds of having a visit to a physician assistant/nurse practitioner, dentist, or other health professionals and having a usual care provider (all p < 0.05). Few significant associations were observed for integrated PCSAs or for health provider supply. A modest mediation effect for provider supply was observed for travel time to usual care provider and visit to other health professionals. CONCLUSIONS: Use of a range of health services is lower in minority communities and individuals. However, provider supply was not an important explanatory factor of these disparities.

VALUE AND PERFORMANCE OF ACCOUNTABLE CARE ORGANIZATIONS: A COST-MINIMIZATION ANALYSIS.

OBJECTIVES: Determine the relationship between quality of an accountable care organization (ACO) and its long-term reduction in healthcare costs. METHODS: We conducted a cost minimization analysis. Using Centers for Medicare and Medicaid cost and quality data, we calculated weighted composite quality scores for each ACO and organization-level cost savings. We used Markov modeling to compute the probability that an ACO transitioned between different quality levels in successive years. Considering a health-systems perspective with costs discounted at 3 percent, we conducted 10,000 Monte Carlo simulations to project long-term cost savings by quality level over a 10-year period. We compared the change in per-member expenditures of Pioneer (early-adopters) ACOs versus Medicare Shared Savings Program (MSSP) ACOs to assess the impact of coordination of care, the main mechanism for cost savings. RESULTS: Overall, Pioneer ACOs saved USD 641.24 per beneficiary and MSSP ACOs saved USD 535.59 per beneficiary. By quality level: (a) high quality organizations saved the most money (Pioneer: USD 459; MSSP: USD 816); (b) medium quality saved some money (Pioneer: USD 222; MSSP: USD 105); and (c) low quality suffered financial losses (Pioneer: USD -40; MSSP: USD -386). CONCLUSIONS: Within the existing fee-for-service healthcare model, ACOs are a mechanism for decreasing costs by improving quality of care. Higher quality organizations incorporate greater levels of coordination of care, which is associated with greater cost savings. Pioneer ACOs have the highest level of integration of services; hence, they save the most money.

Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema.

Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50-79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema.

Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study.

RATIONALE: Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-ß and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-ß, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking. OBJECTIVES: To determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT. METHODS: The Multi-Ethnic Study of Atherosclerosis researchers recruited participants ages 45-84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than -950 Hounsfield units on CTs. Mixed-effects regression models were used to adjust for confounders. RESULTS: Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P < 0.001). Indications for ACE inhibitor or ARB drugs (hypertension and diabetes) and other medications for hypertension and diabetes were not associated independently with change in percent emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function. CONCLUSIONS: In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers. Randomized clinical trials of ACE and ARB agents are warranted for the prevention and treatment of emphysema.

Does the quality of safetalk motivational interviewing counseling predict sexual behavior outcomes among people living with HIV?

OBJECTIVE: Although past research has demonstrated a link between the quality of motivational interviewing (MI) counseling and client behavior change, this relationship has not been examined in the context of sexual risk behavior among people living with HIV/AIDS. We studied MI quality and unprotected anal/vaginal intercourse (UAVI) in the context of SafeTalk, an evidence-based secondary HIV prevention intervention. METHODS: We used a structured instrument (the MISC 2.0 coding system) as well as a client-reported instrument to rate intervention sessions on aspects of MI quality. Then we correlated client-reported UAVI with specific counseling behaviors and the proportion of interactions that achieved MI quality benchmarks. RESULTS/CONCLUSION: Higher MISC-2.0 global ratings and a higher ratio of reflections to questions both significantly predicted fewer UAVI acts at 8-month follow-up. Analysis of client ratings, which was more exploratory, showed that clients who rated their sessions higher in counselor acceptance, client disclosure, and relevance reported higher numbers of UAVIs, whereas clients who selected higher ratings for perceived benefit were more likely to have fewer UAVI episodes. PRACTICE IMPLICATIONS: Further research is needed to determine the best methods of translating information about MI quality into dissemination of effective MI interventions with people living with HIV.

Assessing electronic health record implementation challenges using item response theory.

OBJECTIVES: To assess the importance of commonly identified issues in electronic health record (EHR) implementation using item response theory (IRT). STUDY DESIGN: Secondary data from the 2012 American Hospital Association's Annual Survey Information Technology Supplement were used in the analyses. Results were compared and contrasted with the standard descriptive statistic frequencies that have been used to guide most recommendations made using the same data. METHODS: IRT was used to measure the magnitude of difficulty that particular challenges pose in implementing EHRs that meet federal guidelines for Meaningful Use. RESULTS: The IRT analyses yielded significantly different results from descriptive statistics in estimating the magnitude of specific EHR implementation challenges. In particular, IRT revealed that "obtaining physician cooperation" and "ongoing costs of maintaining and upgrading systems" were the most challenging implementation features. However, the frequency counts identified "upfront capital costs" and "complexity of meeting Meaningful Use criteria within implementation timeline" as the most challenging implementation features. CONCLUSIONS: For managers and policy makers, having an accurate assessment of EHR implementation challenges is essential to designing effective programs. IRT provides a statistical approach that allows prior studies to be assessed more accurately and future studies to retain the easier-to-use, check-all-that-apply survey structure while gaining valuable information.

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

RATIONALE: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. OBJECTIVES: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. METHODS: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. MEASUREMENTS AND MAIN RESULTS: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. CONCLUSIONS: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

Cor pulmonale parvus in chronic obstructive pulmonary disease and emphysema: the MESA COPD study.

BACKGROUND: The classic cardiovascular complication of chronic obstructive pulmonary disease (COPD) is cor pulmonale or right ventricular (RV) enlargement. Most studies of cor pulmonale were conducted decades ago. OBJECTIVES: This study sought to examine RV changes in contemporary COPD and emphysema using cardiac magnetic resonance (CMR) imaging. METHODS: We performed a case-control study nested predominantly in 2 general population studies of 310 participants with COPD and control subjects 50 to 79 years of age with ≥10 pack-years of smoking who were free of clinical cardiovascular disease. RV volumes and mass were assessed using magnetic resonance imaging. COPD and COPD severity were defined according to standard spirometric criteria. The percentage of emphysema was defined as the percentage of lung regions <-950 Hounsfield units on full-lung computed tomography; emphysema subtypes were scored by radiologists. Results were adjusted for age, race/ethnicity, sex, height, weight, smoking status, pack-years, systemic hypertension, and sleep apnea. RESULTS: Right ventricular end-diastolic volume (RVEDV) was reduced in COPD compared with control subjects (-7.8 ml; 95% confidence interval: -15.0 to -0.5 ml; p = 0.04). Increasing severity of COPD was associated with lower RVEDV (p = 0.004) and lower RV stroke volume (p < 0.001). RV mass and ejection fraction were similar between the groups. A greater percentage of emphysema also was associated with lower RVEDV (p = 0.005) and stroke volume (p < 0.001), as was the presence of centrilobular and paraseptal emphysema. CONCLUSIONS: RV volumes are lower without significant alterations in RV mass and ejection fraction in contemporary COPD, and this reduction is related to the greater percentage of emphysema on computed tomography.

Impaired left ventricular filling in COPD and emphysema: is it the heart or the lungs? The Multi-Ethnic Study of Atherosclerosis COPD Study.

BACKGROUND: COPD and heart failure with preserved ejection fraction overlap clinically, and impaired left ventricular (LV) filling is commonly reported in COPD. The mechanism underlying these observations is uncertain, but may include upstream pulmonary dysfunction causing low LV preload or intrinsic LV dysfunction causing high LV preload. The objective of this study is to determine if COPD and emphysema are associated with reduced pulmonary vein dimensions suggestive of low LV preload. METHODS: The population-based Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers aged 50 to 79 years who were free of clinical cardiovascular disease. COPD was defined by spirometry. Percent emphysema was defined as regions < -910 Hounsfield units on full-lung CT scan. Ostial pulmonary vein cross-sectional area was measured by contrast-enhanced cardiac magnetic resonance and expressed as the sum of all pulmonary vein areas. Linear regression was used to adjust for age, sex, race/ethnicity, body size, and smoking. RESULTS: Among 165 participants, the mean (± SD) total pulmonary vein area was 558 ± 159 mm2 in patients with COPD and 623 ± 145 mm2 in control subjects. Total pulmonary vein area was smaller in patients with COPD (-57 mm2; 95% CI, -106 to -7 mm2; P = .03) and inversely associated with percent emphysema (P < .001) in fully adjusted models. Significant decrements in total pulmonary vein area were observed among participants with COPD alone, COPD with emphysema on CT scan, and emphysema without spirometrically defined COPD. CONCLUSIONS: Pulmonary vein dimensions were reduced in COPD and emphysema. These findings support a mechanism of upstream pulmonary causes of underfilling of the LV in COPD and in patients with emphysema on CT scan.

Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease study.

RATIONALE: Basic research implicates alveolar endothelial cell apoptosis in the pathogenesis of chronic obstructive pulmonary disease (COPD) and emphysema. However, information on endothelial microparticles (EMPs) in mild COPD and emphysema is lacking. OBJECTIVES: We hypothesized that levels of CD31(+) EMPs phenotypic for endothelial cell apoptosis would be elevated in COPD and associated with percent emphysema on computed tomography (CT). Associations with pulmonary microvascular blood flow (PMBF), diffusing capacity, and hyperinflation were also examined. METHODS: The Multi-Ethnic Study of Atherosclerosis COPD Study recruited participants with COPD and control subjects age 50-79 years with greater than or equal to 10 pack-years without clinical cardiovascular disease. CD31(+) EMPs were measured using flow cytometry in 180 participants who also underwent CTs and spirometry. CD62E(+) EMPs phenotypic for endothelial cell activation were also measured. COPD was defined by standard criteria. Percent emphysema was defined as regions less than -950 Hounsfield units on full-lung scans. PMBF was assessed on gadolinium-enhanced magnetic resonance imaging. Hyperinflation was defined as residual volume/total lung capacity. Linear regression was used to adjust for potential confounding factors. MEASUREMENTS AND MAIN RESULTS: CD31(+) EMPs were elevated in COPD compared with control subjects (P = 0.03) and were notably increased in mild COPD (P = 0.03). CD31(+) EMPs were positively related to percent emphysema (P = 0.045) and were inversely associated with PMBF (P = 0.047) and diffusing capacity (P = 0.01). In contrast, CD62E(+) EMPs were elevated in severe COPD (P = 0.003) and hyperinflation (P = 0.001). CONCLUSIONS: CD31(+) EMPs, suggestive of endothelial cell apoptosis, were elevated in mild COPD and emphysema. In contrast, CD62E(+) EMPs indicative of endothelial activation were elevated in severe COPD and hyperinflation.

Quantitative and semiquantitative measures of regional pulmonary microvascular perfusion by magnetic resonance imaging and their relationships to global lung perfusion and lung diffusing capacity: the multiethnic study of atherosclerosis chronic obstructive pulmonary disease study.

OBJECTIVES: The aim of this study was to evaluate the quantitative and semiquantitative measures of regional pulmonary parenchymal perfusion in patients with chronic obstructive pulmonary disease (COPD) in relationship to global lung perfusion (GLP) and lung diffusing capacity (DLCO). MATERIALS AND METHODS: A total of 143 participants in the Multiethnic Study of Atherosclerosis COPD Study were examined by dynamic contrast-enhanced pulmonary perfusion magnetic resonance imaging (MRI) at 1.5 T. Pulmonary microvascular blood flow (PBF) was calculated on a pixel-by-pixel basis by using a dual-bolus technique and the Fermi function model. Semiquantitative parameters for regional pulmonary microvascular perfusion were calculated from signal intensity-time curves in the lung parenchyma. Intraoberserver and interobserver coefficients of variation (CVs) and correlations between quantitative and semiquantitative MRI parameters and with GLP and DLCO were determined. RESULTS: Quantitative and semiquantitative parameters of pulmonary microvascular perfusion were reproducible, with CVs for all parameters of less than 10%. Furthermore, these MRI parameters were correlated with GLP and DLCO, and there was good agreement between PBF and GLP. Quantitative and semiquantitative MRI parameters were closely correlated (eg, r = 0.86 for maximum signal increase with PBF). In participants without COPD, the physiological distribution of pulmonary perfusion could be determined by regional MRI measurements. CONCLUSION: Regional pulmonary microvascular perfusion can reliably be quantified from dynamic contrast-enhanced MRI. Magnetic resonance imaging-derived quantitative and semiquantitative perfusion measures correlate with GLP and DLCO.