Ambient Air Pollution Exposure and Sleep Quality in COPD.

Rationale: Ambient air pollution exposure is associated with respiratory morbidity among individuals with chronic obstructive pulmonary disease (COPD), particularly among those with concomitant obesity. Although people with COPD report high incidence of poor sleep quality, no studies have evaluated the association between air pollution exposure, obesity, and sleep disturbances in COPD. Methods: We analyzed data collected from current and former smokers with COPD enrolled in the Subpopulations and Intermediate Outcome Measures in COPD -Air Pollution ancillary study (SPIROMICS AIR). Socio-demographics and anthropometric measurements were collected, and 1-year mean historical ambient particulate matter (PM2.5) and ozone concentrations at participants' residences were estimated by cohort-specific spatiotemporal modeling. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and regression models were constructed to determine the association of 1-year PM2.5 (1Yr-PM2.5) and 1-year ozone (1Yr-ozone) with the PSQI score, and whether obesity modified the association. Results: In 1308 participants (age: 65.8±7.8 years, 42% women), results of regression analyses suggest that each 10µg/m3 increase in 1Yr-PM2.5 was associated with a 2.1-point increase in PSQI (P=0.03). Obesity modified the association between 1Yr-PM2.5 and PSQI (P=0.03). In obese and overweight participants, a 10µg/m3 increase in 1Yr-PM2.5 was associated with a higher PSQI (4.0 points, P<0.01, and 3.4 points, P<0.01, respectively); but no association in lean-normal weight participants (P=0.51). There was no association between 1 Yr-ozone and PSQI. Conclusions: Overweight and obese individuals with COPD appear to be susceptible to the effects of ambient PM2.5 on sleep quality. In COPD, weight and ambient PM2.5 may be modifiable risk factors to improve sleep quality.

Lung Function and the Risk of Exacerbation in the ß-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Trial.

Rationale: The BLOCK COPD (ß-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) study found that metoprolol was associated with a higher risk of severe exacerbation. Objectives: To determine the mechanism underlying these results, we compared changes in lung function over the course of the study between treatment groups and evaluated whether baseline bronchodilator response or early reduction in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) was associated with exacerbation risk. Methods: We compared changes in lung function (FEV1 and FVC) over the treatment period between treatment groups using linear mixed-effect models. Cox proportional hazards models were used to evaluate the association between baseline bronchodilator responsiveness (FEV1, FVC, and combined FEV1 and FVC), early post-randomization (14 d) change in lung function, and the interaction between treatment assignment and these measures with risk of any or severe or very severe exacerbations. Negative binomial models were used to evaluate the relationship between bronchodilator responsiveness, the interaction between bronchodilator responsiveness and treatment assignment, and exacerbation rate. Results: Over the 336-day treatment period, individuals in the metoprolol group had a significantly greater decrease in logarithmic FEV1 from baseline to visit on Day 28 than individuals in the placebo group. Individuals in the metoprolol group had a significantly greater decrease in FVC from baseline to visits on Days 14 and 28, and also a significantly greater decrease in logarithmic FVC from baseline to visits on Days 42 and 112 than individuals in the placebo group. There were no associations between early lung function reduction or interactions between lung function reduction and treatment assignment and time to any or severe or very severe exacerbations. There were no interactions between treatment arm and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. However, those with baseline FVC bronchodilator responsiveness had a higher rate of severe or very severe exacerbations (adjusted rate ratio, 1.62; 95% confidence interval, 1.04-2.48). Conclusions: Metoprolol was associated with reduced lung function during the early part of the treatment period, but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe or very severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT02587351).

Neighborhood Socioeconomic Deprivation in Young Adulthood and Future Respiratory Health: The CARDIA Lung Study.

PURPOSE: There are limited data on the relationship between neighborhood level factors and their association with lung health independent of individual socioeconomic status. We sought to determine whether baseline neighborhood level socioeconomic deprivation in young adults is associated with greater 20-year decline in lung function and higher risk of future lung disease, independent of baseline individual income, education, and smoking status. METHODS: This multicenter population-based cohort study included 2689 participants in Coronary Artery Risk Development in Young Adults (CARDIA) for whom neighborhood deprivation was determined at year 10 (baseline for study) and who had complete lung function measurements at years 10 and 30. Baseline neighborhood deprivation was defined using 1990 Census blocks as a combination of 4 factors involving median household income, poverty level, and educational achievement. The outcomes were decline in lung function over 20 years (year 10 to 30) and odds of emphysema (year 25). RESULTS: In multivariable regression models, greater baseline neighborhood deprivation was associated with greater decline in lung function (-2.34 mL/year excess annual decline in forced expiratory volume in 1 second (FEV1) in the highest versus lowest deprivation quartile (P = .014)). Furthermore, baseline neighborhood deprivation was independently associated with greater odds of emphysema (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.42-6.30). CONCLUSIONS: Residence in neighborhoods with greater socioeconomic deprivation in young adulthood, independent of individual income and smoking, is associated with greater 20-year decline in forced expiratory volume in 1 second and higher risk of future emphysema.

Racial Segregation and Respiratory Outcomes among Urban Black Residents with and at Risk of Chronic Obstructive Pulmonary Disease.

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (ß = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; ß = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; ß = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (ß = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (ß = -7.3; 95% CI, -10.9 to -3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (ß = 2.3; 95% CI, 0.7 to 3.9) and air trapping (ß = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.

Age-Dependent Associations Between 25-Hydroxy Vitamin D Levels and COPD Symptoms: Analysis of SPIROMICS.

INTRODUCTION: Age and vitamin D levels may affect symptom burden in chronic obstructive pulmonary disease (COPD). We used the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) to determine independent associations between vitamin D levels and COPD symptoms in different age strata. METHODS: Serum 25-hydroxy (OH)-vitamin D levels were modeled continuously and categorically (<20 ng/ml versus ≥20 ng/ml). Stratifying by age group (middle-age: 40-64 years old and older: >65 years old), multivariable modeling was performed to identify relationships between 25-OH-vitamin D levels and the COPD Assessment Test (CAT), the modified Medical Research Council score (mMRC), the St George's Respiratory Questionnaire (SGRQ) total and subdomain scores, the Veterans' Specific Activity Questionnaire, and the 6-minute walk test distance. RESULTS: InIn the middle-aged group, each 5 ng/ml higher 25-OH-vitamin D level was independently associated with more favorable CAT score (-0.35 [-0.67 to -0.03], P=0.03), total SGRQ (-0.91 [-1.65 to -0.17]; P=0.02), and the SGRQ subdomains (Symptoms:-1.07 [-1.96 to -0.18], P=0.02; Impact: -0.77 [-1.53 to -0.003], P=0.049; Activity: -1.07 [-1.96 to -0.18], P=0.02). These associations persisted after the addition of comorbidity score, reported vitamin D supplementation, outdoor time, or season of blood draw to models. No associations were observed between 25-OH-vitamin D levels and symptom scores in the older age group. DISCUSSION: When controlled for clinically relevant covariates, higher 25-OH-vitamin D levels are associated with more favorable respiratory-specific symptoms and quality-of-life assessments in middle-age but not older COPD individuals. Study of the role of vitamin D supplementation in the symptom burden of younger COPD patients is needed.

Defining Resilience to Smoking-related Lung Disease: A Modified Delphi Approach from SPIROMICS.

Rationale: Diagnosis of chronic obstructive pulmonary disease (COPD) relies on abnormal spirometry. However, spirometry may underestimate the effects of smoking, missing smokers with respiratory disease who have minimal or no airflow obstruction. Objectives: To develop a multidimensional definition of a lung-related "resilient smoker" that is useful in research studies and then identify a resilient smoker subgroup in the SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) cohort using this definition. Methods: We performed a three-round modified Delphi survey among a panel of COPD experts to identify and reach a consensus on clinical and radiographic domains to be included in a lung-related resilient smoker definition. Consensus on domains of resilience was defined as ⩾80% of experts voting "agree" or "strongly agree" on a 5-point Likert scale. The Delphi-derived definition of resilience was applied to SPIROMICS to identify resilient smokers, whom we then characterized using known biomarkers of COPD. Results: Consensus was achieved on 6 of 12 diagnostic items, which include cough and sputum production, dyspnea, radiographic measures of emphysema and small airways disease, exacerbations, and decline in forced expiratory volume in 1 second. Although 892 SPIROMICS participants were classified as smokers with preserved lung function by spirometry, only 149 participants (16.7%) qualified as resilient smokers by our definition. Blood biomarker expression of CRP (C-reactive protein) and sTNFRSF1A (soluble tumor necrosis receptor factor1A) was lower in resilient than nonresilient smokers (P = 0.02 and P = 0.03). Conclusions: A Delphi-derived consensus definition of resilient smoker identified 83.3% of smokers with preserved spirometry as "nonresilient" based on the presence of adverse effects of smoking on the lung. Resilient smokers were biologically distinct from nonresilient smokers based on CRP measurements. Clinical trial registered with ClinicalTrials.gov (NCT01969344).

Contribution of Individual and Neighborhood Factors to Racial Disparities in Respiratory Outcomes.

Rationale: Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD).Objectives: To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes.Methods: Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhood-level descriptors of SES both separately and sequentially.Measurements and Main Results: After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), and more air trapping on CT metrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12-35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness).Conclusions: Disadvantages by individual- and neighborhood-level SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities.

The Association Between Neighborhood Socioeconomic Disadvantage and Chronic Obstructive Pulmonary Disease.

Rationale: Individual socioeconomic status has been shown to influence the outcomes of patients with chronic obstructive pulmonary disease (COPD). However, contextual factors may also play a role. The objective of this study is to evaluate the association between neighborhood socioeconomic disadvantage measured by the area deprivation index (ADI) and COPD-related outcomes. Methods: Residential addresses of SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) subjects with COPD (FEV1/FVC <0.70) at baseline were geocoded and linked to their respective ADI national ranking score at the census block group level. The associations between the ADI and COPD-related outcomes were evaluated by examining the contrast between participants living in the most-disadvantaged (top quintile) to the least-disadvantaged (bottom quintile) neighborhood. Regression models included adjustment for individual-level demographics, socioeconomic variables (personal income, education), exposures (smoking status, packs per year, occupational exposures), clinical characteristics (FEV1% predicted, body mass index) and neighborhood rural status. Results: A total of 1800 participants were included in the analysis. Participants residing in the most-disadvantaged neighborhoods had 56% higher rate of COPD exacerbation (P<0.001), 98% higher rate of severe COPD exacerbation (P=0.001), a 1.6 point higher CAT score (P<0.001), 3.1 points higher SGRQ (P<0.001), and 24.6 meters less six-minute walk distance (P=0.008) compared with participants who resided in the least disadvantaged neighborhoods. Conclusion: Participants with COPD who reside in more-disadvantaged neighborhoods had worse COPD outcomes compared to those residing in less-disadvantaged neighborhoods. Neighborhood effects were independent of individual-level socioeconomic factors, suggesting that contextual factors could be used to inform intervention strategies targeting high-risk persons with COPD.

The Association of Low Income and High Stress with Acute Care Use in COPD Patients.

INTRODUCTION: Low-income chronic obstructive pulmonary disease (COPD) individuals are known to have higher rates of COPD-related hospitalizations and readmissions. Levels of psychological stress are also higher in low-income populations and may be associated with acute care use. We sought to: (1) determine the association between stress and acute care use in COPD, (2) evaluate the social determinants of health (SDH) in low and high stress individuals, and (3) determine the association between low income and high stress with acute care use. MATERIALS AND METHODS: Using results from a survey-based study of individuals with COPD at the University of Alabama (UAB), we used multivariable regression modeling to evaluate the association of high stress with acute care use (COPD-related emergency department [ED] visits or hospitalizations). We then compared SDH between low and high stress groups and evaluated the association of low income + high stress with acute care use in a secondary model. RESULTS: We included 126 individuals in our study. The high stress group was more likely to be < 65 years old and female. No differences in race, smoking, years of smoking, body mass index, dyspnea, or lung function (forced expiratory volume in 1 second [FEV1]%) by stress group were observed. The high stress group had a 2.5-fold increased adjusted odds of acute care use (adjusted odds ratio [AOR]95% confidence interval [CI], 2.51, 1.06-5.98) compared to the low stress group, while the low-income + high stress group had a 4-fold increased adjusted odds of acute care use (AOR, 95% CI, 4.38, 1.25-15-45) compared to high-income + low-stress group. CONCLUSIONS: Acute care use and stress are associated in COPD. These associations are more pronounced in the low-income + high stress population who disproportionately contribute to health care utilization and frequently lack the resources needed to cope with stress.

Factors influencing decline in quality of life in smokers without airflow obstruction: The COPDGene study.

INTRODUCTION: Current and former smokers with normal spirometry and with Preserved Ratio Impaired Spirometry (PRISm) experience respiratory events similar to chronic obstructive pulmonary disease (COPD) exacerbations. Exacerbations significantly reduce quality of life (QoL) in COPD patients however the effect of respiratory exacerbations on QoL in these groups is unknown. We hypothesized that exacerbations and change in exacerbation status would predict QoL decline among normal spirometry and PRISm participants in COPDGene. METHODS: COPDGene is a multicenter, longitudinal study in the U.S. designed to identify genetic determinants of COPD. We enrolled study subjects in Phase 1 of COPDGene and performed multivariable logistic regression models to determine independent predictors of decline in quality of life [>4 points on the St George's Respiratory Questionnaire (SGRQ)]. Separate analyses were performed for current and former smokers with normal spirometry and PRISm. Frequent exacerbator status was defined by > 2 moderate or >1 severe exacerbations in the year prior to the baseline and year 5 follow-up visits. RESULTS: Independent predictors of QoL deterioration included current smoking, higher exacerbation frequency, and a change from infrequent to frequent exacerbation status (REF: infrequent to infrequent exacerbation status) in both groups [PRISm (OR = 3.15,95%CI, 1.67-5.94), normal spirometry (OR = 4.72,95%CI, 3.25-6.86)]. A change from frequent to infrequent exacerbation status did not lower the odds of QoL decline in either cohort. CONCLUSION: Continued smoking and the onset of frequent exacerbations were predictors of QoL decline in smokers with normal spirometry and PRISm. Further studies are needed to identify modifiable factors associated with decline in QoL in smokers.

Application of the community health worker model in adult asthma and COPD in the U.S.: a systematic review.

BACKGROUND: With rising medical costs, stakeholders and healthcare professionals are exploring community-based solutions to relieve the burden of chronic diseases and reduce health care spending. The community health worker (CHW) model is one example that has proven effective in improving patient outcomes globally. We sought to systematically describe the effectiveness of community health worker interventions in improving patient reported outcomes and reducing healthcare utilization in the adult asthma and chronic obstructive pulmonary disease (COPD) populations in the U.S. METHODS: Studies were included if they were a randomized control trial or involved a pre-post intervention comparison with clearly stated disease specific outcomes, targeted adult patients with asthma or COPD, and were performed in the United States. Risk of bias was assessed using the Cochrane Risk of Bias tool. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria and was registered with PROSPERO. RESULT: The search yielded 4013 potential articles, of which 47 were chosen for full-text review and 4 were chosen for inclusion; all focused on asthma and three had a comparison group. CHW interventions demonstrated improvement in asthma-related quality of life, asthma control, home trigger scores, and asthma symptom free days. There were no studies that reported COPD specific outcomes as a result of CHW interventions. CONCLUSION: Emerging evidence suggests CHW interventions may improve some aspects of asthma related disease burden in adults, however additional studies with consistent outcome measures are needed to confirm their effectiveness. Further research is also warranted to evaluate the use of community health workers in the COPD population.

Determinants of cigarette smoking status in a national cohort of black and white adult ever smokers in the USA: a cross-sectional analysis of the REGARDS study.

OBJECTIVES: While awareness of cigarette smoking's harmful effects has increased, determinants associated with smoking status remain understudied, including potential racial differences. We aim to examine factors associated with former versus current smoking status and assess whether these associations differed by race. SETTING: We performed a cross-sectional analysis using the population-based Reasons for Geographic and Racial Differences in Stroke(REGARDS)study. OUTCOME MEASURES: Logistic regression was used to calculate the OR of former smoking status compared with current smoking status with risk factors of interest. Race interactions were tested using multiplicative interaction terms. RESULTS: 16 463 participants reported smoking at least 100 cigarettes in their lifetime. Seventy-three per cent (n=12 067) self-reported former-smoker status. Physical activity (reference (REF) <3×/week; >3×/week: OR=1.26, 95% CI 1.11 to 1.43), adherence to Mediterranean diet (REF: low; medium: OR=1.46, 95% CI 1.27 to 1.67; high: OR=2.20, 95% CI 1.84 to 2.64), daily television viewing time (REF: >4 hours; <1 hour: OR=1.32, 95% CI 1.10 to 1.60) and abstinence from alcohol use (REF: heavy; none: OR=1.50, 95% CI 1.18 to 1.91) were associated with former-smoker status. Male sex, higher education and income $35 000-$74 000 (REF: <$20 000) were also associated with former-smoker status. Factors associated with lower odds of reporting former-smoker status were younger age (REF: ≥65 years; 45-64 years: OR=0.34, 95% CI 0.29 to 0.39), black race (OR=0.62, 95% CI 0.53 to 0.72) and single marital status (REF: married status; OR=0.66, 95% CI 0.51 to 0.87), being divorced (OR=0.60, 95% CI 0.50 to 0.72) or widowed (OR=0.70, 95% CI 0.57 to 0.85). Significant interactions were observed between race and alcohol use and dyslipidaemia, such that black participants had higher odds of reporting former-smoker status if they were abstinent from alcohol (OR=2.32, 95% CI 1.47 to 3.68) or had a history of dyslipidaemia (OR=1.31, 95% CI 1.06 to 1.62), whereas these relationships were not statistically significant in white participants. CONCLUSION: Efforts to promote tobacco cessation should consist of targeted behavioural interventions that incorporate racial differences.

Results of a Medicare Bundled Payments for Care Improvement Initiative for Chronic Obstructive Pulmonary Disease Readmissions.

RATIONALE: Approximately 20% of Medicare beneficiaries hospitalized for acute exacerbations of chronic obstructive pulmonary disease (COPD) are readmitted within 30 days of discharge. In addition to implementing penalties for excess readmissions, the U.S. Centers for Medicare and Medicaid Services has developed Bundled Payments for Care Improvement (BPCI) initiatives to improve outcomes and control costs. OBJECTIVES: To evaluate whether a comprehensive COPD multidisciplinary intervention focusing on inpatient, transitional, and outpatient care as part of our institution's BPCI participation would reduce 30-day all-cause readmission rates for COPD exacerbations and reduce overall costs. METHODS: We performed a pre-postintervention study comparing all-cause readmissions and costs after index hospitalization for Medicare-only patients with acute exacerbation of COPD. The primary outcome was the difference in 30-day all-cause readmission rate compared with historical control subjects; secondary outcomes included the 90-day all-cause readmission rate and also health care costs compared with BPCI target prices. RESULTS: Seventy-eight consecutive Medicare patients were prospectively enrolled in the BPCI intervention in 2014 and compared with 109 patients in the historical group from 2012. Patients in BPCI were more likely to receive regular follow-up phone calls, pneumococcal and influenza vaccines, home health care, durable medical equipment, and pulmonary rehabilitation, and to attend pulmonary clinic. There was no difference in all-cause readmission rates at 30 days (BPCI, 12 events [15.4%] vs. non-BPCI, 19 events [17.4%]; P = 0.711), and 90 days (21 [26.9%] vs. 37 [33.9%]; P = 0.306). Compared with BPCI target prices, we incurred 4.3% lower 90-day costs before accounting for significant investment from the health system. CONCLUSIONS: A Medicare BPCI intervention did not reduce 30-day all-cause readmission rates or overall costs after hospitalization for acute exacerbation of COPD. Although additional studies enrolling larger numbers of patients at multiple centers may demonstrate the efficacy of our BPCI initiative for COPD readmissions, this is unlikely to be cost effective at any single center.

Implications of DRG Classification in a Bundled Payment Initiative for COPD.

OBJECTIVES: Institutions participating in the Medicare Bundled Payments for Care Improvement (BPCI) initiative invest significantly in efforts to reduce readmissions and costs for patients who are included in the program. Eligibility for the BPCI initiative is determined by diagnosis-related group (DRG) classification. The implications of this methodology for chronic diseases are not known. We hypothesized that patients included in a BPCI initiative for chronic obstructive pulmonary disease (COPD) would have less severe illness and decreased hospital utilization compared with those excluded from the bundled payment initiative. STUDY DESIGN: Retrospective observational study. METHODS: We sought to determine the clinical characteristics and outcomes of Medicare patients admitted to the University of Alabama at Birmingham Hospital with acute exacerbations of COPD between 2012 and 2014 who were included and excluded in a BPCI initiative. Patients were included in the analysis if they were discharged with a COPD DRG or with a non-COPD DRG but with an International Classification of Diseases, Ninth Revision code for COPD exacerbation. RESULTS: Six hundred and ninety-eight unique patients were discharged for an acute exacerbation of COPD; 239 (34.2%) were not classified into a COPD DRG and thus were excluded from the BPCI initiative. These patients were more likely to have intensive care unit (ICU) admissions (63.2% vs 4.4%, respectively; P <.001) and require noninvasive (46.9% vs 6.5%; P <.001) and invasive mechanical ventilation (41.4% vs 0.7%; P <.001) during their hospitalization than those in the initiative. They also had a longer ICU length of stay (5.2 vs 1.8 days; P = .011), longer hospital length of stay (10.3 days vs 3.9 days; P <.001), higher in-hospital mortality (14.6% vs 0.7%; P <.001), and greater hospitalization costs (median = $13,677 [interquartile range = $7489-$23,054] vs $4281 [$2718-$6537]; P <.001). CONCLUSIONS: The use of DRGs to identify patients with COPD for inclusion in the BPCI initiative led to the exclusion of more than one-third of patients with acute exacerbations who had more severe illness and worse outcomes and who may benefit most from the additional interventions provided by the initiative.

A case of peripheral T-cell lymphoma, not otherwise specified in a HCV and HTLV-II-positive patient, diagnosed by abdominal fluid cytology.

BACKGROUND: Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a rare neoplasm that typically presents as generalized lymphadenopathy. PTCL, NOS presenting as malignant ascites is rare. METHODS: A 61-year-old African-American man with past medical history of HCV, cryoglobulinemia, and cryptococcal pneumonia was admitted for dyspnea on exertion over a period of 1 month and new onset of abdominal distension. RESULTS: Ascites, splenomegaly, hepatomegaly and extensive lymphadenopathy were found by imaging. Paracentesis obtained 1.3 liter of abdominal fluid, the cytologic evaluation showed a monomorphic population of intermediate-sized lymphoid cells with irregular to convoluted nuclear contours. Fluid sent for flow cytometry showed an abnormal T-lymphocyte population expressing CD4, weak surface CD3 and absence of CD7. PCR studies of ascitic fluid detected a clonal T-lymphocyte population with T-cell receptor gamma gene rearrangement. Serologic testing for human T lymphotropic virus (HTLV) was positive for HTLV-II. Subsequent bone marrow biopsy revealed lymphomatous involvement. CD30 and ALK-1 immunostaining were negative. This case was classified as PTCL, NOS. CONCLUSIONS: PTCL, NOS can have unusual clinical presentation such as ascites and pleural effusion, and may also occur as a complication of immunodeficiency state. Further studies are needed to determine if HCV or HTLV-II viral infection is associated with PTCL.

Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas.

IMPORTANCE: Certain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia. OBJECTIVE: To determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients 66 years or older who were prescribed glipizide or glyburide and who also filled a prescription for 1 of the 16 antimicrobials most commonly prescribed for this population. METHODS: We assessed hypoglycemia events and associated Medicare costs in patients prescribed 1 of 7 antimicrobial agents thought to interact with sulfonylureas, using noninteracting antimicrobials as a comparison. We used a repeated measure logistic regression, controlling for age, sex, ethnicity, Medicaid eligibility, comorbidity, prior emergency department visits for hypoglycemia, prior hospitalizations for any cause, nursing home residence, and indication for the antimicrobial. We estimated odds of hypoglycemia, number needed to harm, deaths during hospitalization for hypoglycemia, and Medicare costs for hypoglycemia treatment. MAIN OUTCOMES AND MEASURES: Any hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure. RESULTS: In multivariable analyses controlling for patient characteristics and indication for antimicrobial drug use, clarithromycin (odds ratio [OR], 3.96 [95% CI, 2.42-6.49]), levofloxacin (OR, 2.60 [95% CI, 2.18-3.10]), sulfamethoxazole-trimethoprim (OR, 2.56 [95% CI, 2.12-3.10]), metronidazole (OR, 2.11 [95% CI, 1.28-3.47]), and ciprofloxacin (OR, 1.62 [95% CI, 1.33-1.97]) were associated with higher rates of hypoglycemia compared with a panel of noninteracting antimicrobials. The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. Patient factors associated with hypoglycemia included older age, female sex, black or Hispanic race/ethnicity, higher comorbidity, and prior hypoglycemic episode. In 2009, 28.3% of patients prescribed a sulfonylurea filled a prescription for 1 of these 5 antimicrobials, which were associated with 13.2% of all hypoglycemia events in patients taking sulfonylureas. The treatment of subsequent hypoglycemia adds $30.54 in additional Medicare costs to each prescription of 1 of those 5 antimicrobials given to patients taking sulfonylureas. CONCLUSIONS AND RELEVANCE: Prescription of interacting antimicrobial drugs to patients on sulfonylureas is very common, and is associated with substantial morbidity and increased costs.

Predictors of early readmission among patients 40 to 64 years of age hospitalized for chronic obstructive pulmonary disease.

RATIONALE: Various causes can contribute to the high rates of readmission among patients hospitalized with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine the frequency and predictors of early readmission among patients aged 40-64 years, hospitalized with COPD. METHODS: In a retrospective cohort study, using a large national commercial insurance database, we obtained the clinical information within 12 months of the index hospitalization and 30 days after discharge. MEASUREMENTS AND MAIN RESULTS: Primary outcome was early readmission, defined as hospitalization within 30 days of discharge. We categorized predictor variables as patient, provider, and system factors, and compared these variables between patients readmitted and those not readmitted. Logistic regression was used for multivariable analysis. Of 8,263 patients who met the inclusion criteria, 741 (8.9%) had early readmission. Multivariable analysis showed patient factors (male, history of heart failure, lung cancer, osteoporosis, and depression), provider factors (no prior prescription of statin within 12 mo of the index hospitalization and no prescription of short-acting bronchodilator, oral steroid and antibiotic on discharge), and system factors (length of stay, <2 or >5 d and lack of follow-up visit after discharge) were associated with early readmission among patients hospitalized with COPD. The C-statistic of the model including patient characteristics was 0.677 (95% confidence interval, 0.656-0.697), which was improved to 0.717 (95% confidence interval, 0.702-0.732) after addition of provider- and system-based factors. CONCLUSIONS: One of 11 patients hospitalized with COPD is readmitted within 30 days of discharge. Provider and system factors are important modifiable risk factors of early readmission.