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Rationale: Diagnosis of chronic obstructive pulmonary disease (COPD) relies on abnormal spirometry. However, spirometry may underestimate the effects of smoking, missing smokers with respiratory di...

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 (PM(2.5)) 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 PM(2.5 )(1Yr-PM(2.5)) 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/m(3) increase in 1Yr-PM(2.5 )was associated with a 2.1-point increase in PSQI (P=0.03). Obesity modified the association between 1Yr-PM(2.5) and PSQI (P=0.03). In obese and overweight participants, a 10µg/m(3) increase in 1Yr-PM(2.5) was associated with a higher PSQI (4.0 points, P

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.Objective...

Author(s): Galiatsatos, Panagis; Woo, Han; Paulin, Laura M; Kind, Amy; Putcha, Nirupama; Gassett, Amanda J; Cooper, Christopher B; Dransfield, Mark T; Parekh, Trisha M; Oates, Gabriela R; Barr, R Graham; Comellas, Alejandro P; Han, Meilan K; Peters, Stephen P; Krishnan, Jerry A; Labaki, Wassim W; McCormack, Meredith C; Kaufman, Joel D; Hansel, Nadia N | Abstract: RationaleIndividual 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.MethodsResidential addresses of SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) subjects with COPD (FEV1/FVC l0.70) 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.ResultsA total of 1800 participants were included in the analysis. Participants residing in the most-disadvantaged neighborhoods had 56% higher rate of COPD exacerbation (Pl0.001), 98% higher rate of severe COPD exacerbation (P=0.001), a 1.6 point higher CAT score (Pl0.001), 3.1 points higher SGRQ (Pl0.001), and 24.6 meters less six-minute walk distance (P=0.008) compared with participants who resided in the least disadvantaged neighborhoods.ConclusionParticipants 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.

Purpose Adherence to pulmonary rehabilitation (PR) is low. This qualitative study used the PRECEDE model to identify predisposing (intrapersonal), reinforcing (interpersonal), and enabling (structural) factors acting as barriers or facilitators of adherence to PR, and elicit recommendations for solutions from patients with chronic obstructive pulmonary disease (COPD). Methods Focus groups with COPD patients who had attended PR in the past year were conducted. Sessions were recorded, transcribed verbatim, and coded independently by 2 coders, who then jointly decided on the final coding scheme. Data were summarized across groups, and analysis was used a thematic approach with constant comparative method to generate categories. Results Five focus groups with 24 participants each were conducted. Participants (mean age 62 yr) were 54% male, and 67% black. More than half had annual income less than $20 000, 17% were current smokers, and 54% had low adherence (less than 35% of prescribed PR sessions). The most prominent barriers included physical ailments and lack of motivation (intrapersonal), no support system (interpersonal), transportation difficulties, and financial burden (structural). The most prominent facilitators included health improvement, personal determination (intrapersonal), support from peers, family, and friends (interpersonal), and program features such as friendly staff and educational component of sessions (structural). Proposed solutions included incentives to maintain motivation, tobacco cessation support (intrapersonal), educating the entire family (interpersonal), transportation assistance, flexible program scheduling, and financial assistance (structural). Conclusion Health limitations, social support, transportation and financial difficulties, and program features impact ability of patients to attend PR. Interventions addressing these interpersonal, intrapersonal, and structural barriers are needed to facilitate adherence to PR.

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 (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: In 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.

Background Millions of Americans are living in food deserts in the United States, however the role of the local food environment on COPD has not been studied. The aim of this study is to determine the association between food deserts and COPD-related outcomes. Method In this cross-sectional analysis we linked data collected from SPIROMICS (SubPopulations and InteRmediate Outcome Measures in COPD Study) between 2010 and 2015 and food desert data, defined as an underserved area that lacks access to affordable healthy foods, from the Food Access Research Atlas. COPD outcomes include percentage of predicted forced expiratory volume in one second (FEV1%), St. George’s Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), 6-min walk distance test (6MWD), exacerbations, and air trapping. We used generalized linear mixed models to evaluate the association between living in food deserts and respiratory outcomes, adjusting for age, gender, race, education, income, marital status, BMI, smoking status, pack years, and urban status Results Among 2713 participants, 22% lived in food deserts. Participants living in food deserts were less likely to be white and more likely to have a lower income than those who did not live in food deserts. In the adjusted model controlling for demographics and individual income, living in food deserts was associated lower FEV1% (β = – 2.51, P = 0.046), higher air trapping (β = 2.47, P = 0.008), worse SGRQ (β = 3.48, P = 0.001) and CAT (β = 1.20, P = 0.003) scores, and 56% greater odds of severe exacerbations (P = 0.004). Results were consistent when looking at food access alone, regardless of whether participants lived in low income areas. Conclusions Findings suggest an independent association between food desert and food access alone with COPD outcomes. Health program planning may benefit from addressing disparities in access to food.

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.

BackgroundThe purpose of this study was to explore the association between perceived social support and COPD outcomes and to determine whether the associations are mediated by depressive symptoms.MethodsSubjects with COPD who were enrolled as part of SPIROMICS were included in this analysis. Questionnaires relating to quality of life, symptom burden, and functional status were administered at annual clinic visits for over a 3 year period. In both cross-sectional and longitudinal analyses, we examined the association of social support as measured by the FACIT-F with COPD outcomes. Cross sectional analyses used multivariable linear or logistic regression, adjusting for covariates. For longitudinal analyses, generalized linear mixed models with random intercepts were used. Models were adjusted with and without depressive symptoms and mediation analyses performed.ResultsOf the 1831 subjects with COPD, 1779 completed the FACIT- F questionnaire. In adjusted cross-sectional analysis without depressive symptoms, higher perceived social support was associated with better quality of life, well-being, 6 minute walk distance, and less dyspnea. When also adjusting for depressive symptoms, all associations between social support and COPD outcomes were attenuated and no longer statistically significant. Mediation analysis suggested that depressive symptoms explained the majority (> = 85%) of the association between social support and measured COPD outcomes. Results of the longitudinal analysis were consistent with the cross-sectional analyses. There was no association between social support and odds of exacerbations.ConclusionHigher social support was associated with better COPD outcomes across several measures of morbidity including quality of life, respiratory symptoms, and functional status. In addition, these associations were largely attenuated when accounting for depressive symptoms suggesting that the beneficial association of social support with COPD outcomes may be largely mediated by the association between social support and depression.Trial registrationSPIROMICS was approved by Institutional Review Boards at each center and all participants provided written informed consent (clinicaltrials.gov:NCT01969344).

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 [FEV(1)]%) 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.

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.

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.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.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.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.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.

Multiple factors contribute to the complex link between cardiovascular disease (CVD) and chronic lung diseases (CLD). Despite having numerous shared risk factors including smoking and socioeconomic status, there is now growing evidence to suggest potential causality between CLD and CVD rather than simple association. In this chapter, we will review the pathobiologic processes that may drive the development of CVD in patients with CLD.

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

ObjectivesWhile 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.SettingWe performed a cross-sectional analysis using the population-based Reasons for Geographic and Racial Differences in Stroke(REGARDS)study.Outcome measuresLogistic 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.Results16 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: 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; ConclusionEfforts to promote tobacco cessation should consist of targeted behavioural interventions that incorporate racial differences.

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods: Four key disease characteristics – environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry – were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15–6.48) in those with all 4 disease characteristics. Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

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.

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, 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.

Objective To examine the prevalence of isolated IgA anti–β2-glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2GPI in a mouse model of thrombosis. Methods Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n = 558), patients with SLE from the Hopkins Lupus Cohort (n = 215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n = 5,098) were evaluated. IgA anti-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity. Results A total of 198 patients were found to be positive for IgA anti-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-β2GPI–positive serum samples reacted with domain IV/V of anti-β2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2GPI positivity was associated with an increased risk of arterial thrombosis (P < 0.001), venous thrombosis (P = 0.015), and all thrombosis (P < 0.001). The association between isolated IgA anti-β2GPI and arterial thrombosis (P = 0.0003) and all thrombosis (P = 0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. Conclusion Isolated IgA anti-β2GPI–positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid tests are negative and APS is suspected is recommended. IgA anti-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids.

Certain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia.To determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug.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.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.Any hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure.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.Prescription of interacting antimicrobial drugs to patients on sulfonylureas is very common, and is associated with substantial morbidity and increased costs.