Trisha M. Parekh

the development of curative and regenerative therapies that go beyond the largely symptomatic treatment options available; and (6) deployment of public health preventive strategies for banning smoking and maintaining clean air. We are fully cognisant that the scientific evidence to support some of our proposals is lacking. However, it is the intention of the Commission to generate discourse and debate, catalyse momentum, and provide a much-needed new vision to set the course towards the elimination of COPD.

BACKGROUND: ), 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: > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. RESULTS: 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.

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.

Abstract Rationale African American individuals have worse outcomes in chronic obstructive pulmonary disease (COPD). Objectives To assess whether race-specific approaches for estimating lung function contribute to racial inequities by failing to recognize pathological decrements and considering them normal. Methods In a cohort with and at risk for COPD, we assessed whether lung function prediction equations applied in a race-specific versus universal manner better modeled the relationship between FEV1, FVC, and other COPD outcomes, including the COPD Assessment Test, St. George’s Respiratory Questionnaire, computed tomography percent emphysema, airway wall thickness, and 6-minute-walk test. We related these outcomes to differences in FEV1 using multiple linear regression and compared predictive performance between fitted models using root mean squared error and Alpaydin’s paired F test. Measurements and Main Results Using race-specific equations, African American individuals were calculated to have better lung function than non-Hispanic White individuals (FEV1, 76.8% vs. 71.8% predicted; P = 0.02). Using universally applied equations, African American individuals were calculated to have worse lung function. Using Hankinson’s Non-Hispanic White equation, FEV1 was 64.7% versus 71.8% (P &amp;lt; 0.001). Using the Global Lung Initiative’s Other race equation, FEV1 was 70.0% versus 77.9% (P &amp;lt; 0.001). Prediction errors from linear regression were less for universally applied equations compared with race-specific equations when examining FEV1% predicted with the COPD Assessment Test (P &amp;lt; 0.01), St. George’s Respiratory Questionnaire (P &amp;lt; 0.01), and airway wall thickness (P &amp;lt; 0.01). Although African American participants had greater adversity (P &amp;lt; 0.001), less adversity was only associated with better FEV1 in non-Hispanic White participants (P for interaction = 0.041). Conclusions Race-specific equations may underestimate COPD severity in African American individuals.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

OBJECTIVE: To examine the prevalence of isolated IgA anti-β2 -glycoprotein I (anti-β2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-β2 GPI 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-β2 GPI titers and binding to domain IV/V of β2 GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti-β2 GPI 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-β2 GPI isotype, and 57 patients were positive exclusively for IgA anti-β2 GPI 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-β2 GPI-positive serum samples reacted with domain IV/V of anti-β2 GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2 GPI 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-β2 GPI 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-β2 GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls. CONCLUSION: Isolated IgA anti-β2 GPI-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-β2 GPI antibodies directed to domain IV/V of β2 GPI represent an important subgroup of clinically relevant antiphospholipids.