Severe alpha-1-antitrypsin deficiency is the only proven genetic risk factor for chronic obstructive pulmonary disease (COPD). We have assembled a cohort of 44 probands with severe, early-onset COPD, who do not have severe alpha-1-antitrypsin deficiency. A surprisingly high prevalence of females (79.6%) was found. Assessment of the risk to relatives of these early-onset COPD probands for airflow obstruction and chronic bronchitis was performed to determine whether significant familial aggregation for COPD, independent of alpha-1-antitrypsin deficiency, could be demonstrated. First- degree relatives of early-onset COPD probands had significantly lower FEV1 and FEV1/FVC values than control subjects (p < 0.01), despite similar pack-years of smoking. Reduced spirometric values in first-degree relatives of early-onset COPD probands were found only in current or ex-cigarette smokers. The mean FEV1 in current or ex-smoking first-degree relatives was 76.1 +/- 20.9% predicted compared to 89.2 +/- 14.4% predicted in current or ex-smoking control subjects (p < 0.01); in lifelong nonsmokers, the mean FEV1 was 93.4% predicted for both control subjects and first-degree relatives of early-onset COPD probands. Generalized estimating equations, adjusting for age and pack-years of smoking, demonstrated increased odds of reduced FEV1 and chronic bronchitis in current or ex-smoking first-degree relatives of early-onset COPD probands. Using a new method to estimate relative risk from relative odds, we estimate that the relative risks for FEV1 below 60%, FEV1 below 80%, and chronic bronchitis are each approximately three in current or ex-smoking first-degree relatives of early-onset COPD probands. The increased risk to relatives of early-onset COPD probands for reduced FEV1 and chronic bronchitis, limited to current or ex-smokers, suggests genetic risk factor(s) for COPD that are expressed in response to cigarette smoking.

BACKGROUND: Readmission following hospital discharge has become an important target of quality improvement. OBJECTIVE: To describe the development, validation, and results of a risk‐standardized measure of hospital readmission rates among elderly patients with pneumonia employed in federal quality measurement and efficiency initiatives. DESIGN: A retrospective cohort study using hospital and outpatient Medicare claims from 2005 and 2006. SETTING: A total of 4675 hospitals in the United States. PATIENTS: Medicare beneficiaries aged >65 years with a principal discharge diagnosis of pneumonia. INTERVENTION: None. MEASUREMENTS: Hospital‐specific, risk‐standardized 30‐day readmission rates calculated as the ratio of predicted‐to‐expected readmissions, multiplied by the national unadjusted rate. Comparison of the areas under the receiver operating curve (ROC) and measurement of correlation coefficient in development and validation samples. RESULTS: The development sample consisted of 226,545 hospitalizations at 4675 hospitals, with an overall unadjusted 30‐day readmission rate of 17.4%. The median risk‐standardized hospital readmission rate was 17.3%, and the odds of readmission for a hospital one standard deviation above average was 1.4 times that of a hospital one standard deviation below average. Performance of the medical record and administrative models was similar (areas under the ROC curve 0.59 and 0.63, respectively) and the correlation coefficient of estimated state‐specific standardized readmission rates from the administrative and medical record models was 0.96. CONCLUSIONS: Rehospitalization within 30 days of treatment for pneumonia is common, and rates vary across hospitals. A risk‐standardized measure of hospital readmission rates derived from administrative claims has similar performance characteristics to one based on medical record review. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine