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Rationale: Genomic regions identified by genome-wide association studies explain only a small fraction of heritability for chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin deficiency shows that rare coding variants of large effect also influence COPD susceptibility. We hypothesized that exome sequencing in families identified through a proband with severe, early-onset COPD would identify additional rare genetic determinants of large effect.Objectives: To identify rare genetic determinants of severe COPD.Methods: We applied filtering approaches to identify potential causal variants for COPD in whole exomes from 347 subjects in 49 extended pedigrees from the Boston Early-Onset COPD Study. We assessed the power of this approach under different levels of genetic heterogeneity using simulations. We tested genes identified in these families using gene-based association tests in exomes of 204 cases with severe COPD and 195 resistant smokers from the COPDGene study. In addition, we examined previously described loci associated with COPD using these datasets.Measurements and Main Results: We identified 69 genes with predicted deleterious nonsynonymous, stop, or splice variants that segregated with severe COPD in at least two pedigrees. Four genes (DNAH8, ALCAM, RARS, and GBF1) also demonstrated an increase in rare nonsynonymous, stop, and/or splice mutations in cases compared with resistant smokers from the COPDGene study; however, these results were not statistically significant. We demonstrate the limitations of the power of this approach under genetic heterogeneity through simulation.Conclusions: Rare deleterious coding variants may increase risk for COPD, but multiple genes likely contribute to COPD susceptibility. [ABSTRACT FROM AUTHOR]

Information about several papers discusses at the International COPD Genetics Consortium held in Boston, Massachusetts from July 13 to 14, 2010 is presented. Topics included the genomic technology and techniques for chronic obstructive pulmonary disease (COPD). The event featured several physicians including Wayne Anderson.

BACKGROUND: Prolonged mechanical ventilation and home ventilation impose unique challenges on patients, families, and the healthcare system. In the absence of a centralized database to track prolonged and home ventilation, there has been a paucity of prevalence studies, and what is known is outdated. We surveyed respiratory care managers working in the state of Massachusetts to estimate the prevalence and locations of prolonged and home ventilation in 2006. METHODS: We invited 113 respiratory care managers practicing in acute-care hospitals, long-term acute-care facilities (also known as weaning units, step-down units, and long-term-ventilation units), and home-care companies to participate in a Web-based survey. We matched the responses to their respective institutions and analyzed the results according to hospital size, location (urban or suburban), and whether the institution was a teaching institution. RESULTS: In December of 2006 there were 817 ventilated patients, of whom 460 met the criteria for prolonged ventilation (> 21 d for at least 6 h/d) and 221 met the criteria for home ventilation (ventilation for any period of time at home). Of the 239 patients not at home, 64 were in acute-care hospitals, 175 in long-term acute-care facilities, and 221 at home. The survey response rate was 86% for acute-care hospitals with ≥ 400 beds, 48% for acute-care hospitals with < 400 beds, 65% for long-term acute-care facilities, and 67% for home-care companies. The non-respondents were primarily smaller, suburban, non-teaching hospitals, which have a low prevalence of prolonged-ventilation patients. Among the home-ventilation patients, the majority had neuromuscular diseases, were < 65 years old, and were ventilated via tracheostomy tube. The most important limitations to transitioning prolonged-ventilation patients to home ventilation appeared to be lack of family and/or economic support. CONCLUSIONS: In Massachusetts, the estimated prevalence of prolonged and home ventilation increased from 2.8/100,000 inhabitants in 1983 to 7.1/100,000 inhabitants in 2006, and the majority of them are in long-term acute-care facilities, large urban teaching hospitals, and at home. [ABSTRACT FROM AUTHOR]