Publications

Acad Radiol. 2010 Jan;17(1):48-53. Epub 2009 Sep 24.

Identification of early interstitial lung disease in smokers from the COPDGene Study.

Washko GR, Lynch DA, Matsuoka S, Ross JC, Umeoka S, Diaz A, Sciurba FC, Hunninghake GM, San José Estépar R, Silverman EK, Rosas IO, Hatabu H.

Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract

RATIONALE AND OBJECTIVES: The aim of this study is to compare two subjective methods for the identification of changes suggestive of early interstitial lung disease (ILD) on chest computed tomographic (CT) scans. MATERIALS AND METHODS: The CT scans of the first 100 subjects enrolled in the COPDGene Study from a single institution were examined using a sequential reader and a group consensus interpretation scheme. CT scans were evaluated for the presence of parenchymal changes consistent with ILD using the following scoring system: 0 = normal, 1 = equivocal for the presence of ILD, 2 = highly suspicious for ILD, and 3 = classic ILD changes. A statistical comparison of patients with early ILD to normal subjects was performed. RESULTS: There was a high degree of agreement between methods (kappa = 0.84; 95% confidence interval, 0.73-0.94; P < .0001 for the sequential and consensus methods). The sequential reading method had both high positive (1.0) and negative (0.97) predictive values for a consensus read despite a 58% reduction in the number of chest CT evaluations. Regardless of interpretation method, the prevalence of chest CT changes consistent with early ILD in this subset of smokers from COPDGene varied between 5% and 10%. Subjects with early ILD tended to have greater tobacco smoke exposure than subjects without early ILD (P = .053). CONCLUSIONS: A sequential CT interpretation scheme is an efficient method for the visual interpretation of CT data. Further investigation is required to independently confirm our findings and further characterize early ILD in smokers.

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Nat Genet. 2010 Mar;42(3):200-2. Epub 2010 Feb 21.

Variants in FAM13A are associated with chronic obstructive pulmonary disease.

Cho MH, Boutaoui N, Klanderman BJ, Sylvia JS, Ziniti JP, Hersh CP, DeMeo DL, Hunninghake GM, Litonjua AA, Sparrow D, Lange C, Won S, Murphy JR, Beaty TH, Regan EA, Make BJ, Hokanson JE, Crapo JD, Kong X, Anderson WH, Tal-Singer R, Lomas DA, Bakke P, Gulsvik A, Pillai SG, Silverman EK.

Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Abstract

We performed a genome-wide association study for chronic obstructive pulmonary disease (COPD) in three population cohorts, including 2,940 cases and 1,380 controls who were current or former smokers with normal lung function. We identified a new susceptibility locus at 4q22.1 in FAM13A and replicated this association in one case-control group (n = 1,006) and two family-based cohorts (n = 3,808) (rs7671167, combined P = 1.2 x 10(-11), combined odds ratio in case-control studies 0.76, 95% confidence interval 0.69-0.83).

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COPD. 2010 Feb;7(1):32-43.

Genetic epidemiology of COPD (COPDGene) study design.

Regan EA, Hokanson JE, Murphy JR, Make B, Lynch DA, Beaty TH, Curran-Everett D, Silverman EK, Crapo JD.

National Jewish Health, Denver, Colorado, USA. regane@njhealth.org

Abstract

BACKGROUND: COPDGene is a multicenter observational study designed to identify genetic factors associated with COPD. It will also characterize chest CT phenotypes in COPD subjects, including assessment of emphysema, gas trapping, and airway wall thickening. Finally, subtypes of COPD based on these phenotypes will be used in a comprehensive genome-wide study to identify COPD susceptibility genes. METHODS/RESULTS: COPDGene will enroll 10,000 smokers with and without COPD across the GOLD stages. Both Non-Hispanic white and African-American subjects are included in the cohort. Inspiratory and expiratory chest CT scans will be obtained on all participants. In addition to the cross-sectional enrollment process, these subjects will be followed regularly for longitudinal studies. A genome-wide association study (GWAS) will be done on an initial group of 4000 subjects to identify genetic variants associated with case-control status and several quantitative phenotypes related to COPD. The initial findings will be verified in an additional 2000 COPD cases and 2000 smoking control subjects, and further validation association studies will be carried out. CONCLUSIONS: COPDGene will provide important new information about genetic factors in COPD, and will characterize the disease process using high resolution CT scans. Understanding genetic factors and CT phenotypes that define COPD will potentially permit earlier diagnosis of this disease and may lead to the development of treatments to modify progression.

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