title: The clinical and genetic features of COPD-asthma overlap syndrome.
abstract: Individuals with chronic obstructive pulmonary disease (COPD) and asthma are an important but poorly characterised group. The genetic determinants of COPD and asthma overlap have not been studied. The aim of this study was to identify clinical features and genetic risk factors for COPD and asthma overlap. Subjects were current or former smoking non-Hispanic whites or African-Americans with COPD. Overlap subjects reported a history of physician-diagnosed asthma before the age of 40 years. We compared clinical and radiographic features between COPD and overlap subjects. We performed genome-wide association studies (GWAS) in the non-Hispanic whites and African-American populations, and combined these results in a meta-analysis. More females and African-Americans reported a history of asthma. Overlap subjects had more severe and more frequent respiratory exacerbations, less emphysema and greater airway wall thickness compared to subjects with COPD alone. The non-Hispanic white GWAS identified single nucleotide polymorphisms in the genes CSMD1 (rs11779254, p=1.57 × 10(-6)) and SOX5 (rs59569785, p=1.61 × 10(-6)) and the meta-analysis identified single nucleotide polymorphisms in the gene GPR65 (rs6574978, p=1.18 × 10(-7)) associated with COPD and asthma overlap. Overlap subjects have more exacerbations, less emphysema and more airway disease for any degree of lung function impairment compared to COPD alone. We identified novel genetic variants associated with this syndrome. COPD and asthma overlap is an important syndrome and may require distinct clinical management.
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA remeh@channing.harvard.edu.
authors.forename: Megan
authors.initials: M
authors.lastname: Hardin
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Cho
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Merry-Lynn
authors.initials: ML
authors.lastname: McDonald
authors.affiliation: Dept of Epidemiology, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Beaty
authors.affiliation: Dept of Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Ramsdell
authors.affiliation: Dept of Pulmonary, Allergy and Critical Care Medicine, University of Alabama, Birmingham, AL, USA.
authors.forename: Surya
authors.initials: S
authors.lastname: Bhatt
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
authors.forename: Edwin J R
authors.initials: EJ
authors.lastname: van Beek
authors.affiliation: Dept of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Make
authors.affiliation: Dept of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hersh
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000150:complications* / Q000235:genetics; D015897:Comorbidity; D004646:Emphysema / Q000150:complications; D005260:Female; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000235:genetics; D013902:Radiography, Thoracic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014057:Tomography, X-Ray Computed