TY - JOUR
T1 - The clinical and genetic features of COPD-asthma overlap syndrome
AU - Hardin, Megan
AU - Cho, Michael
AU - McDonald, Merry Lynn
AU - Beaty, Terri
AU - Ramsdell, Joe
AU - Bhatt, Surya
AU - Van Beek, Edwin J.R.
AU - Make, Barry J.
AU - Crapo, James D.
AU - Silverman, Edwin K.
AU - Hersh, Craig P.
PY - 2014/8/1
Y1 - 2014/8/1
N2 - 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.
AB - 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.
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U2 - 10.1183/09031936.00216013
DO - 10.1183/09031936.00216013
M3 - Article
C2 - 24876173
AN - SCOPUS:84905660075
SN - 0903-1936
VL - 44
SP - 341
EP - 350
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 2
ER -