īoth COPD and asthma are heritable diseases with known genetic risk factors. In recognition of this important subset of patients, the Spanish, Canadian and Japanese respiratory societies have recently included the identification and management of these subjects in their COPD guidelines. Despite this, there is growing evidence that subjects with both COPD and asthma represent an important and distinct patient population, with worse clinical features than those with COPD alone. The dual diagnosis of COPD and asthma is often an exclusion criterion in most studies investigating these diseases individually, limiting the large-scale cohorts available for investigation. However, few studies have investigated the clinical features of this overlap syndrome, and none have investigated the genetics of this syndrome. The presence of asthma among subjects with chronic obstructive pulmonary disease (COPD) is well recognised, and up to 24% of patients with COPD will additionally report a history of asthma. COPD and asthma overlap is an important syndrome and may require distinct clinical management. We identified novel genetic variants associated with this syndrome. Overlap subjects have more exacerbations, less emphysema and more airway disease for any degree of lung function impairment compared to 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 had more severe and more frequent respiratory exacerbations, less emphysema and greater airway wall thickness compared to subjects with COPD alone. More females and African–Americans reported a history of asthma. We performed genome-wide association studies (GWAS) in the non-Hispanic whites and African–American populations, and combined these results in a meta-analysis. We compared clinical and radiographic features between COPD and overlap subjects. Overlap subjects reported a history of physician-diagnosed asthma before the age of 40 years. Subjects were current or former smoking non-Hispanic whites or African–Americans with COPD. The aim of this study was to identify clinical features and genetic risk factors for COPD and asthma overlap. The genetic determinants of COPD and asthma overlap have not been studied.

Individuals with chronic obstructive pulmonary disease (COPD) and asthma are an important but poorly characterised group.

Continental Drift by James D. Houston