Background Cigarette smoking is a major risk factor for COPD and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a Dopamine Beta-Hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in COPD subjects. Methods GWAS were conducted in 4 independent cohorts encompassing 3,441 ever-smoking COPD subjects (GOLD stage II or higher). Untyped SNPs were imputed using HapMap (phase II) panel. Results from all cohorts were meta-analyzed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within alpha-nicotinic acetylcholine receptors 3/5 (CHRNA3/CHRNA5; e.g. p=0.00011 for SNP rs1051730) and Cytochrome P450 2A6 (CYP2A6; e.g. p=2.78×10−5 for a nonsynonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in the DBH was significantly (p=0.015) associated with smoking cessation. Conclusion We identified two candidate regions associated with age at smoking initiation in COPD subjects. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviors of COPD patients.

This is a retrospective evaluation of the incidence of aberrant subclavian arteries (ASAs) and diverticula of Kommerell, as well as the occurrence and significance of associated aneurysms. Thoracic aortograms obtained during a 12.5-year period were reviewed, seeking the presence of aberrant right and left subclavian arteries (ARSAs/ALSAs), diverticula of Kommerell, and the incidence of associated aortic aneurysms. Several cases were evaluated with computed tomography concomitantly. Results were correlated with a literature review. Twenty-two ASAs were identified. Nineteen were on the right (ARSAs) and three were on the left (ALSAs). A diverticulum of Kommerell (DOK) was also present on the right in seven and on the left in three. Five of these patients had complicating aneurysms. Four of these were associated with ARSAs and their diverticula. Two were atherosclerotic; one was a limited dissection and one of uncertain etiology was ruptured. One additional aneurysm (atherosclerotic) involved an ALSA/DOK. The patient with the ruptured aneurysm died in surgery; three were managed conservatively because of concomitant disease; and one is being followed because of the small size (2.5 cm) of the aneurysm. ARSAs are relatively uncommon and ALSAs are rare. Both ARSA and ALSA are frequently associated with a DOK. Aneurysms rarely involve ASAs (with or without a DOK), but they are associated with a high mortality rate if they are not discovered before rupture. Early diagnosis plus surgical and/or endovascular management can be lifesaving.

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Rationale: The demographic, physiological, and computed tomography (CT) features associated with pneumothorax in smokers with and without chronic obstructive pulmonary disease (COPD) are not clearly defined.Objectives: We evaluated the hypothesis that pneumothorax in smokers is associated with male sex, tall and thin stature, airflow obstruction, and increased total and subpleural emphysema. Methods:The study included smokers with and without COPD from the COPDGene Study, with quantitative chest CT analysis. Pleural-based emphysema was assessed on the basis of local histogram measures of emphysema. Pneumothorax history was defined by subject self-report.Measurements and Main Results: Pneumothorax was reported in 286 (3.2%) of 9,062 participants. In all participants, risk of prior pneumothorax was significantly higher in men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.08-2.22) and non-Hispanic white subjects (OR, 1.90; 95% CI, 1.34-2.69). Risk of prior pneumothorax was associated with increased percent CT emphysema in all participants and participants with COPD (OR, 1.04 for each 1% increase in emphysema; 95% CI, 1.03-1.06). Increased pleural-based emphysema was independently associated with risk of past pneumothorax in all participants (OR, 1.05 for each 1% increase; 95% CI, 1.01-1.10). In smokers with normal spirometry, risk of past pneumothorax was associated with non-Hispanic white race and lifetime smoking intensity (OR, 1.20 for every 10 pack-years; 95% CI, 1.09-1.33).Conclusions: Among smokers, pneumothorax is associated with male sex, non-Hispanic white race, and increased percentage of total and subpleural CT emphysema. Pneumothorax was not independently associated with height or lung function, even in participants with COPD.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).