Abstract
BackgroundCigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers.MethodsCurrent smokers with COPD (GOLD stage ≥ 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes.ResultsAmong 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p < .0001) as well as in COPD cases (ρ = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers.ConclusionsNicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.Trial registrationClinicalTrials (NCT): NCT00608764
Highlights
Cigarette smoking is the most important environmental risk factor for the development of COPD [1,2,3]
COPD subjects were older in age, and white race was more common among COPD cases
Mean FTND score, percentage of cases with high nicotine dependence (FTND score ≥6), the age started smoking, and the current number of cigarettes smoked daily were not different between COPD cases and control subjects, the total amount of smoking in pack-years and average number of cigarettes smoked per day were higher in COPD subjects
Summary
Cigarette smoking is the most important environmental risk factor for the development of COPD [1,2,3]. Cigarette smoking intensity is known to be associated with clinical features of COPD such as the rate of lung function decline [2,4] and COPD exacerbation frequency [5,6]. It is correlated with symptoms of chronic bronchitis even in healthy smokers [7]. The extent of trapping determined by quantitative analysis of chest CT scans These radiographic measurements have been correlated with respiratory symptoms and physiologic parameters [12,13]. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers
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