Epidemiology, radiology, and genetics of nicotine dependence in COPD

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Abstract

Background

Cigarette 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.

Methods

Current 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.

Results

Among 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.

Conclusions

Nicotine 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 registration

ClinicalTrials (NCT): NCT00608764

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Most cited references 29

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The natural history of chronic airflow obstruction.

C. Fletcher, R. Peto (1977)

A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).

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Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.

Christopher Amos, Xifeng Wu, Peter Broderick … (2008)

To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 x 10(-17)) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.

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The prediction of small airway dimensions using computed tomography.

W. Crawford Elliott, Yasutaka Nakano, Alfonso De Simone … (2005)

Chronic obstructive pulmonary disease is characterized by destruction of the lung parenchyma and/or small airway narrowing. To determine whether the dimensions of relatively large airways assessed using computed tomography (CT) reflect small airway dimensions measured histologically, we assessed these variables in nonobstructed or mild to moderately obstructed patients having lobar resection for a peripheral tumor. For both CT and histology, the square root of the airway wall area (Aaw) was plotted versus lumen perimeter to estimate wall thickness. The wall area percentage was calculated as wall area/lumen area + wall area x 100. Although CT overestimated Aaw, the slopes of the relationships between the square root of Aaw and internal perimeter (Pi) measured with both techniques were related (CT slope = 0.2059 histology slope + 0.1701, R2 = 0.32, p < 0.01). The mean wall area percentage measured by CT for airways with a Pi of greater than 0.75 cm predicted the mean dimensions of the small airways with an internal diameter of 1.27 mm (R2 = 0.57, p < 0.01). We conclude that CT measurements of airways with a Pi of 0.75 cm or more could be used to estimate the dimensions of the small conducting airways, which are the site of airway obstruction in chronic obstructive pulmonary disease.

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Author and article information

Journal

Journal ID (nlm-ta): Respir Res

Title: Respiratory Research

Publisher: BioMed Central

ISSN (Print): 1465-9921

ISSN (Electronic): 1465-993X

Publication date (Print): 2011

Publication date (Electronic): 13 January 2011

Volume: 12

Issue: 1

Page: 9

Affiliations

[1 ]Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA

[2 ]Division of Pulmonary and Critical Care Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea

[3 ]Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA

[4 ]Colorado School of Public Health, University of Colorado Denver, Aurora, USA

[5 ]Department of Radiology, National Jewish Health, Denver, CO, USA

[6 ]Department of Biostatistics, National Jewish Health, Denver, CO, USA

[7 ]Department of Medicine, National Jewish Health, Denver, CO, USA

Article

Publisher ID: 1465-9921-12-9

DOI: 10.1186/1465-9921-12-9

PMC ID: 3033825

PubMed ID: 21232152

SO-VID: be1dfd35-e1d8-481d-941b-7145878b52d8

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Epidemiology, radiology, and genetics of nicotine dependence in COPD

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Abstract

Background

Methods

Results

Conclusions

Trial registration

Related collections

Inflamed lung in vitro co-culture models

Most cited references 29

The natural history of chronic airflow obstruction.

Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.

The prediction of small airway dimensions using computed tomography.

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