Wood smoke exposure and gene promoter methylation are associated with increased risk for COPD in smokers.
BACKGROUND
Wood smoke-associated chronic obstructive pulmonary disease (COPD) is common in women in developing countries but has not been adequately described in developed countries.


OBJECTIVE
Our objective was to determine whether wood smoke exposure was a risk factor for COPD in a population of smokers in the United States and whether aberrant gene promoter methylation in sputum may modify this association.


METHODS
For this cross-sectional study, 1,827 subjects were drawn from the Lovelace Smokers' Cohort, a predominantly female cohort of smokers. Wood smoke exposure was self-reported. Postbronchodilator spirometry was obtained, and COPD outcomes studied included percent predicted FEV₁, airflow obstruction, and chronic bronchitis. Effect modification of wood smoke exposure with current cigarette smoke, ethnicity, sex, and promoter methylation of lung cancer-related genes in sputum on COPD outcomes were separately explored. Multivariable logistic and poisson regression models were used for binary and rate-based outcomes, respectively.


RESULTS
Self-reported wood smoke exposure was independently associated with a lower percent predicted FEV₁ (point estimate [± SE] -0.03 ± 0.01) and a higher prevalence of airflow obstruction and chronic bronchitis (odds ratio, 1.96; 95% confidence interval, 1.52-2.52 and 1.64 (95% confidence interval, 1.31-2.06, respectively). These associations were stronger among current cigarette smokers, non-Hispanic whites, and men. Wood smoke exposure interacted in a multiplicative manner with aberrant promoter methylation of the p16 or GATA4 genes on lower percent predicted FEV₁.


CONCLUSIONS
These studies identify a novel link between wood smoke exposure and gene promoter methylation that synergistically increases the risk for reduced lung function in cigarette smokers.
Sood
Akshay
A
University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
Petersen
Hans
H
Blanchette
Christopher M
CM
Meek
Paula
P
Picchi
Maria A
MA
Belinsky
Steven A
SA
Tesfaigzi
Yohannes
Y
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D015987:Effect Modifier, Epidemiologic; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D005541:Forced Expiratory Volume; D050991:GATA4 Transcription Factor / Q000737:chemistry; D019942:Genes, p16 / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009516:New Mexico / Q000453:epidemiology; D010641:Phenotype; D011401:Promoter Regions, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology* / Q000503:physiopathology; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors; D012906:Smoke; D012907:Smoking / Q000453:epidemiology* / Q000208:ethnology / Q000503:physiopathology; D013147:Spirometry; D013183:Sputum / Q000737:chemistry / Q000502:physiology; D044465:White People / Q000208:ethnology / Q000235:genetics; D014934:Wood
D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D012906:Smoke