Wood smoke exposure and gene promoter methylation are associated with increased risk for COPD in smokers

Am J Respir Crit Care Med. 2010 Nov 1;182(9):1098-104. doi: 10.1164/rccm.201002-0222OC. Epub 2010 Jul 1.


Rationale: Wood smoke-associated chronic obstructive pulmonary disease (COPD) is common in women in developing countries but has not been adequately described in developed countries.

Objectives: 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.

Measurements and main 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • DNA Methylation
  • Effect Modifier, Epidemiologic
  • Environmental Exposure / adverse effects*
  • Female
  • Forced Expiratory Volume
  • GATA4 Transcription Factor / chemistry
  • Genes, p16 / physiology
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • New Mexico / epidemiology
  • Phenotype
  • Promoter Regions, Genetic
  • Pulmonary Disease, Chronic Obstructive / epidemiology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Regression Analysis
  • Risk Factors
  • Sex Factors
  • Smoke
  • Smoking / epidemiology*
  • Smoking / ethnology
  • Smoking / physiopathology
  • Spirometry
  • Sputum / chemistry
  • Sputum / physiology
  • White People / ethnology
  • White People / genetics
  • Wood*


  • GATA4 Transcription Factor
  • GATA4 protein, human
  • Smoke