The present study shows that exposure to wood smoke is associated with all COPD phenotypes studied (i.e., low lung function, airflow obstruction, and chronic bronchitis) in a cohort of smokers living in an urban area of southwestern United States, independent of cigarette smoking. These associations are stronger among current cigarette smokers, non-Hispanic whites, and men, as compared with former cigarette smokers, Hispanics, and women, respectively. In addition, smokers with aberrant promoter methylation of the p16 and GATA4 genes in sputum demonstrate stronger associations between wood smoke exposure and lower lung function than those without these epigenetic changes.
In developed countries, people are exposed to wood smoke in a variety of ways, including smoke from residential heating, cooking stoves, campfires, forest fires, and prescribed fires (17
). Wood burning is an important contributor to particle and gaseous material in ambient air and in some locations accounts for up to 80% of the airborne particle concentrations during the winter (18
). Measurements in homes heated with wood show that the total particulate matter concentrations range from 0.05 to 0.1 mg/m3
). Wood burning not only increases indoor but also outdoor “neighborhood” pollution, thereby exposing many nonusers to wood smoke components (20
). Based on seasonal variations in particulate matter of median aerometric diameter less than 2.5 μm (PM2.5
), the local air agency confirmed that wood smoke may be an important contributor to the pollution in the Albuquerque area. Wood smoke is a complex mixture of numerous volatile and particulate substances constituted by different organic and inorganic compounds known to be toxic or irritating to the respiratory system. Its composition varies with the wood type and the conditions of combustion. More than 200 chemical and compound groups have been identified in wood smoke, most of which are in the inhalable size range, generally smaller than 1 μm (21
), and often include ultrafine particles (< 100 μm). Exposure to wood smoke in developed countries tends to be at sustained low levels, unlike exposure to cigarette smoke, which is short-term but intense, with a single cigarette introducing 15 to 40 mg total particulate matter into the respiratory tract.
Our study contrasts with most studies conducted outside the United States that have focused on nonsmokers. Our population of relatively older smokers may be particularly susceptible to the adverse respiratory effects of wood smoke exposure, compared with the general population. This conclusion is supported by the observed additive effect between current cigarette smoke and wood smoke exposures on COPD phenotypes. Furthermore, these epidemiological findings are substantiated by our laboratory findings in which pulmonary inflammation and pathological changes were enhanced in mice concurrently exposed to wood smoke and cigarette smoke compared with cigarette smoke alone (Y. Tesfaigzi, unpublished observations).
Our findings that New Mexican non-Hispanic whites are at greater risk for wood smoke–associated COPD than Hispanics is generally consistent with previous studies by our group and others showing that non-Hispanic whites in New Mexico may be at greater risk for COPD (22
). Although the bases for these findings are not known, possible explanations include ethnic differences in the metabolism of wood smoke products, genetic susceptibility to the effects of wood smoke, type of wood burnt in homes, and prevalence of obesity.
Our study suggests that men may be at higher risk than women with respect to wood smoke–associated COPD. This may reflect the fact that men may have greater involvement with loading, lighting, and maintaining wood stoves than women do in developed countries, resulting in greater wood smoke exposure.
Aberrant promoter methylation of genes in sputum of smokers was associated with various COPD phenotypes, particularly with reduced lung function. The majority of participants with COPD phenotypes in our cohort have mild to moderate (Stage I and II) disease based on the GOLD criteria. The observed association between high methylation index in sputum and reduced pulmonary function suggests that gene promoter methylation in sputum may be an early biomarker for COPD. However, additional longitudinal studies, including those using COPD phenotypes defined by high-resolution computed tomography, are needed to confirm this hypothesis.
In this study, we report a synergistic association for lower lung function between wood smoke exposure and aberrant promoter methylation of the p16 and GATA4 genes in the sputum of smokers. We did not find that promoter methylation caused or explained away the wood smoke association. However, wood smoke and promoter methylation were independent predictors of low lung function. GATA4 is a transcriptional regulator of numerous cell cycle genes (25
), and p16 mediates cell cycle arrest and senescence (26
), suggesting that these pathways may be disrupted during the development of COPD. Each of these variables (i.e., low lung function 
, wood smoke exposure 
, and methylation of the above-mentioned genes ) are independently associated with increased risk for lung cancer. Therefore, one would postulate that exposure to wood smoke may enhance the risk for aberrant gene promoter methylation and the development of lung cancer in cigarette smokers. Due to the large number of people exposed to wood smoke worldwide, this hypothesis has great public health importance and needs further investigation.
The strengths of our study include its analysis of interactions between wood smoke exposure and cigarette smoke exposures, ethnicity, sex, and epigenetic changes in sputum on COPD outcomes. Additional strengths include use of postbronchodilator spirometry to define obstruction, strict adherence to the 1994 ATS guidelines in the performance of spirometry, the use of NHANES III reference standards, and the fact that similar results were obtained whether a fixed ratio (i.e., FEV1
/FVC < 70%) or a statistically defined lower limit of FEV1
/FVC ratio (29
) was used to define obstruction (16
We recognize several limitations to our study. We cannot exclude differences in α-1 antitrypsin deficient status as an alternative explanation to our findings. However, severe α-1 antitrypsin deficiency accounts for only 1 to 2% of cases of COPD. Our study cohort may not be representative of all smokers in New Mexico and in other parts of the United States. However, the smoking behavior in this study is consistent with that observed in representative surveys of the state of New Mexico (30
). Finally, obtaining a binary exposure variable, based on whether or not subjects were exposed to wood smoke from a self-report, overlooks the potential for large variability of exposures and could introduce information bias. We recognize the need to better measure exposure to wood smoke constituents by validated questionnaire instruments or home exposure monitoring devices to obtain the type, unit amount, and duration of wood smoke the people are exposed to. Therefore, additional research on wood smoke–associated COPD should be performed in cigarette smokers with particular emphasis on understanding the characteristics and dose–response relationship of wood smoke exposure. Although DNA methylation is generally considered to be a stable epigenetic mark, longitudinal studies need to establish the stability of the epigenetic changes in sputum DNA. Furthermore, we analyzed genes that are believed to be primarily associated with lung cancer. Future studies designed to identify genes methylated specifically in COPD are necessary to develop better biomarkers for this disease. Having successfully established a mouse model that shows enhanced inflammation when exposed to cigarette and wood smoke compared with cigarette or wood smoke alone, studies on identifying epigenetic changes in DNA isolated from murine lung cells will help identify the genes modified by cigarette and wood smoke exposure.