Hans Petersen

Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States

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Publications (45)146.22 Total impact

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    ABSTRACT: Gene methylation is an epigenetic change that involves a heritable modification of chromatin structure that alters gene expression without a change in DNA sequence. It has previously been shown that methylation of the GATA-4 gene promoter region in sputum DNA is associated with low lung function and increased odds of chronic obstructive pulmonary disease (COPD) among smokers. Given these findings, we hypothesized that GATA-4 gene methylation in sputum DNA would be associated with low health status, as measured by the St. George's Respiratory Questionnaire (SGRQ), in subjects with COPD. Self-reported SGRQ, spirometry, and induced sputum samples were obtained from 168 COPD subjects from the Lovelace Smokers Cohort. GATA-4 gene methylation was evaluated in sputum DNA using nested methylation-specific polymerase chain reaction (PCR) assays. Using general linear model with Poisson regression, we found that GATA-4 gene methylation was significantly associated with overall lower SGRQ health status (parameter estimate = .296, p < .001). This finding remained significant even after controlling for age, lung function, and other covariates. In an additional analysis using logistic regression and comparing extreme tertiles of overall SGRQ score, we confirmed that GATA-4 gene methylation was associated with a 3-fold increase in risk of poor health status (OR 2.95 and p = .028). The unexplored links between epigenetic changes and psychosocial factors such as health status are critical gaps in the literature. This study is the first to suggest that airway GATA-4 gene methylation status may independently predict health status in individuals with COPD.
    Biological Research for Nursing 06/2014; · 1.85 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 04/2014; 189(7):871. · 11.04 Impact Factor
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    ABSTRACT: Chronic mucous hypersecretion (CMH) contributes to COPD exacerbations and increased risk for lung cancer. Because methylation of gene promoters in sputum has been shown to be associated with lung cancer risk, we tested whether such methylation was more common in persons with CMH. Eleven genes commonly silenced by promoter methylation in lung cancer and associated with cancer risk were selected. Methylation specific PCR (MSP) was used to profile the sputum of 900 individuals in the Lovelace Smokers Cohort (LSC). Replication was performed in 490 individuals from the Pittsburgh Lung Screening Study (PLuSS). CMH was significantly associated with an overall increased number of methylated genes, with SULF2 methylation demonstrating the most consistent association. The association between SULF2 methylation and CMH was significantly increased in males but not in females both in the LSC and PLuSS (OR = 2.72, 95 % CI = 1.51-4.91, p = 0.001 and OR = 2.97, 95 % CI = 1.48-5.95, p = 0.002, respectively). Further, the association between methylation and CMH was more pronounced among 139 male former smokers with persistent CMH compared to current smokers (SULF2; OR = 3.65, 95 % CI = 1.59-8.37, p = 0.002). These findings demonstrate that especially male former smokers with persistent CMH have markedly increased promoter methylation of lung cancer risk genes and potentially could be at increased risk for lung cancer.
    Respiratory research 01/2014; 15(1):2. · 3.64 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) has been the only leading cause of death associated with a continuously increasing trend in the US over the past 30 years.
    SpringerPlus 01/2014; 3:359.
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    ABSTRACT: Rationale: The literature on the effect of obesity and weight gain on respiratory outcomes in smokers is contradictory. Objective: To examine the cross-sectional effect of body mass index (BMI) and longitudinal effect of change in BMI upon spirometry and health status among smokers at risk for and with milder COPD. Methods and Measurements: Participants from the Lovelace Smokers' Cohort were followed for a median period of 6 years - 75% of whom were at risk and 25% had COPD at baseline examination. BMI and gain in BMI were examined as continuous independent variables, both overall and after stratification into three categories - normal-weight; overweight; and obese, based on baseline weight. Spirometry and health status (as assessed by St. George Respiratory Questionnaire total and subscale scores) were dependent variables. Covariates included age, sex, ethnicity, pack-years of smoking, and current smoking status. Cross-sectional analysis used linear and logistic regression while longitudinal analysis used mixed model approach. Main Results: In cross-sectional analyses, higher BMI was associated with worse health status among obese but better health status among normal-weight smokers. In longitudinal analyses, weight gain was associated with decrease in FEV1 and health status among obese smokers but an increase in these outcomes among normal-weight smokers. Conclusions: Weight gain affects respiratory outcomes differently between obese and normal-weight smokers. While FEV1 and health status decrease with weight gain among obese smokers, they improve among normal-weight smokers. The non-linear relationship between weight gain and respiratory outcomes suggests that this effect of excess weight is unlikely to be mechanical alone.
    American Journal of Respiratory and Critical Care Medicine 11/2013; · 11.04 Impact Factor
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    ABSTRACT: Cigarette smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD) in the United States. Host factors that influence rapid rate of FEV1 decline in smokers and how decline rate influences risk for developing COPD are unknown. Characterize the rate of FEV1 decline in ever-smokers, compare the risk of incident COPD between rapid decliners and others, and determine the effect of selected drugs on rapid decline. A total of 1,170 eligible ever-smokers from the longitudinal Lovelace Smokers Cohort with repeat spirometry tests over a minimum follow-up period of 3 years (mean follow-up: 5.9 years) were examined, including 809 ever-smokers without baseline spirometric abnormality. Longitudinal absolute decline in postbronchodilator FEV1 obtained from the slope defined by the spirometric values over all examinations was annualized and classified as 'rapid' (≥30 ml/year), 'normal' (0 to -29.9 ml/year) or 'no' decline (>0 ml/year). Logistic regression and Kaplan-Meir survival curves were used for analysis. Approximately 32% of ever-smokers exhibited rapid decline. Among ever-smokers without baseline spirometric abnormality, rapid decline was associated with increased risk for incident COPD [OR 1.88; p = 0.003]. The use of angiotensin converting enzyme (ACE) inhibitor at baseline examination was protective against rapid decline, particularly among those with co-morbid cardiovascular disease, hypertension, or diabetes [OR 0.48; 0.48 and 0.12 respectively; p≤ 0.02 for all analyses]. Ever-smokers with rapid decline in FEV1 are at higher risk for developing COPD. Use of ACE inhibitors by smokers may protect against 'rapid' decline and progression to COPD.
    Chest 09/2013; · 5.85 Impact Factor
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    ABSTRACT: The BODE index was developed as a prognostic mortality risk tool for persons with chronic obstructive pulmonary disease (COPD). It incorporates 4 measures: body mass index, lung obstruction, dyspnea, and exercise capacity. The intent of this study was to examine how well a BODE-like index constructed using a simpler lung function measure, peak expiratory flow, in combination with physical functioning and symptom information more readily found in survey data (a quasi-BODE index), performs in identifying persons at higher risk of mortality and whether it may be extended as an assessment of mortality risk to persons without diagnosed COPD. Using US national survey data from the Health Retirement Study for 2006-2010, each unit increase in the quasi-BODE index score was associated with a multiplicative 50% increase in mortality risk (odds ratio = 1.50, 95% confidence interval: 1.41, 1.59). The quasi-BODE index is a multidimensional health status instrument based on the BODE index, which is a good predictor of mortality. The quasi-BODE index was compiled using simple measures of physical and respiratory function. It is a potentially useful prognostic instrument for older adult populations with or without COPD, including those with severe physical limitations, particularly when combined with demographic factors and comorbid conditions.
    American journal of epidemiology 08/2013; · 5.59 Impact Factor
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    ABSTRACT: Objectives: Asthma exacerbations have well-established clinical and economic impact, yet lack consensus on characterization of an episode's severity. Asthma treatment guidelines outline the concept of a moderate asthma exacerbation, however, a clear definition that can be operationalized has not been proposed. Methods: Adult asthma (ICD-9: 493.XX) patients, with at least 9 months of continuous enrollment in the Fallon Community Health Plan were included in the retrospective cohort study. Patients diagnosed with COPD or other lower respiratory tract conditions were excluded. The first reported asthma-related event following a 2-week symptom-free period was designated as the index event. Asthma-related events were categorized as: 1) moderate exacerbations (symptom-based), or 2) severe exacerbations (claims-based). Timing between and temporal sequence of asthma-related events along with average costs were calculated. Results: Of 3,126 eligible patients, 55% reported an asthma-related event followed by a recurrent event(s). Moderate exacerbations followed by recurrent moderate exacerbations were most frequent (20%) with the shortest interval between exacerbations (mean: 83 days [SD 87]). Moderate exacerbations followed by severe exacerbations occurred in 16% of patients with an average of 176.74 (SD 176.94) days between events. Conclusions: Patient report of asthma bothersome enough to initiate contact with a clinician, but not requiring oral corticosteriod (OCS), is a definition for a moderate exacerbation that can be operationalized for research purposes. Further work is needed to demonstrate whether identification of moderate exacerbations will allow intervention that impacts the frequency and timing of future exacerbations.
    Journal of Asthma 03/2013; · 1.85 Impact Factor
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    Journal of clinical outcomes management: JCOM 02/2013; 20(2):60-68.
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    ABSTRACT: BACKGROUND: National asthma treatment guidelines recommend either the use of inhaled corticosteroids (ICS) or ICS in combination with a long-acting bronchodilator for the treatment of moderate to severe asthma. Even though asthma is common among older adults, few studies have assessed the differences in effectiveness between these two recommended therapies in patients over 65 years of age. OBJECTIVE: The aim of this study was to assess the association of the fluticasone-salmeterol combination (FSC) or ICS initiation on asthma-related events in Medicare-eligible asthma patients. METHODS: This was a retrospective observational study using a large health claims database (July 1, 2001 to June 30, 2008). Subjects 65 to 79 years of age with 12-month preindex and 3- to 12-month postindex eligibility, an asthma diagnosis (ICD-493.xx), and with 1 or more FSC or ICS claims at index were included. Subjects with an FSC or ICS claim in the preindex and any claim for chronic obstructive pulmonary disease were excluded. Subjects were observed until they had an event (emergency department [ED] inpatient hospitalization [IP], combined IP/ED or oral corticosteroid [OCS] use) or were no longer eligible in the database, whichever came first. Cox proportional hazards regression was used to assess risk of an asthma-related event (IP, ED, or IP/ED). Baseline characteristics (age, sex, region, index season, comorbidities, preindex use of short-acting β-agonists, OCS, other asthma controllers, and asthma-related ED/IP visits) were independent covariates in the model. RESULTS: A total of 10,837 met the criteria (4843 ICS and 5994 FSC). Age (70.4 and 70.5 years, respectively) and the percentage of female subjects (65.5% and 64.8%, respectively) were similar. Asthma-related events were also similar at baseline. Postindex unadjusted rates occurring after >30 days were ED (1.8% vs 1.5%, P = 0.18), IP (2.7% vs 1.7%, P < 0.001), and ED/IP (4.1% vs 2.8%, P < 0.001) for ICS and FSC, respectively. Subjects who received FSC were associated with a 32% (adjusted HR = 0.68; 95% CI, 0.51-0.91) lower risk of experiencing an IP visit and a 22% (HR = 0.78; 95% CI, 0.62-0.98) lower risk of experiencing an ED/IP visit. No differences were observed for ED visits (HR = 0.94; 95% CI, 0.68-1.29). CONCLUSIONS: In Medicare-eligible asthma patients, FSC use was associated with lower rates of asthma-related serious exacerbations compared with ICS.
    The American journal of geriatric pharmacotherapy. 10/2012;
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    ABSTRACT: Latent variable mixture modeling is becoming increasingly popular in nursing research, in part due to the sophistication of the method in identifying relationships, patterns, and clusters in the data. The aim of this study was to provide an overview of mixture modeling techniques, specifically as applied to nursing research, and to present examples from two studies to illustrate how these techniques may be used cross-sectionally and longitudinally. The first data example demonstrates the use of latent profile analysis as applied to the St. George respiratory symptoms questionnaire in 2,232 smokers from the Lovelace Smokers Cohort. The second data example demonstrates growth mixture modeling as applied to condom use trajectories among 728 at-risk adolescents on probation. Three classes of symptoms emerged among the smokers cohort: those who were high on all symptoms, those who were low on all symptoms, and those who were high on cough and phlegm only. These classes were then distinguishable by participant gender and wood smoke exposure. In the second data example, four classes of condom use emerged. Only 59% of the sample indicated the previously reported decline in condom use over time; condom use remained stable or significantly increased for the remaining 41%. Both sets of results provide additional substantive information about patterns in the data that were not apparent from previously applied traditional methodological techniques. Considerations for the use of latent variable mixture modeling in nursing research are discussed.
    Nursing research 05/2012; 61(3):204-12. · 1.80 Impact Factor
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    ABSTRACT: The epigenetic basis for human asthma is not well studied, particularly among older adults. This study investigated the methylation profiles in sputum DNA among older adults with asthma, using a population of smokers. This was a cross-sectional study using the Lovelace Smokers Cohort, a population of former and current smokers aged ≥ 40 years in New Mexico. One hundred eighty-four smokers with asthma were compared with 511 smoker control subjects with a similar smoking history, after carefully excluding those with COPD. Environmental exposures were assessed by a standard questionnaire. Postbronchodilator spirometry was performed. Induced sputum was analyzed for the methylation prevalence of 12 selected asthma-related genes using nested methylation-specific polymerase chain reaction assay. Asthma was associated with a greater number of methylated genes and, specifically, with methylated protocadherin-20 gene in sputum DNA compared with control subjects with a similar smoking history. These associations remained significant after adjustment for covariates as well as Bonferroni correction. A synergistic interaction was noted between two methylated genes (protocadherin-20 and paired box protein transcription factor-5α) in sputum DNA on the odds for asthma (P = .009). Interestingly, the epigenetic-asthma associations were not explained by the environmental factors studied. Further, methylated genes in sputum DNA, including the protocadherin-20 gene, identified a symptomatically more severe asthma phenotype in a subgroup analysis. Asthma is associated with methylation of selected genes, such as protocadherin-20 gene, in sputum DNA. If future studies establish causality, novel demethylating interventions to prevent and treat asthma among older smokers may be possible.
    Chest 02/2012; 142(2):425-31. · 5.85 Impact Factor
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    ABSTRACT: To compare the effectiveness of budesonide/formoterol fumarate dihydrate (BFC) and fluticasone propionate/salmeterol (FSC), two combination inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) products approved for the treatment of chronic obstructive pulmonary disease (COPD) in the US with respect to cost, therapy adherence, and related healthcare utilization. The effectiveness of these two treatments has not previously been compared in a US COPD population. A retrospective cohort study assessed COPD-related outcomes using administrative claims data among ICS/LABA-naïve patients. Patients initiating BFC were propensity matched to FSC patients. Cost and effectiveness were measured as total healthcare expenditures, exacerbation events (hospitalizations, emergency department visits, or outpatient visits associated with oral corticosteroid or antibiotic prescription fills), and treatment medication adherence. Differences in COPD symptom control were assessed via proxy measure through claims for rescue medications and outpatient encounters. Of the 6770 patients (3385 BFC and 3385 FSC), fewer BFC patients had claims for short-acting beta agonists (SABA) (34.7% vs 39.5%; p<0.001) and ipratropium (7.8% vs 9.8%, p<0.005) than FSC patients, but no substantial differences were seen in other clinical outcomes including tiotropium or nebulized SABA claims, COPD-related outpatient visits, or exacerbation events. There were no significant differences in total COPD-related medical costs in the 6-month period after initiation of combination therapy. This was a retrospective observational study using claims data and accuracy of COPD diagnoses could not be verified, nor was information available on severity of disease. The results and conclusions of this study are limited to the population observed and the operational definitions of the study variables. For most outcomes of interest, BFC and FSC showed comparable real-world effectiveness.
    Journal of Medical Economics 09/2011; 14(6):769-76.
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    ABSTRACT: The epidemiology of cigarette smoking-related chronic obstructive pulmonary disease (COPD) is not well characterized in Hispanics in the United States. Understanding how ethnicity influences COPD is important for a number of reasons, from informing public health policies to dissecting the genetic and environmental effects that contribute to disease. The present study assessed differences in risk between Hispanics and non-Hispanic whites for longitudinal and cross-sectional COPD phenotypes. Genetic ancestry was used to verify findings based on self-reported ethnicity. Hispanics in New Mexico are primarily differentiated from non-Hispanic whites by their proportion of Native American ancestry. The study was performed in a New Mexican cohort of current and former smokers. Self-reported Hispanic and non-Hispanic white ethnicity was validated by defining genetic ancestry proportions at the individual level using 48 single-nucleotide polymorphism markers. Self-reported ethnicity and genetic ancestry were independently used to assess associations with cross-sectional and longitudinal measures of lung function. Multivariable models were adjusted for indicators of smoking behavior. Self-reported Hispanic ethnicity was significantly associated with lower odds of COPD (odds ratio, 0.49; 95% confidence interval, 0.35-0.71; P = 0.007), and this protection was validated by the observation that Hispanic smokers have reduced risk of rapid decline in lung function (odds ratio, 0.48; 95% confidence interval, 0.30-0.78; P = 0.003). Similar findings were noted when Native American genetic ancestry proportions were used as predictors instead of self-report of Hispanic ethnicity. Hispanic ethnicity is inversely associated with cross-sectional and longitudinal spirometric COPD phenotypes even after adjustment for smoking. Native American genetic ancestry may account for this "Hispanic protection."
    American Journal of Respiratory and Critical Care Medicine 09/2011; 184(11):1254-60. · 11.04 Impact Factor
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    ABSTRACT: To assess whether increased short-acting β(2)-adrenergic agonist (SABA) claims are associated with asthma exacerbations and increased healthcare costs. Cross-sectional study. Patients (N = 93,604) were health plan members aged 6-56 years with at least 2 years of enrollment between July 1, 2003, and June 30, 2007, an asthma diagnosis, and at least 1 asthma medication claim per study year. Two years of administrative claims were collected. SABA use was categorized as 0 (none), (1/2) to 2 (low), 2(1/2) to 6 (moderate), 6(1/2) to 12 (high), and more than 12 (excessive) canister equivalents per year. Multivariate analyses were adjusted for age, sex, geographic region, comorbidities, specialist consultation, controller medication use, and asthma severity. Half of high and excessive SABA users had few or no controller claims. Compared with SABA nonusers, high and excessive SABA users had significantly higher odds (odds ratio [95% confidence interval]) of asthma-related emergency department/urgent care visits (6.47 [5.25, 7.98] and 7.68 [6.04, 9.76], respectively), hospitalizations (5.37 [6.04, 9.76]; 6.90 [4.90, 9.73]), and oral corticosteroid use (2.89 [2.72, 3.08]; 3.71 [3.41, 4.03]). Excessive SABA users had 3.0 times ($1791) and high SABA users had 2.2 times ($1326) higher asthma-related healthcare costs than low SABA users ($595). Total costs also increased with higher SABA use, but with smaller incremental differences between excessive and high SABA users and low SABA users. Increased SABA use is associated with higher total and asthma-related healthcare costs. Opportunity exists to lessen overreliance on SABAs.
    The American journal of managed care 01/2011; 17(1):19-27. · 2.12 Impact Factor
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    ABSTRACT: Chronic bronchitis (CB) is often misdiagnosed or diagnosed at a later stage of chronic obstructive pulmonary disease (COPD). We examined how this later diagnosis may impact health care costs and utilization during the 12 months prior to and 24 months post initial CB diagnosis. This retrospective case-control analysis used claims data from a large US database from July 1, 2003 through June 30, 2007. Patients with CB aged 40 years and older were propensity matched (N = 11,674) to patients without evidence of COPD or asthma by demographics, CB diagnosis quarter/year, and comorbidities. Group differences were assessed using Student's t-test and Pearson chi-square test statistics. Six months prediagnosis, CB patients had higher frequencies of any hospitalization (9.6%, 6.7%; P < 0.05), emergency department/urgent care visits (13.3%, 6.7%; P < 0.05), and prescriptions (97.3%, 94.1%; P < 0.05). Six months postdiagnosis, CB patients had 5.6 times more hospitalizations (P < 0.05) and 3.1 times more emergency department/urgent care visits (P < 0.05) compared with controls. Mean total costs (US$) for CB patients 12 months prediagnosis were significantly higher than controls (months 12-7: $4212, $3826; P < 0.05; months 6-1: $5289, $4285; P < 0.05). CB patients had higher mean total costs ($8919; P < 0.05) 6 months postdiagnosis. Costs remained $2429 higher for CB patients 19-24 months postdiagnosis (P < 0.05). Health care costs and utilization among CB patients are increased both prior to diagnosis and during the 2 years postdiagnosis. This study suggests that not accurately diagnosing CB early has a substantial impact on health care costs, and that the economic burden for CB patients remains elevated even after adjustment for comorbidities associated with COPD.
    International Journal of COPD 01/2011; 6:73-81.
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    American Journal of Respiratory and Critical Care Medicine. 01/2011;
  • Value in Health 01/2011; 14(3). · 2.19 Impact Factor
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    ABSTRACT: This study was conducted to determine COPD severity at the time of diagnosis as confirmed by spirometry in patients treated in a US managed care setting. All patients with one or more inpatient stays, one or more emergency department visits, or two or more outpatient visits with diagnosis codes for COPD during 1994-2006 were identified from the Lovelace Patient Database. From this group, a subset of continuously enrolled patients with evidence in claims of a first available pulmonary function test or pulmonary clinic visit and a confirmatory claim for a COPD diagnosis was selected. Medical chart abstraction was undertaken for this subset to gather information for diagnosis and severity staging of each patient based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD. Of the 12,491 patients with a primary or secondary COPD diagnosis between 1994 and 2006, there were 1520 continuously enrolled patients who comprised the study cohort. Among the 648 eligible records from patients with evidence of a pulmonary function test, 366 were identified by spirometry as having COPD of GOLD stage I or higher (average percentage of predicted forced expiratory volume in 1 second: 60%): 19% were diagnosed at the stage of mild disease (GOLD stage I); 50% at moderate disease (GOLD stage II); and 31% at severe or very severe disease (GOLD stage III or IV, respectively). The majority of patients in these groups were not receiving maintenance treatment. The results demonstrate a very low incidence of early-stage diagnosis, confirmed by a pulmonary function test, of COPD in a large US sample and support calls for increased screening for COPD and treatment upon diagnosis.
    International Journal of COPD 01/2011; 6:573-81.
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    ABSTRACT: Wood smoke-associated chronic obstructive pulmonary disease (COPD) is common in women in developing countries but has not been adequately described in developed countries. 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. 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. 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. 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.
    American Journal of Respiratory and Critical Care Medicine 11/2010; 182(9):1098-104. · 11.04 Impact Factor

Publication Stats

391 Citations
146.22 Total Impact Points


  • 2001–2014
    • Lovelace Respiratory Research Institute
      • • Respiratory Immunology and Asthma Program
      • • Division of Clinical and Outcomes Research
      Albuquerque, New Mexico, United States
  • 2001–2013
    • University of New Mexico
      • • School of Medicine
      • • Department of Family And Community Medicine
      Albuquerque, New Mexico, United States
  • 2012
    • University of Colorado
      • Department of Biostatistics and Informatics
      Denver, CO, United States
  • 2010
    • University of New Mexico Hospitals
      Albuquerque, New Mexico, United States
    • GlaxoSmithKline plc.
      Londinium, England, Belgium