A trans-omics assessment of gene-gene interaction in early-stage NSCLC.

Epigenome-wide gene-gene (G × G) interactions associated with non-small-cell lung cancer (NSCLC) survival may provide insights into molecular mechanisms and therapeutic targets. Hence, we proposed a three-step analytic strategy to identify significant and robust G × G interactions that are relevant to NSCLC survival. In the first step, among 49 billion pairs of DNA methylation probes, we identified 175 775 G × G interactions with PBonferroni ≤ 0.05 in the discovery phase of epigenomic analysis; among them, 15 534 were confirmed with P ≤ 0.05 in the validation phase. In the second step, we further performed a functional validation for these G × G interactions at the gene expression level by way of a two-phase (discovery and validation) transcriptomic analysis, and confirmed 25 significant G × G interactions enriched in the 6p21.33 and 6p22.1 regions. In the third step, we identified two G × G interactions using the trans-omics analysis, which had significant (P ≤ 0.05) epigenetic cis-regulation of transcription and robust G × G interactions at both the epigenetic and transcriptional levels. These interactions were cg14391855 × cg23937960 (ßinteraction  = 0.018, P = 1.87 × 10-12 ), which mapped to RELA × HLA-G (ßinteraction  = 0.218, P = 8.82 × 10-11 ) and cg08872738 × cg27077312 (ßinteraction  = -0.010, P = 1.16 × 10-11 ), which mapped to TUBA1B × TOMM40 (ßinteraction =-0.250, P = 3.83 × 10-10 ). A trans-omics mediation analysis revealed that 20.3% of epigenetic effects on NSCLC survival were significantly (P = 0.034) mediated through transcriptional expression. These statistically significant trans-omics G × G interactions can also discriminate patients with high risk of mortality. In summary, we identified two G × G interactions at both the epigenetic and transcriptional levels, and our findings may provide potential clues for precision treatment of NSCLC.

Health Care Disparities Across the Urban-Rural Divide: A National Study of Individuals with COPD.

PURPOSE: The burden of chronic obstructive pulmonary disease (COPD) is high in rural America. Few studies, however, have examined urban/rural differences in health care access, or racial/ethnic and income disparities stratified by urban/rural residence, among persons with COPD. METHODS: We studied individuals age ≥ 40 years with COPD from the 2018 Behavioral Risk Factor Surveillance System. The primary exposure was "urban" or "rural" county of residence. We examined multiple health and health care access/services outcomes using logistic regressions adjusted for age and sex, and performed analyses stratified by rural/urban county that included additional adjustment for race/ethnicity or income. FINDINGS: Our sample included 34,439 individuals. COPD prevalence was 8.6% in rural counties versus 5.4% in urban counties. Rural residents with COPD were poorer, had less education, worse health, and more disability. Of the rural population with COPD, 12.6% were uninsured, versus 10.4% in urban areas (AOR 1.26; 95% CI: 1.00-1.58). Rural residents with COPD were more likely to have not seen a doctor due to cost (AOR 1.18; 95% CI: 1.02-1.36). Differences in other outcomes were mostly nonsignificant. We observed large access disparities by race/ethnicity and income among individuals in both urban and rural counties, with the highest rates of forgone care among minorities in rural counties. CONCLUSION: Patients with COPD in rural areas experience greater morbidity and obstacles to care than those in urban areas. Racial/ethnic minorities and those with low incomes-particularly in rural areas-are also at greater risk of forgoing doctor visits due to cost. Expanded access to health care could address respiratory health inequities.

Prognostic implications of differences in forced vital capacity in black and white US adults: Findings from NHANES III with long-term mortality follow-up.

BACKGROUND: Because Forced Vital Capacity (FVC) is reduced in Black relative to White Americans of the same age, sex, and height, standard lung function prediction equations assign a lower "normal" range for Black patients. The prognostic implications of this race correction are uncertain. METHODS: We analyzed 5,294 White and 3,743 Black participants age 20-80 in NHANES III, a nationally-representative US survey conducted 1988-94, which we linked to the National Death Index to assess mortality through December 31, 2015. We calculated the FVC-percent predicted among Black and White participants, first applying NHANES III White prediction equations to all persons, and then using standard race-specific prediction equations. We used Cox proportional hazard models to calculate the association between race and all-cause mortality without and with adjustment for FVC (using each FVC metric), smoking, socioeconomic factors, and comorbidities. FINDINGS: Black participants' age- and sex-adjusted mortality was greater than White participants (HR 1.46; 95%CI:1.29, 1.65). With adjustment for FVC in liters (mean 3.7 L for Black participants, 4.3 L for White participants) or FVC percent-predicted using White equations for everyone, Black race was no longer independently predictive of higher mortality (HR∼1.0). When FVC-percent predicted was "corrected" for race, Black individuals again showed increased mortality hazard. Deaths attributed to chronic respiratory disease were infrequent for both Black and White individuals. INTERPRETATION: Lower FVC in Black people is associated with elevated risk of all-cause mortality, challenging the standard assumption about race-based normal limits. Black-White disparities in FVC may reflect deleterious social/environmental exposures, not innate differences. FUNDING: No funding.

Socioeconomic Inequality in Respiratory Health in the US From 1959 to 2018.

Importance: Air quality has improved and smoking rates have declined over the past half-century in the US. It is unknown whether such secular improvements, and other policies, have helped close socioeconomic gaps in respiratory health. Objective: To describe long-term trends in socioeconomic disparities in respiratory disease prevalence, pulmonary symptoms, and pulmonary function. Design, Setting, and Participants: This repeated cross-sectional analysis of the nationally representative National Health and Nutrition Examination Surveys (NHANES) and predecessor surveys, conducted from 1959 to 2018. included 160 495 participants aged 6 to 74 years. Exposures: Family income quintile defined using year-specific thresholds; educational attainment. Main Outcomes and Measures: Trends in socioeconomic disparities in prevalence of current/former smoking among adults aged 25 to 74 years; 3 respiratory symptoms (dyspnea on exertion, cough, and wheezing) among adults aged 40 to 74 years; asthma stratified by age (6-11, 12-17, and 18-74 years); chronic obstructive pulmonary disease ([COPD] adults aged 40-74 years); and 3 measures of pulmonary function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC<0.70) among adults aged 24 to 74 years. Results: Our sample included 160 495 individuals surveyed between 1959 and 2018: 27 948 children aged 6 to 11 years; 26 956 children aged 12 to 17 years; and 105 591 adults aged 18 to 74 years. Income- and education-based disparities in smoking prevalence widened from 1971 to 2018. Socioeconomic disparities in respiratory symptoms persisted or worsened from 1959 to 2018. For instance, from 1971 to 1975, 44.5% of those in the lowest income quintile reported dyspnea on exertion vs 26.4% of those in the highest quintile, whereas from 2017 to 2018 the corresponding proportions were 48.3% and 27.9%. Disparities in cough and wheezing rose over time. Asthma prevalence rose for all children after 1980, but more sharply among poorer children. Income-based disparities in diagnosed COPD also widened over time, from 4.5 percentage points (age- and sex-adjusted) in 1971 to 11.3 percentage points from 2013 to 2018. Socioeconomic disparities in FEV1 and FVC also increased. For instance, from 1971 to 1975, the age- and height-adjusted FEV1 of men in the lowest income quintile was 203.6 mL lower than men in the highest quintile, a difference that widened to 248.5 mL from 2007 to 2012 (95% CI, -328.0 to -169.0). However, disparities in rates of FEV1/FVC lower than 0.70 changed little. Conclusions and Relevance: Socioeconomic disparities in pulmonary health persisted and potentially worsened over the past 6 decades, suggesting that the benefits of improved air quality and smoking reductions have not been equally distributed. Socioeconomic position may function as an independent determinant of pulmonary health.

Risk of Acute Respiratory Distress Syndrome Among Older Adults Living Near Construction and Manufacturing Sites.

BACKGROUND: Construction and manufacturing sites produce airborne toxins that may affect nearby residents' respiratory health. Living in heavy industrial sites has been linked to respiratory conditions such as asthma and pneumonia. However, limited information is available for risk of acute respiratory distress syndrome (ARDS), a form of acute respiratory failure with high incidence among older adults. METHODS: We conducted a nationwide ecologic study to investigate associations between annual ZIP code-level changes in industrial activity and annual changes in ZIP code-level hospital admission rates for older community residents. Using adjusted generalized linear mixed models, we analyzed data from nearly 30 million yearly Medicare beneficiaries for the years 2006 through 2012. RESULTS: We found on average 92,363 hospital admissions for ARDS per year and 646,542 admissions over the course of 7 years. We found that an increase of 10 construction sites per year was associated with a 0.77% (95% confidence interval [CI] = 0.71, 0.84) increase in annual hospital admission rates for ARDS and an increase of 10 manufacturing industries per year was associated with a 1.21% (95% CI = 1.09, 1.33) increase in annual hospital admission rates for ARDS across all ZIP codes. The estimated effect of chemical product manufacturing industry on ARDS was higher than that of total manufacturing industries. Residing in ZIP codes with a high number of construction or manufacturing sites was associated with increased ARDS hospital admissions. CONCLUSIONS: This nationwide ecologic study of older adults suggests that residence in areas with more construction and manufacturing sites is associated with increased ARDS risk.

High-Deductible Health Plans and Healthcare Access, Use, and Financial Strain in Those with Chronic Obstructive Pulmonary Disease.

Rationale: Medical treatment can improve quality of life and avert exacerbations for those with chronic obstructive pulmonary disease (COPD). High-deductible health plans (HDHPs) can increase exposure to medical costs, and might compromise healthcare access and financial well-being for patients with COPD.Objectives: To examine the association of HDHPs with healthcare access, utilization, and financial strain among individuals with COPD.Methods: We analyzed privately insured adults aged 40-64 years with COPD in the 2011-2017 National Health Interview Survey, which uses Internal Revenue Service-specified thresholds to classify health plans as "high" or "traditional" deductible coverage. We assessed the association between enrollment in an HDHP and indicators of cost-related impediments to care, financial strain, and healthcare utilization, adjusting for potential confounders.Results: Our sample included 803 individuals with an HDHP and 1,334 with a traditional plan. The two groups' demographic and health characteristics were similar. Individuals enrolled in an HDHP more frequently reported delayed or foregone care, cost-related medication nonadherence, medical bill problems, and financial strain. They also more frequently reported out-of-pocket healthcare spending in excess of $5,000 a year. Although the two groups' office visit rates were similar, those enrolled in an HDHP were more likely to report a hospitalization or emergency room visit in the past year.Conclusions: For patients with COPD, enrollment in an HDHP was associated with cost-related barriers to care, financial strain, and more frequent emergency room visits and hospitalizations.

Global Health-related Training Opportunities. A National Survey of Pulmonary and Critical Care Medicine Fellowship Programs.

Rationale: Clinical and research training opportunities in global health are of increasing interest to medical trainees, but little is known about such opportunities in U.S.-based pulmonary and pulmonary/critical care medicine (PCCM) fellowship programs.Objectives: Summarize currently available global health-related training opportunities and identify potential barriers to implementing global health curricula among U.S.-based PCCM fellowship programs.Methods: We sent a confidential, online, targeted needs assessment to PCCM fellowship program directors and associate program directors. Data collected included program demographics, currently available global health-related clinical and research training opportunities, potential barriers to the implementation of global health-related programmatic content, and perceived interest in global health-related training opportunities by current and/or prospective trainees. To evaluate for nonresponse bias, we performed an online search to identify global health-related training opportunities offered by nonresponding programs.Results: Out of 171 surveyed programs, 63 PCCM fellowship programs (37%) provided survey responses. Most responses (n = 56, 89%) were from combined PCCM training programs; 66% (n = 40) of programs offered at least one component of global health-related clinical or research training. Overall, 27% (n = 17) had a Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant (National Institutes of Health T32), 73% (n = 46) had fewer than 35 faculty members, and 51% (n = 32) had at least one faculty member conducting global health-focused research. Most responding programs (66%, n = 40) offered at least one global health-related educational component. Among programs that would like to offer global health-related training components, the most common barriers included competing priorities for lecture content and a lack of in-division mentors with global health experience, a champion for global health-related activities, and established partnerships outside the United States.Conclusions: PCCM program leaders are interested in offering global health-related training opportunities, but important barriers include lack of mentorship, dedicated fellowship time, and established global partnerships. Future research is needed to better understand global health-related interests and training needs of incoming fellows and to design creative solutions for providing global health-related training across academic institutions with variable global health-related training capacities.

Are per capita carbon emissions predictable across countries?

BACKGROUND: China and other developing countries in Asia follow similar economic growth patterns described by the flying geese (FG) model, which explains the "catching-up" process of industrialization in latecomer economies. Japan, newly industrialized economies, and China have followed this path, with similar economic development trajectories. Based on the FG model, we postulated a "flying S" hypothesis stating that if a country is located within an FG region and its energy matrix is relatively constant, its per capita CO2 emission curve will mirror that of "leading geese" countries in the same FG group. METHOD: Historical CO2 emissions data were obtained from literature review and national reports and were calculated using bottom-up methods. A sigmoid-shaped, non-linear mixed effect model was applied to examine ex post data with 1000 simulated predictions to construct 95% empirical bands from these fits. By multiplying by estimated population, we predicted total emissions of selected FG countries. RESULTS: Per capita CO2 emissions from the same FG group mirror each other, especially among second and third industrial sectors. We estimated an annual 18,252.24 million tons of CO2 emissions (MtCO2) (95% CI = 9458.88-23,972.88) in China and 8281.76 MtCO2 (95% CI = 2765.68-14,959.12) in India in 2030. CONCLUSION: This study bridges the macroeconomic FG paradigm to study climate change and proposes a "flying S" hypothesis to predict greenhouse gas emissions in East Asia. By applying our theory to empirical data, we provide an alternative framework to predict CO2 emissions in 2030 and beyond.

Impact of Long-Term Exposures to Ambient PM2.5 and Ozone on ARDS Risk for Older Adults in the United States.

BACKGROUND: Chronic exposures to particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5) and ozone pollution can affect respiratory function. ARDS, an often lethal respiratory failure, is most common among older adults. However, few epidemiology studies have investigated an association between air pollution and the risk of ARDS. METHODS: This observational study was conducted to estimate air pollution exposures at the ZIP code level and hospital admissions with ARDS among US Medicare beneficiaries aged ≥ 65 years from 2000 to 2012. A two-pollutant generalized linear mixed model, adjusting for sex, age, race, median household income, smoking, and weather, was applied. RESULTS: There were a total of 1,164,784 hospital admissions with ARDS in the cohort. Increases of 1 µg/m3 in annual average PM2.5 and of 1 parts per billion in annual average ozone were associated with increases in annual hospital admission rates for ARDS of 0.72% (95% CI, 0.62-0.82) and 0.15% (95% CI, 0.08-0.22), respectively. In low-pollution regions (annual average PM2.5 level < 12 µg/m3 and annual average ozone level < 45 parts per billion), the same annual increase in PM2.5 and ozone were associated with increases in annual hospital admission rates for ARDS of 1.50% (95% CI, 1.27-1.72) and 0.27% (95% CI, 0.16-0.38). CONCLUSIONS: Long-term exposures to PM2.5 and ozone were associated with increased risk of ARDS among older adults in the United States, including exposures below current annual US National Ambient Air Quality Standards.

Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks.

Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. To the best of our knowledge, this is the first study systematically integrating in vivo, transcriptomics, metabolomics, and lipidomics to assess PEPs inhalation exposure-induced disease risks using a rat model.

A Prospective Cohort Study Examining the Associations of Maternal Arsenic Exposure With Fetal Loss and Neonatal Mortality.

Arsenic crosses the placenta, possibly increasing the risk of adverse reproductive outcomes. We aimed to examine the association between maternal arsenic exposure and fetal/neonatal survival using data from a prospective cohort study of 1,616 maternal-infant pairs recruited at a gestational age of ≤16 weeks in Bangladesh (2008-2011). Arsenic concentration in maternal drinking water was measured at enrollment. Extended Cox regression (both time-dependent coefficients and step functions) was used to estimate the time-varying association between maternal arsenic exposure and fetal/neonatal death (all mortality between enrollment and 1 month after birth). In a sensitivity analysis, we assessed gestational arsenic exposure using maternal urine samples taken at enrollment. We observed 203 fetal losses and 20 neonatal deaths. Higher arsenic exposure was associated with a slightly decreased mortality rate up to the middle of the second trimester, and then the mortality rate switched directions around 20 weeks' gestation. In the step function model, the hazard ratios for combined mortality (fetal loss and neonatal death) per unit increase in the natural log of drinking water arsenic concentration (µg/L) ranged from 1.35 (95% CI: 1.08, 1.69) in weeks 25-28 to 0.81 (95% CI: 0.65, 1.02) in weeks 9-12. This nonlinear association suggests that arsenic may exert survival pressure on developing fetuses, potentially contributing to survival bias, and may also indicate that arsenic toxicity differs by fetal developmental stage.

Validation of a Dish-Based Semiquantitative Food Questionnaire in Rural Bangladesh.

A locally validated tool was needed to evaluate long-term dietary intake in rural Bangladesh. We assessed the validity of a 42-item dish-based semi-quantitative food frequency questionnaire (FFQ) using two 3-day food diaries (FDs). We selected a random subset of 47 families (190 participants) from a longitudinal arsenic biomonitoring study in Bangladesh to administer the FFQ. Two 3-day FDs were completed by the female head of the households and we used an adult male equivalent method to estimate the FD for the other participants. Food and nutrient intakes measured by FFQ and FD were compared using Pearson's and Spearman's correlation, paired t-test, percent difference, cross-classification, weighted Kappa, and Bland-Altman analysis. Results showed good validity for total energy intake (paired t-test, p < 0.05; percent difference <10%), with no presence of proportional bias (Bland-Altman correlation, p > 0.05). After energy-adjustment and de-attenuation for within-person variation, macronutrient intakes had excellent correlations ranging from 0.55 to 0.70. Validity for micronutrients was mixed. High intraclass correlation coefficients (ICCs) were found for most nutrients between the two seasons, except vitamin A. This dish-based FFQ provided adequate validity to assess and rank long-term dietary intake in rural Bangladesh for most food groups and nutrients, and should be useful for studying dietary-disease relationships.

Exposure Enriched Case-Control (EECC) Design for the Assessment of Gene-Environment Interaction.

Genetic susceptibility and environmental exposure both play an important role in the aetiology of many diseases. Case-control studies are often the first choice to explore the joint influence of genetic and environmental factors on the risk of developing a rare disease. In practice, however, such studies may have limited power, especially when susceptibility genes are rare and exposure distributions are highly skewed. We propose a variant of the classical case-control study, the exposure enriched case-control (EECC) design, where not only cases, but also high (or low) exposed individuals are oversampled, depending on the skewness of the exposure distribution. Of course, a traditional logistic regression model is no longer valid and results in biased parameter estimation. We show that addition of a simple covariate to the regression model removes this bias and yields reliable estimates of main and interaction effects of interest. We also discuss optimal design, showing that judicious oversampling of high/low exposed individuals can boost study power considerably. We illustrate our results using data from a study involving arsenic exposure and detoxification genes in Bangladesh.

Increased Risk of Respiratory Mortality Associated with the High-Tech Manufacturing Industry: A 26-Year Study.

Global high-tech manufacturers are mainly located in newly industrialized countries, raising concerns about adverse health consequences from industrial pollution for people living nearby. We investigated the ecological association between respiratory mortality and the development of Taiwan's high-tech manufacturing, taking into account industrialization and socioeconomic development, for 19 cities and counties-6 in the science park group and 13 in the control group-from 1982 to 2007. We applied a linear mixed-effects model to analyze how science park development over time is associated with age-adjusted and sex-specific mortality rates for asthma and chronic obstructive pulmonary disease (COPD). Asthma and female COPD mortality rates decreased in both groups, but they decreased 9%-16% slower in the science park group. Male COPD mortality rates increased in both groups, but the rate increased 10% faster in the science park group. Science park development over time was a significant predictor of death from asthma (p ≤ 0.0001) and COPD (p = 0.0212). The long-term development of clustered high-tech manufacturing may negatively affect nearby populations, constraining health advantages that were anticipated, given overall progress in living standards, knowledge, and health services. National governments should incorporate the long-term health effects on local populations into environmental impact assessments.

Global Health Education in Pulmonary and Critical Care Medicine Fellowships.

A growing number of pulmonary and critical care medicine fellowship programs in the United States offer global health training opportunities. Formal, integrated global health programs within pulmonary and critical care fellowships are relatively new but are built on principles and ideals of global health that focus on the mutually beneficial exchange of knowledge and social justice. Although core competencies consistent with these overarching themes in global health education have not been formalized for pulmonary and critical care trainees, relevant competency areas include clinical knowledge, international research training, cultural competency, and clinical and research capacity building. Existing global health education in U.S. pulmonary and critical care medicine training programs can generally be classified as one of three different models: integrated global health tracks, global health electives, and additional research years. Successful global health education programs foster partnerships and collaborations with international sites that emphasize bidirectional exchange. This bidirectional exchange includes ongoing, equitable commitments to mutual opportunities for training and professional development, including a focus on the particular knowledge and skill sets critical for addressing the unique priorities of individual countries. However, barriers related to the availability of mentorship, funding, and dedicated time exist to expanding global health education in pulmonary and critical care medicine. The implementation of global health training within pulmonary and critical care medicine programs requires continued optimization, but this training is essential to prepare the next generation of physicians to address the global aspects of respiratory disease and critical illness.

Socioeconomic status is associated with reduced lung function in China: an analysis from a large cross-sectional study in Shanghai.

BACKGROUND: An inverse association between socioeconomic status and pulmonary function has emerged in many studies. However, the mediating factors in this relationship are poorly understood, and might be expected to differ between countries. We sought to investigate the relationship between socioeconomic status and lung function in China, a rapidly industrializing nation with unique environmental challenges, and to identify potentially-modifiable environmental mediators. METHODS: We used data from the Shanghai Putuo Study, a cross-sectional study performed in Shanghai, China. Participants completed a questionnaire and spirometry. The primary exposure was socioeconomic status, determined by education level. The primary outcomes were FEV1 and FVC percent predicted. Multiple linear regressions were used to test this association, and the percent explained by behavioral, environmental, occupational, and dietary variables was determined by adding these variables to a base model. RESULTS: The study population consisted of a total of 22,878 study subjects that were 53.3 % female and had a mean age of 48. In the final multivariate analysis, the effect estimates for FEV1 and FVC percent predicted for low socioeconomic status (compared to high) were statistically significant at a p-value of <0.01. Smoking, biomass exposure, mode of transportation to work, a diet low in fruits or vegetables, and occupational category partially attenuated the relationship between SES and lung function. In a fully-adjusted age-stratified analysis, the socioeconomic disparity in lung function widened with increasing age. CONCLUSIONS: We found cross-sectional evidence of socioeconomic disparities in pulmonary function in Shanghai. These differences increased with age and were partially explained by potentially modifiable exposures.

Women and lung cancer: what is new?

In the last 20 years, there has been an increased focus on gender differences in health and disease. The earliest studies of lung cancer enrolled mainly men, as the incidence of lung cancer among women was exceedingly low. As social patterns changed around World War II and women began to smoke more, the epidemiology of lung cancer has changed. The higher percentage of lung cancer in nonsmoking women as compared with nonsmoking men suggests that lung cancer behaves differently in women. Studies of lung cancer in women indicate that there are differences in risk factors, histology, pathophysiology, treatment outcomes, and prognosis as compared with men. The purpose of this review is to provide a concise summary of the literature on lung cancer as it pertains to women, with an emphasis on new areas of research and treatment options.

Genetic variants on 15q25.1, smoking, and lung cancer: an assessment of mediation and interaction.

Genome-wide association studies have identified variants on chromosome 15q25.1 that increase the risks of both lung cancer and nicotine dependence and associated smoking behavior. However, there remains debate as to whether the association with lung cancer is direct or is mediated by pathways related to smoking behavior. Here, the authors apply a novel method for mediation analysis, allowing for gene-environment interaction, to a lung cancer case-control study (1992-2004) conducted at Massachusetts General Hospital using 2 single nucleotide polymorphisms, rs8034191 and rs1051730, on 15q25.1. The results are validated using data from 3 other lung cancer studies. Tests for additive interaction (P = 2 × 10(-10) and P = 1 × 10(-9)) and multiplicative interaction (P = 0.01 and P = 0.01) were significant. Pooled analyses yielded a direct-effect odds ratio of 1.26 (95% confidence interval (CI): 1.19, 1.33; P = 2 × 10(-15)) for rs8034191 and an indirect-effect odds ratio of 1.01 (95% CI: 1.00, 1.01; P = 0.09); the proportion of increased risk mediated by smoking was 3.2%. For rs1051730, direct- and indirect-effect odds ratios were 1.26 (95% CI: 1.19, 1.33; P = 1 × 10(-15)) and 1.00 (95% CI: 0.99, 1.01; P = 0.22), respectively, with a proportion mediated of 2.3%. Adjustment for measurement error in smoking behavior allowing up to 75% measurement error increased the proportions mediated to 12.5% and 9.2%, respectively. These analyses indicate that the association of the variants with lung cancer operates primarily through other pathways.

Assessment of occupational exposure to manganese and other metals in welding fumes by portable X-ray fluorescence spectrometer.

Elemental analysis of welding fume samples can be done using several laboratory-based techniques. However, portable measurement techniques could offer several advantages. In this study, we sought to determine whether the portable X-ray fluorescence spectrometer (XRF) is suitable for analysis of five metals (manganese, iron, zinc, copper, and chromium) on 37-mm polytetrafluoroethylene filters. Using this filter fitted on a cyclone in line with a personal pump, gravimetric samples were collected from a group of boilermakers exposed to welding fumes. We assessed the assumption of uniform deposition of these metals on the filters, and the relationships between measurement results of each metal obtained from traditional laboratory-based XRF and the portable XRF. For all five metals of interest, repeated measurements with the portable XRF at the same filter area showed good consistency (reliability ratios are equal or close to 1.0 for almost all metals). The portable XRF readings taken from three different areas of each filter were not significantly different (p-values = 0.77 to 0.98). This suggested that the metal rich PM(2.5) deposits uniformly on the samples collected using this gravimetric method. For comparison of the two XRFs, the results from the portable XRF were well correlated and highly predictive of those from the laboratory XRF. The Spearman correlation coefficients were from 0.325 for chromium, to 0.995 for manganese and 0.998 for iron. The mean differences as a percent of the mean laboratory XRF readings were also small (<5%) for manganese, iron, and copper. The differences were greater for zinc and chromium, which were present at very low amounts in our samples and below the limits of detection of the portable XRF for many of the samples. These five metals were moderately to strongly correlated with the total fine particle fraction on filters (Spearman rho = 0.41 for zinc to 0.97 for iron). Such strong correlations and comparable results suggested that the portable XRF could be used as an effective and reliable tool for exposure assessment in many studies.

Second-hand smoke and chronic bronchitis in Taiwanese women: a health-care based study.

BACKGROUND: Cigarette smoking cannot fully explain the epidemiologic characteristics of chronic obstructive pulmonary disease (COPD) in women, particularly for those who rarely smoke, but COPD risk is not less than men. The aim of our study is to investigate the relationship between second-hand smoke (SHS) exposure and chronic bronchitis in Taiwanese women. METHODS: We used Taiwan's National Health Insurance Bureau claims data in 1999, and cross-checked using criteria set by the American Thoracic Society; there were 33 women with chronic bronchitis, 182 with probable chronic bronchitis, and 205 with no chronic bronchitis during our interview time between 2000 and 2005. We measured second-hand smoke (SHS) exposure by self-reported measures (household users and duration of exposure), and validated this by measuring urinary cotinine levels of a subset subjects. Classification of chronic bronchitis was also based on spirometry defined according to the GOLD guidelines to get the severity of COPD. RESULTS: Women who smoked and women who had been exposed to a lifetime of SHS were 24.81-fold (95% CI: 5.78-106.38) and 3.65-fold (95% CI: 1.19-11.26) more likely to have chronic bronchitis, respectively, than those who had not been exposed to SHS. In addition, there was a significant increasing trend between the severity of COPD and exposure years of SHS (p < 0.01). The population attributable risk percentages of chronic bronchitis for smokers and those exposed to SHS were 23.2 and 47.3% respectively. CONCLUSIONS: These findings indicate that, besides cigarette smoking, exposure to SHS is a major risk factor for chronic bronchitis in Taiwanese women.