Editorials; smoking; pharmacology; cessation
Air pollution in many Chinese cities has been so severe in recent years that a special terminology, the “Chinese haze”, was created to describe China’s air quality problem. Historically, the problem of Chinese haze has developed several decades after Western high-income countries have significantly improved their air quality from the smog-laden days in the early- and mid-20th century. Hence it is important to provide a global and historical perspective to help China combat the current air pollution problems. In this regard, this article addresses the followings specific questions: (I) What is the Chinese haze in comparison with the sulfurous (London-type) smog and the photochemical (Los Angeles-type) smog? (II) How does Chinese haze fit into the current trend of global air pollution transition? (III) What are the major mitigation measures that have improved air quality in Western countries? and (IV) What specific recommendations for China can be derived from lessons and experiences from Western countries?
Air pollution; emissions; health effects; clean air legislation
Background: Particulate matter (PM) in outdoor air pollution was recently designated a Group I carcinogen by the International Agency for Research on Cancer (IARC). This determination was based on the evidence regarding the relationship of PM2.5 and PM10 to lung cancer risk; however, the IARC evaluation did not include a quantitative summary of the evidence.
Objective: Our goal was to provide a systematic review and quantitative summary of the evidence regarding the relationship between PM and lung cancer.
Methods: We conducted meta-analyses of studies examining the relationship of exposure to PM2.5 and PM10 with lung cancer incidence and mortality. In total, 18 studies met our inclusion criteria and provided the information necessary to estimate the change in lung cancer risk per 10-μg/m3 increase in exposure to PM. We used random-effects analyses to allow between-study variability to contribute to meta-estimates.
Results: The meta-relative risk for lung cancer associated with PM2.5 was 1.09 (95% CI: 1.04, 1.14). The meta-relative risk of lung cancer associated with PM10 was similar, but less precise: 1.08 (95% CI: 1.00, 1.17). Estimates were robust to restriction to studies that considered potential confounders, as well as subanalyses by exposure assessment method. Analyses by smoking status showed that lung cancer risk associated with PM2.5 was greatest for former smokers [1.44 (95% CI: 1.04, 2.01)], followed by never-smokers [1.18 (95% CI: 1.00, 1.39)], and then current smokers [1.06 (95% CI: 0.97, 1.15)]. In addition, meta-estimates for adenocarcinoma associated with PM2.5 and PM10 were 1.40 (95% CI: 1.07, 1.83) and 1.29 (95% CI: 1.02, 1.63), respectively.
Conclusion: The results of these analyses, and the decision of the IARC Working Group to classify PM and outdoor air pollution as carcinogenic (Group 1), further justify efforts to reduce exposures to air pollutants that can arise from many sources.
Citation: Hamra GB, Guha N, Cohen A, Laden F, Raaschou-Nielsen O, Samet JM, Vineis P, Forastiere F, Saldiva P, Yorifuji T, Loomis D. 2014. Outdoor particulate matter exposure and lung cancer: a systematic review and meta-analysis. Environ Health Perspect 122:906–911; http://dx.doi.org/10.1289/ehp.1408092
Background: Nitrogen dioxide (NO2), a ubiquitous atmospheric pollutant, may enhance the asthmatic response to allergens through eosinophilic activation in the airways. However, the effect of NO2 on inflammation without allergen exposure is poorly studied.
Objectives: We investigated whether repeated peaks of NO2, at various realistic concentrations, induce changes in airway inflammation in asthmatics.
Methods: Nineteen nonsmokers with asthma were exposed at rest in a double-blind, crossover study, in randomized order, to 200 ppb NO2, 600 ppb NO2, or clean air once for 30 min on day 1 and twice for 30 min on day 2. The three series of exposures were separated by 2 weeks. The inflammatory response in sputum was measured 6 hr (day 1), 32 hr (day 2), and 48 hr (day 3) after the first exposure, and compared with baseline values measured twice 10–30 days before the first exposure.
Results: Compared with baseline measurements, the percentage of eosinophils in sputum increased by 57% after exposure to 600 ppb NO2 (p = 0.003) but did not change significantly after exposure to 200 ppb. The slope of the association between the percentage of eosinophils and NO2 exposure level was significant (p = 0.04). Eosinophil cationic protein in sputum was highly correlated with eosinophil count and increased significantly after exposure to 600 ppb NO2 (p = 0.001). Lung function, which was assessed daily, was not affected by NO2 exposure.
Conclusions: We observed that repeated peak exposures of NO2 performed without allergen exposure were associated with airway eosinophilic inflammation in asthmatics in a dose-related manner.
Citation: Ezratty V, Guillossou G, Neukirch C, Dehoux M, Koscielny S, Bonay M, Cabanes PA, Samet JM, Mure P, Ropert L, Tokarek S, Lambrozo J, Aubier M. 2014. Repeated nitrogen dioxide exposures and eosinophilic airway inflammation in asthmatics: a randomized crossover study. Environ Health Perspect 122:850–855; http://dx.doi.org/10.1289/ehp.1307240
While hair samples are easier to collect and less expensive to store and transport than biological fluids, and hair nicotine characterizes tobacco exposure over a longer time period than blood or urine cotinine, information on its utility, compared with salivary cotinine, is still limited. We conducted a cross-sectional study with 289 participants (107 active smokers, 105 passive smokers with self-reported secondhand smoke (SHS) exposure, and 77 non-smokers with no SHS exposure) in Baltimore (Maryland, USA). A subset of the study participants (n = 52) were followed longitudinally over a two-month interval. Median baseline hair nicotine concentrations for active, passive and non-smokers were 16.2, 0.36, and 0.23 ng/mg, respectively, while those for salivary cotinine were 181.0, 0.27, and 0.27 ng/mL, respectively. Hair nicotine concentrations for 10% of passive or non-smokers were higher than the 25th percentile value for active smokers while all corresponding salivary cotinine concentrations for them were lower than the value for active smokers. This study showed that hair nicotine concentration values could be used to distinguish active or heavy passive adult smokers from non-SHS exposed non-smokers. Our results indicate that hair nicotine is a useful biomarker for the assessment of long-term exposure to tobacco smoke.
biomarker; hair nicotine; salivary cotinine; cutoff value
Causal inference has a central role in public health; the determination that an association is causal indicates the possibility for intervention. We review and comment on the long-used guidelines for interpreting evidence as supporting a causal association and contrast them with the potential outcomes framework that encourages thinking in terms of causes that are interventions. We argue that in public health this framework is more suitable, providing an estimate of an action’s consequences rather than the less precise notion of a risk factor’s causal effect. A variety of modern statistical methods adopt this approach. When an intervention cannot be specified, causal relations can still exist, but how to intervene to change the outcome will be unclear. In application, the often-complex structure of causal processes needs to be acknowledged and appropriate data collected to study them. These newer approaches need to be brought to bear on the increasingly complex public health challenges of our globalized world.
causation; causal modeling; causal framework; epidemiology
Although diabetes increases the risk of cardiovascular disease (CVD) and mortality, the dose-response relationship between fasting glucose levels below those diagnostic of diabetes with cardiovascular events has not been well characterized.
RESEARCH DESIGN AND METHODS
A prospective cohort study of more than one million Koreans was conducted with a mean follow-up of 16 years. A total of 1,197,384 Korean adults with no specific medical conditions diagnosed were classified by baseline fasting serum glucose level. Associations of fasting glucose level with CVD incidence and mortality, stroke incidence and mortality, and all-cause mortality were analyzed using multivariate proportional hazards regression.
The relationships between fasting glucose levels and CVD risks generally followed J-shape curves, with lowest risk in the glucose range of 85–99 mg/dL. As fasting glucose levels increased to >100 mg/dL, risks for CVD, ischemic heart disease, myocardial infarction, and thrombotic stroke progressively increased, but risk for hemorrhagic stroke did not. Fasting glucose levels <70 mg/dL were associated with increased risk of all stroke (hazard ratio 1.06, 95% CI 1.01–1.11) in men and (hazard ratio 1.11, 1.05–1.17) in women.
Both low glucose level and impaired fasting glucose should be considered as predictors of risk for stroke and coronary heart disease. The fasting glucose level associated with the lowest cardiovascular risk may be in a narrow range.
Cigarette flavorings, with the exception of menthol, have been banned in the United States under the Family Smoking Prevention and Tobacco Control Act. Given the large number of menthol cigarette smokers in the United States, we investigated whether cigarette type (nonmenthol or menthol) is associated with peripheral artery disease (PAD).
The authors studied 5,973 adults, 40 years of age and older, who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Smoking status and cigarette type were derived from self-reported questionnaires. PAD was defined as an ankle-brachial blood pressure index <0.9 in at least 1 leg.
Fifty percent of participants were never-smokers compared to 31%, 14%, and 5% of former, current nonmenthol, and current menthol cigarette smokers, respectively. The weighted prevalence of PAD in the study population was 5%. After multivariable adjustment, the odds ratios for PAD were 1.44 (95% CI: 0.97, 2.15), 3.65 (95% CI: 1.57, 8.50), and 2.51 (95% CI: 1.09, 5.80) comparing former, current nonmenthol cigarette smokers, and current menthol cigarette smokers to never-smokers. The associations between smoking and PAD were similar for smokers of nonmenthol and menthol cigarettes (p value for heterogeneity = .59).
In a representative sample of the U.S. population, current use of both menthol and nonmenthol cigarettes was associated with increased prevalence of PAD, with no difference in risk between cigarette types.
Recent air pollutant measurement data document unique aspects of the air pollution mixture near roadways, and an expanding body of epidemiological data suggests increased risks for exacerbation of asthma and other respiratory diseases, premature mortality, and certain cancers and birth outcomes from air pollution exposures in populations residing in relatively close proximity to roadways. The Workshop on Traffic, Health, and Infrastructure Planning, held in February 2004, was convened to provide a forum for interdisciplinary discussion of motor vehicle emissions, exposures and potential health effects related to proximity to motor vehicle traffic. This report summarizes the workshop discussions and findings regarding the current science on this issue, identifies planning and policy issues related to localized motor vehicle emissions and health concerns, and provides recommendations for future research and policy directions.
air pollution; exposure assessment; health effects; motor vehicle emissions; traffic proximity
The “Air Pollution and Health: A Combined European and North American Approach” (APHENA) project is a collaborative analysis of multi-city time-series data on the association between air pollution and adverse health outcomes. The main objective of APHENA was to examine the coherence of findings of time-series studies relating short-term fluctuations in air pollution levels to mortality and morbidity in 125 cities in Europe, the US, and Canada. Multi-city time-series analysis was conducted using a two-stage approach. We used Poisson regression models controlling for overdispersion with either penalized or natural splines to adjust for seasonality. Hierarchical models were used to obtain an overall estimate of excess mortality associated with ozone and to assess potential effect modification. Potential effect modifiers were city-level characteristics related to exposure to other ambient air pollutants, weather, socioeconomic status, and the vulnerability of the population. Regionally pooled risk estimates from Europe and the US were similar; those from Canada were substantially higher. The pooled estimated excess relative risk associated with a 10 µg/m3 increase in 1 h daily maximum O3 was 0.26 % (95 % CI, 0.15 %, 0.37 %). Across regions, there was little consistent indication of effect modification by age or other effect modifiers considered in the analysis. The findings from APHENA on the effects of O3 on mortality in the general population were comparable with previously reported results and relatively robust to the method of data analysis. Overall, there was no indication of strong effect modification by age or ecologic variables considered in the analysis.
Ozone; Mortality; Time-series; Multi-city; Cardiovascular; Respiratory
Although the prevalence of tobacco use is decreasing in many high-income countries, it is increasing in many low-and middle-income countries. The health and economic burden of increasing tobacco use and dependence is predictable and will have devastating effects in countries with limited resources, particularly for vulnerable populations such as pregnant women. We sought to review effective tobacco prevention and intervention strategies for decreasing tobacco use and secondhand smoke exposure before and during pregnancy in high-, middle-, and low-income countries. We reviewed several types of interventions, including population-level efforts (increasing tobacco prices, implementing tobacco control policies), community interventions, clinical interventions, and pharmacological treatments.
A second purpose of this report is to present findings of an international expert working group that was convened to review the evidence and to establish research priorities in the following areas: 1) preventing the uptake and reducing tobacco use among girls and women of reproductive age and 2) reducing tobacco use and secondhand smoke exposure among pregnant women. The working group considered the evidence on existing interventions in terms of burden of disease, intervention impact, intervention costs, feasibility of integration into existing services, uniqueness of the contribution, and overall feasibility. Finally, we present the working group’s recommendations for intervention research priorities.
Global; tobacco; perinatal and reproductive health
In the US, cigarette flavorings are banned, with the exception of menthol. The cooling effects of menthol could facilitate the absorption of tobacco toxicants. We examined levels of biomarkers of tobacco exposure among US smokers of menthol and non-menthol cigarettes.
We studied 4,603 White, African-American, and Mexican-American current smokers ≥ 20 years of age who participated in the National Health and Nutrition Examination Survey from 1999 through 2010 and had data on cigarette type and serum cotinine, blood cadmium, and blood lead concentrations. Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL) was studied in 1,607 participants with available measures.
A total of 3,210 (74.3%) participants smoked non-menthol cigarettes compared to 1,393 (25.7%) participants who smoked menthol cigarettes. The geometric mean concentrations comparing smokers of non-menthol to menthol cigarettes were 163.1 vs. 175.9 ng/mL for serum cotinine; 0.95 vs. 1.02 μg/L for blood cadmium; 1.87 vs. 1.75 μg/dL for blood lead; and 0.27 vs. 0.23 ng/mL for urine NNAL. After multivariable adjustment, the ratios (95% confidence interval [CI]) comparing smokers of menthol to non-menthol cigarettes were 1.03 (0.95, 1.11) for cotinine, 1.10 (1.04, 1.16) for cadmium, 0.95 (0.90, 1.01) for lead, and 0.81 (0.65, 1.01) for NNAL.
In a representative sample of US adult smokers, current menthol cigarette use was associated with increased concentration of blood cadmium, an established carcinogen and highly toxic metal, but not with other biomarkers.
These findings provide information regarding possible differences in exposure to toxic constituents among menthol cigarette smokers compared to non-menthol cigarette smokers.
cigarette smoking; menthol; biomarkers
Physicians have a key role to play in combating tobacco use and reducing the tobacco induced harm to health. However, there is a paucity of information about tobacco-use and cessation among physicians in developing countries. To assess the need for and nature of smoking cessation services among physicians in developing countries, a detailed literature review of studies published in English, between 1987 and 2010 was carried out. The electronic databases Medline and Pub Med were searched for published studies. The findings show that there are regional variations in the current smoking prevalence, quitting intentions, and cessation services among physicians. Smoking prevalence (median) was highest in Central/Eastern Europe (37%), followed by Africa (29%), Central and South America (25%) and Asia (17.5%). There were significant gender differences in smoking prevalence across studies, with higher prevalence among males than females. Smoking at work or in front of patients was commonly practiced by physicians in some countries. Asking about smoking status or advising patients to quit smoking was not common practice among the physicians, especially among smoker physicians. Organized smoking cessation programs for physicians did not exist in all of these regions. This review suggests that while smoking of physicians varies across different developing regions; prevalence rates tend to be higher than among physicians in developed countries. Quitting rates were low among the physicians, and the delivery of advice on quitting smoking was not common across the studies. To promote tobacco control and increase cessation in populations, there is a need to build physicians’ capacity so that they can engage in tobacco use prevention and cessation activities.
tobacco use; physicians; developing countries; smoking cessation; review literature
Restrictions on smoking in public places have become increasingly widespread in the United States, particularly since the year 2005. National-scale studies in Europe and local-scale studies in the United States have found decreases in hospital admissions for acute myocardial infarction (AMI) following smoking bans. The authors analyzed AMI admission rates for the years 1999–2008 in 387 US counties that enacted comprehensive smoking bans across 9 US states, using a study population of approximately 6 million Medicare enrollees aged 65 years or older. Effects of smoking bans on AMI admissions were estimated by using Poisson regression with linear and nonlinear adjustment for secular trend and random effects at the county level. Under the assumption of linearity in the secular trend of declining AMI, smoking bans were associated with a statistically significant ban-associated decrease in admissions for AMI in the 12 months following the ban. However, the estimated effect was attenuated to nearly zero when the assumption of linearity in the underlying trend was relaxed. This analysis demonstrates that estimation of potential health benefits associated with comprehensive smoking bans is challenged by the need to adjust for nonlinearity in secular trend.
environmental tobacco smoke; mixed-effects models; secondhand smoke; smoking bans
In the absence of comprehensive smoking bans in public places, bars and nightclubs have the highest concentrations of secondhand tobacco smoke, posing a serious health risk for workers in these venues.
To assess exposure of bar and nightclub employees to secondhand smoke, including non-smoking and smoking employees.
Between 2007 and 2009, we recruited approximately 10 venues per city and up to 5 employees per venue in 24 cities in the Americas, Eastern Europe, Asia and Africa. Air nicotine concentrations were measured for 7 days in 238 venues. To evaluate personal exposure to secondhand smoke, hair nicotine concentrations were also measured for 625 non-smoking and 311 smoking employees (N=936).
Median (interquartile range [IQR]) air nicotine concentrations were 3.5 (1.5, 8.5) µg/m3 and 0.2 (0.1, 0.7) µg/m3 in smoking and smoke-free venues, respectively. Median (IQR) hair nicotine concentrations were 6.0 (1.6, 16.0) ng/mg and 1.7 (0.5, 5.5) ng/mg in smoking and non-smoking employees, respectively. After adjustment for age, sex, education, living with a smoker, hair treatment and region, a 2-fold increase in air nicotine concentrations was associated with a 30% (95% confidence interval 23%, 38%) increase in hair nicotine concentrations in non-smoking employees and with a 10% (2%, 19%) increase in smoking employees.
Occupational exposure to secondhand smoke, assessed by air nicotine, resulted in elevated concentrations of hair nicotine among non-smoking and smoking bar and nightclub employees. The high levels of airborne nicotine found in bars and nightclubs and the contribution of this exposure to employee hair nicotine concentrations support the need for legislation measures that ensure complete protection from secondhand smoke in these venues.
nicotine; tobacco smoke pollution; workplace
The causative association between tobacco use and lung cancer is a well-established fact. However, lung cancer also occurs, at surprisingly high rates, in lifelong never smokers. In fact, lung cancer in never smokers is among the leading causes of cancer-related mortality. This CCR Focus summarizes recent data, identifies knowledge deficits, and suggests future research directions with regard to this critically important subset of lung cancer patients.
Although many time-series studies of ozone and mortality have identified positive associations, others have yielded null or inconclusive results, making the results of these studies difficult to interpret.
We performed a meta-analysis of 144 effect estimates from 39 time-series studies, and estimated pooled effects by lags, age groups, cause-specific mortality, and concentration metrics. We compared results with pooled estimates from the National Morbidity, Mortality, and Air Pollution Study (NMMAPS), a time-series study of 95 large U.S. urban centers from 1987 to 2000.
Both meta-analysis and NMMAPS results provided strong evidence of a short-term association between ozone and mortality, with larger effects for cardiovascular and respiratory mortality, the elderly, and current-day ozone exposure. In both analyses, results were insensitive to adjustment for particulate matter and model specifications. In the meta-analysis, a 10-ppb increase in daily ozone at single-day or 2-day average of lags 0, 1, or 2 days was associated with an 0.87% increase in total mortality (95% posterior interval = 0.55% to 1.18%), whereas the lag 0 NMMAPS estimate is 0.25% (0.12% to 0.39%). Several findings indicate possible publication bias: meta-analysis results were consistently larger than those from NMMAPS; meta-analysis pooled estimates at lags 0 or 1 were larger when only a single lag was reported than when estimates for multiple lags were reported; and heterogeneity of city-specific estimates in the meta-analysis were larger than with NMMAPS.
This study provides evidence of short-term associations between ozone and mortality as well as evidence of publication bias.
Ozone has been associated with various adverse health effects, including increased rates of hospital admissions and exacerbation of respiratory illnesses. Although numerous time-series studies have estimated associations between day-to-day variation in ozone levels and mortality counts, results have been inconclusive.
To investigate whether short-term (daily and weekly) exposure to ambient ozone is associated with mortality in the United States.
Design and Setting
Using analytical methods and databases developed for the National Morbidity, Mortality, and Air Pollution Study, we estimated a national average relative rate of mortality associated with short-term exposure to ambient ozone for 95 large US urban communities from 1987-2000. We used distributed-lag models for estimating community-specific relative rates of mortality adjusted for time-varying confounders (particulate matter, weather, seasonality, and long-term trends) and hierarchical models for combining relative rates across communities to estimate a national average relative rate, taking into account spatial heterogeneity.
Main Outcome Measure
Daily counts of total non–injury-related mortality and cardiovascular and respiratory mortality in 95 large US communities during a 14-year period.
A 10-ppb increase in the previous week’s ozone was associated with a 0.52% increase in daily mortality (95% posterior interval [PI], 0.27%-0.77%) and a 0.64% increase in cardiovascular and respiratory mortality (95% PI, 0.31%-0.98%). Effect estimates for aggregate ozone during the previous week were larger than for models considering only a single day’s exposure. Results were robust to adjustment for particulate matter, weather, seasonality, and long-term trends.
These results indicate a statistically significant association between short-term changes in ozone and mortality on average for 95 large US urban communities, which include about 40% of the total US population. The findings indicate that this widespread pollutant adversely affects public health.
Evidence on the health risks associated with short-term exposure to fine particles (particulate matter ≤2.5 μm in aerodynamic diameter [PM2.5]) is limited. Results from the new national monitoring network for PM2.5 make possible systematic research on health risks at national and regional scales.
To estimate risks of cardiovascular and respiratory hospital admissions associated with short-term exposure to PM2.5 for Medicare enrollees and to explore heterogeneity of the variation of risks across regions.
Design, Setting, and Participants
A national database comprising daily time-series data daily for 1999 through 2002 on hospital admission rates (constructed from the Medicare National Claims History Files) for cardiovascular and respiratory outcomes and injuries, ambient PM2.5 levels, and temperature and dew-point temperature for 204 US urban counties (population >200 000) with 11.5 million Medicare enrollees (aged >65 years) living an average of 5.9 miles from a PM2.5 monitor.
Main Outcome Measures
Daily counts of county-wide hospital admissions for primary diagnosis of cerebrovascular, peripheral, and ischemic heart diseases, heart rhythm, heart failure, chronic obstructive pulmonary disease, and respiratory infection, and injuries as a control outcome.
There was a short-term increase in hospital admission rates associated with PM2.5 for all of the health outcomes except injuries. The largest association was for heart failure, which had a 1.28% (95% confidence interval, 0.78%–1.78%) increase in risk per 10-μg/m3 increase in same-day PM2.5. Cardiovascular risks tended to be higher in counties located in the Eastern region of the United States, which included the Northeast, the Southeast, the Midwest, and the South.
Short-term exposure to PM2.5 increases the risk for hospital admission for cardiovascular and respiratory diseases.
A potential role for cardiovascular disease (CVD) risk factors in the aetiology of suicide has not been comprehensively examined. In addition to being small in scale and poorly characterized, existing studies very rarely sample Asian populations in whom risk factor–suicide relationships may plausibly differ to Caucasian groups. We examined the association between a series of CVD risk factors and future mortality from suicide.
Methods and results
The Korean Cancer Prevention Study is a prospective cohort study comprising 1 234 927 individuals (445 022 women) aged 30–95 years with extensive measurement of established CVD risk factors at baseline and subsequent mortality surveillance. Fourteen years of follow-up gave rise to 472 deaths (389 in men and 83 in women) from suicide. After adjustment for a range of covariates, in men, smoking hazard ratio; 95% CI: (current vs. never: 1.69; 1.27, 2.24), alcohol intake (1–24 g/day vs. none: 1.29; 1.00, 1.66), blood cholesterol (≥240 vs. <200 mg/dL: 0.54; 0.36, 0.80), body mass index (underweight vs. normal weight: 2.08; 1.26, 3.45), stature [quartile 1(lowest) vs. 4: 1.68; 1.23, 2.30], socioeconomic status [quartile 1(lowest) vs. 4: 1.65; 1.21, 2.24], and martial status (unmarried vs. other: 1.60; 0.83, 3.06) were related to suicide mortality risk. These associations were generally apparent in women, although of lower magnitude. Exercise and blood pressure were not associated with completed suicide.
In this cohort of Korean men and women, a series of CVD risk factors were associated with an elevated risk of future suicide mortality.
Cardiovascular disease; Risk factors; Epidemiology; Suicide
Epidemiologic evidence provides some support for a causal association between maternal secondhand smoke (SHS) exposure during pregnancy and reduction in infant birth weight. The purpose of this cross-sectional study is to examine the magnitude of this association in China, where both prevalence and dose of SHS exposure are thought to be higher than in U.S. populations. Women who gave birth in Beijing and Changchun September 2000–November 2001 were interviewed to quantify self-reported prenatal SHS exposure. Their medical records were reviewed for data on pregnancy complications and birth outcomes. Non-smoking women who delivered term babies (≥37 weeks gestation) were included in the study (N = 2,770). Nearly a quarter of the women (24%) reported daily SHS exposure, 47% reported no prenatal exposure, and 75% denied any SHS exposure from the husband smoking at home. Overall, no deficit in mean birth weight was observed with exposure from all sources of SHS combined (+11 grams, 95% CI: +2, +21). Infants had higher mean birth weights among the exposed than the unexposed for all measures of SHS exposure. Future studies on SHS exposure and infant birth weight in China should emphasize more objective measures of exposure to quantify and account for any exposure misclassification.
secondhand smoke; China; birth weight; pregnancy; perinatal; epidemiology
Exposure to particulate matter (PM) is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation.
We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC) barrier integrity and enhanced cardiopulmonary dysfunction.
Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER) in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm). Biochemical assessment of ROS generation and Ca2+ mobilization were also measured.
PM exposure induced tight junction protein Zona occludens-1 (ZO-1) relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin). N-acetyl-cysteine (NAC, 5 mM) reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2), in a ROS-dependent manner with subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro.
These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes.
Calpain; Endothelial permeability; Particulate matter; ROS; TRPM2
To further clarify the relationship between total cholesterol and cancer, which remains unclear.
We prospectively examined the association between total cholesterol and site-specific and all-cancer incidence among 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent a standardized biennial medical examination in 1992 to 1995 and were observed for 14 years until cancer diagnosis or death.
Over follow-up, 53,944 men and 24,475 women were diagnosed with a primary cancer. Compared with levels less than 160 mg/dL, high total cholesterol (≥ 240 mg/dL) was positively associated with prostate cancer (hazard ratio [HR], 1.24; 95% CI, 1.07 to 1.44; P trend = .001) and colon cancer (HR, 1.12; 95% CI, 1.00 to 1.25; P trend = .05) in men and breast cancer in women (HR, 1.17; 95% CI, 1.03 to 1.33; P trend = .03). Higher total cholesterol was associated with a lower incidence of liver cancer (men: HR, 0.42; 95% CI, 0.38 to 0.45; P trend < .001; women: HR, 0.32; 95% CI, 0.27 to 0.39; P trend < .001), stomach cancer (men: HR, 0.87; 95% CI, 0.82 to 0.93; P trend ≤ .001; women: HR, 0.86; 95% CI, 0.77 to 0.97; P trend = .06), and, in men, lung cancer (HR, 0.89; 95% CI, 0.82 to 0.96; P trend < .001). Results for liver cancer were slightly attenuated after additional adjustment for liver enzyme levels and hepatitis B surface antigen status (men: HR, 0.60; P trend < .001; women: HR, 0.46; P trend = .003) and exclusion of the first 10 years of follow-up (men: HR, 0.59; P trend < .001; women: HR, 0.44; P trend < .001). Total cholesterol was inversely associated with all-cancer incidence in both men (HR, 0.84; 95% CI, 0.81 to 0.86; P trend < .001) and women (HR, 0.91; 95% CI, 0.87 to 0.95; P trend < .001), but these associations were attenuated after excluding incident liver cancers (men: HR, 0.95; P trend < .001; women: HR, 0.98; P trend = .32).
In this large prospective study, we found that total cholesterol was associated with the risk of several different cancers, although these relationships differed markedly by cancer site.