Estimating the Independent Effects of Multiple Pollutants in the Presence of Measurement Error: An Application of a Measurement-Error–Resistant Technique

Misclassification of exposure usually leads to biased estimates of exposure–response associations. This is particularly an issue in cases with multiple correlated exposures, where the direction of bias is uncertain. It is necessary to address this problem when considering associations with important public health implications such as the one between mortality and air pollution, because biased exposure effects can result in biased risk assessments. The National Morbidity and Mortality Air Pollution Study (NMMAPS) recently reported results from an assessment of multiple pollutants and daily mortality in 90 U.S. cities. That study assessed the independent associations of the selected pollutants with daily mortality in two-pollutant models. Excess mortality was associated with particulate matter of aerodynamic diameter ≤10 μm/m(3) (PM(10)), but not with other pollutants, in these two pollutant models. The extent of bias due to measurement error in these reported results is unclear. Schwartz and Coull recently proposed a method that deals with multiple exposures and, under certain conditions, is resistant to measurement error. We applied this method to reanalyze the data from NMMAPS. For PM(10), we found results similar to those reported previously from NMMAPS (0.24% increase in deaths per 10-μg/m(3) increase in PM(10)). In addition, we report an important effect of carbon monoxide that had not been observed previously

The Effect of Particulate Air Pollution on Emergency Admissions for Myocardial Infarction: A Multicity Case-Crossover Analysis

Recently, attention has focused on whether particulate air pollution is a specific trigger of myocardial infarction (MI). The results of several studies of single locations assessing the effects of ambient particular matter on the risk of MI have been disparate. We used a multicity case-crossover study to examine risk of emergency hospitalization associated with fine particulate matter (PM) with aerodynamic diameter < 10 μm (PM(10)) for > 300,000 MIs during 1985–1999 among elderly residents of 21 U.S. cities. We used time-stratified controls matched on day of the week or on temperature to detect possible residual confounding by weather. Overall, we found a 0.65% [95% confidence interval (CI), 0.3–1.0%] increased risk of hospitalization for MI per 10 μg/m(3) increase in ambient PM(10) concentration. Matching on apparent temperature yielded a 0.64% increase in risk (95% CI, 0.1–1.2%). We found that the effect size for PM(10) doubled for subjects with a previous admission for chronic obstructive pulmonary disease or a secondary diagnosis of pneumonia, although these differences did not achieve statistical significance. There was a weaker indication of a larger effect on males but no evidence of effect modification by age or the other diagnoses. We also found that the shape of the exposure–response relationship between MI hospitalizations and PM(10) is almost linear, but with a steeper slope at levels of PM(10) < 50 μg/m(3). We conclude that increased concentrations of ambient PM(10) are associated with increased risk of MI among the elderly

Particulate Air Pollution, Progression, and Survival after Myocardial Infarction

OBJECTIVE: Several studies have examined the effect of particulate pollution (PM) on survival in general populations, but less is known about susceptible groups. Moreover, previous cohort studies have been cross-sectional and subject to confounding by uncontrolled differences between cities. DESIGN: We investigated whether PM was associated with progression of disease or reduced survival in a study of 196,000 persons from 21 U.S. cities discharged alive following an acute myocardial infarction (MI), using within-city between-year exposure to PM. We constructed city-specific cohorts of survivors of acute MI using Medicare data between 1985 and 1999, and defined three outcomes on follow-up: death, subsequent MI, and a first admission for congestive heart failure (CHF). Yearly averages of PM(10) (particulate matter with aerodynamic diameter < 10 μm) were merged to the individual annual follow-up in each city. We applied Cox’s proportional hazard regression model in each city, with adjustment for individual risk factors. In the second stage of the analysis, the city-specific results were combined using a meta-regression. RESULTS: We found significant associations with a hazard ratio for the sum of the distributed lags of 1.3 [95% confidence interval (CI), 1.2–1.5] for mortality, a hazard ratio of 1.4 (95% CI, 1.2–1.7) for a hospitalization for CHF, and a hazard ratio of 1.4 (95% CI, 1.1–1.8) for a new hospitalization for MI per 10 μg/m(3) PM(10). CONCLUSIONS: This is the first long-term study showing a significant association between particle exposure and adverse post-MI outcomes in persons who survived an MI

Air Pollution, Smoking, and Plasma Homocysteine

BACKGROUND: Mild hyperhomocysteinemia is independently associated with an increased risk of cardiovascular disease. Air pollution exposure induces short-term inflammatory changes that may determine hyperhomocysteinemia, particularly in the presence of a preexisting proinflammatory status such as that found in cigarette smokers. OBJECTIVE: We examined the relation of air pollution levels with fasting and postmethionine-load total homocysteine (tHcy) in 1,213 normal subjects from Lombardia, Italy. METHODS: We obtained hourly concentrations of particulate matter < 10 μm in aerodynamic diameter (PM(10)) and gaseous pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide(,) ozone) from 53 monitoring sites covering the study area. We applied generalized additive models to compute standardized regression coefficients controlled for age, sex, body mass index, smoking, alcohol, hormone use, temperature, day of the year, and long-term trends. RESULTS: The estimated difference in tHcy associated with an interquartile increase in average PM(10) concentrations in the 24 hr before the study was nonsignificant [0.4%; 95% confidence interval (CI), −2.4 to 3.3 for fasting; and 1.1%, 95% CI, −1.5 to 3.7 for postmethionine-load tHcy]. In smokers, 24-hr PM(10) levels were associated with 6.3% (95% CI, 1.3 to 11.6; p < 0.05) and 4.9% (95% CI, 0.5 to 9.6; p < 0.05) increases in fasting and postmethionine-load tHcy, respectively, but no association was seen in nonsmokers (p-interaction = 0.005 for fasting and 0.039 for postmethionine-load tHcy). Average 24-hr O(3) concentrations were associated with significant differences in fasting tHcy (6.7%; 95% CI, 0.9 to 12.8; p < 0.05), but no consistent associations were found when postmethionine-load tHcy and/or 7-day average O(3) concentrations were considered. CONCLUSIONS: Air particles may interact with cigarette smoking and increase plasma homocysteine in healthy subjects

Potential Role of Ultrafine Particles in Associations between Airborne Particle Mass and Cardiovascular Health

Numerous epidemiologic time-series studies have shown generally consistent associations of cardiovascular hospital admissions and mortality with outdoor air pollution, particularly mass concentrations of particulate matter (PM) ≤2.5 or ≤10 μm in diameter (PM(2.5), PM(10)). Panel studies with repeated measures have supported the time-series results showing associations between PM and risk of cardiac ischemia and arrhythmias, increased blood pressure, decreased heart rate variability, and increased circulating markers of inflammation and thrombosis. The causal components driving the PM associations remain to be identified. Epidemiologic data using pollutant gases and particle characteristics such as particle number concentration and elemental carbon have provided indirect evidence that products of fossil fuel combustion are important. Ultrafine particles < 0.1 μm (UFPs) dominate particle number concentrations and surface area and are therefore capable of carrying large concentrations of adsorbed or condensed toxic air pollutants. It is likely that redox-active components in UFPs from fossil fuel combustion reach cardiovascular target sites. High UFP exposures may lead to systemic inflammation through oxidative stress responses to reactive oxygen species and thereby promote the progression of atherosclerosis and precipitate acute cardiovascular responses ranging from increased blood pressure to myocardial infarction. The next steps in epidemiologic research are to identify more clearly the putative PM casual components and size fractions linked to their sources. To advance this, we discuss in a companion article (Sioutas C, Delfino RJ, Singh M. 2005. Environ Health Perspect 113:947–955) the need for and methods of UFP exposure assessment

That lung cancer incidence falls in ex-smokers: misconceptions 2

Misconceptions and ill-founded theories can arise in all areas of science. However, the apparent accessibility of many epidemiology findings and popular interest in the subject can lead to additional misunderstandings. The article below continues an occasional series of short editorials highlighting some current misinterpretations of epidemiological findings. Invited authors will be given wide scope in judging the prevalence of the misconception under discussion. We hope that this series will prove instructive to cancer researchers in other disciplines as well as to students of epidemiology. Adrian L Harris and Leo Kinle