Person:

Mittleman, Murray

Background: The effects of weather on West Nile virus (WNV) mosquito populations in the United States have been widely reported, but few studies assess their overall impact on transmission to humans. Objectives: We investigated meteorologic conditions associated with reported human WNV cases in the United States. Methods: We conducted a case–crossover study to assess 16,298 human WNV cases reported to the Centers for Disease Control and Prevention from 2001 to 2005. The primary outcome measures were the incidence rate ratio of disease occurrence associated with mean weekly maximum temperature, cumulative weekly temperature, mean weekly dew point temperature, cumulative weekly precipitation, and the presence of ≥ 1 day of heavy rainfall (≥ 50 mm) during the month prior to symptom onset. Results: Increasing weekly maximum temperature and weekly cumulative temperature were similarly and significantly associated with a 35–83% higher incidence of reported WNV infection over the next month. An increase in mean weekly dew point temperature was significantly associated with a 9–38% higher incidence over the subsequent 3 weeks. The presence of at least 1 day of heavy rainfall within a week was associated with a 29–66% higher incidence during the same week and over the subsequent 2 weeks. A 20-mm increase in cumulative weekly precipitation was significantly associated with a 4–8% increase in incidence of reported WNV infection over the subsequent 2 weeks. Conclusions: Warmer temperatures, elevated humidity, and heavy precipitation increased the rate of human WNV infection in the United States independent of season and each others’ effects.

Background: Although patients with heart failure (HF) have been identified as particularly susceptible to the acute effects of air pollution, the effects of long-term exposure to air pollution on patients with this increasingly prevalent disease are largely unknown. Objective: This study was designed to examine the mortality risk associated with residential exposure to traffic-related air pollution among HF patients. Methods: A total of 1,389 patients hospitalized with acute HF in greater Worcester, Massachusetts, during 2000 were followed for survival through December 2005. We used daily traffic within 100 and 300 m of residence as well as the distance from residence to major roadways and to bus routes as proxies for residential exposure to traffic-related air pollution. We assessed mortality risks for each exposure variable using Cox proportional hazards models adjusted for prognostic factors. Results: After the 5-year follow-up, only 334 (24%) subjects were still alive. An interquartile range increase in daily traffic within 100 m of home was associated with a mortality hazard ratio (HR) of 1.15 [95% confidence interval (CI), 1.05–1.25], whereas for traffic within 300 m this association was 1.09 (95% CI, 1.01–1.19). The mortality risk decreased with increasing distance to bus routes (HR = 0.88; 95% CI, 0.81–0.96) and was larger for those living within 100 m of a major roadway or 50 m of a bus route (HR = 1.30; 95% CI, 1.13–1.49). Adjustment for area-based income and educational level slightly attenuated these associations. Conclusions: Residential exposure to traffic-related air pollution increases the mortality risk after hospitalization with acute HF. Reducing exposure to traffic-related emissions may improve the long-term prognosis of HF patients.

Background and Objective: RESPIRE, a randomized trial of an improved cookstove, was conducted in Guatemala to assess health effects of long-term reductions in wood smoke exposure. Given the evidence that ambient particles increase blood pressure, we hypothesized that the intervention would lower blood pressure. Methods: Two study designs were used: a) between-group comparisons based on randomized stove assignment, and b) before-and-after comparisons within subjects before and after they received improved stoves. From 2003 to 2005, we measured personal fine particle (particulate matter with aerodynamic diameter < 2.5 μm; PM2.5) exposures and systolic (SBP) and diastolic blood pressure (DBP) among women > 38 years of age from the chimney woodstove intervention group (49 subjects) and traditional open wood fire control group (71 subjects). Measures were repeated up to three occasions. Results: Daily average PM2.5 exposures were 264 and 102 μg/m3 in the control and intervention groups, respectively. After adjusting for age, body mass index, an asset index, smoking, secondhand tobacco smoke, apparent temperature, season, day of week, time of day, and a random subject intercept, the improved stove intervention was associated with 3.7 mm Hg lower SBP [95% confidence interval (CI), −8.1 to 0.6] and 3.0 mm Hg lower DBP (95% CI, −5.7 to −0.4) compared with controls. In the second study design, among 55 control subjects measured both before and after receiving chimney stoves, similar associations were observed. Conclusion: The between-group comparisons provide evidence, particularly for DBP, that the chimney stove reduces blood pressure, and the before-and-after comparisons are consistent with this evidence.

Background: Fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] has been associated with autonomic dysregulation.Objective We hypothesized that PM2.5 influences postural changes in systolic blood pressure (ΔSBP) and in diastolic blood pressure (ΔDBP) and that this effect is modified by genes thought to be related to chronic lung disease. Methods: We measured blood pressure in participants every 3–5 years. ΔSBP and ΔDBP were calculated as sitting minus standing SBP and DBP. We averaged PM2.5 over 48 hr before study visits and analyzed 202 single nucleotide polymorphisms (SNPs) in 25 genes. To address multiple comparisons, data were stratified into a split sample. In the discovery cohort, the effects of SNP × PM2.5 interactions on ΔSBP and ΔDBP were analyzed using mixed models with subject-specific random intercepts. We defined positive outcomes as p < 0.1 for the interaction; we analyzed only these SNPs in the replicate cohort and confirmed them if p < 0.025 with the same sign. Confirmed associations were analyzed within the full cohort in models adjusted for anthropometric and lifestyle factors. Results: Nine hundred forty-five participants were included in our analysis. One interaction with rs9568232 in PHD finger protein 11 (PHF11) was associated with greater ΔDBP. Interactions with rs1144393 in matrix metalloprotease 1 (MMP1) and rs16930692, rs7955200, and rs10771283 in inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) were associated with significantly greater ΔSBP. Because SNPs associated with ΔSBP in our analysis are in genes along the renin–angiotensin pathway, we then examined medications affecting that pathway and observed significant interactions for angiotensin receptor blockers but not angiotensin-converting enzyme inhibitors with PM2.5. Conclusions: PM2.5 influences blood pressure and autonomic function. This effect is modified by genes and drugs that also act along this pathway.

OBJECTIVE—To study whether obese individuals, who are at higher risk for diabetes and disparities in care than nonobese individuals, are more likely to have undiagnosed diabetes. RESEARCH DESIGN AND METHODS—We performed an analysis of 5,514 adult participants in the 1999–2004 National Health and Nutrition Examination Survey. Particpants were interviewed about sociodemographic and medical data, including whether they had been diagnosed with diabetes, and were examined for height, weight, and fasting plasma glucose level ≥126 mg/dl or by previous physician diagnosis. After categorizing participants into normal weight, overweight, and obese according to BMI, the prevalance and diagnosis of diabetes across BMI categories was compared using χ2. RESULTS—Of the 9.8% (weighted sample) of participants who had diabetes, based on fasting glucose levels and self-reported diagnosis, 28.1% were undiagnosed, translating to an estimated 5.2 million people in the U.S. population. The proportion undiagnosed was not significantly different among normal-weight (22.2%), overweight (32.5%), or obese adults (27.4%). Nevertheless, obese adults comprise more than half of the undiagnosed diabetes cases (2.7 million). Relative to normal-weight adults, the adjusted odds ratio (OR) for having undiagnosed diabetes was 1.50 (0.73–3.08) in overweight and 1.37 (0.72–2.63) in obese adults. CONCLUSIONS—Despite a higher underlying risk of diabetes and widespread clinical recognition of this higher risk, obesity does not increase the likelihood that an individual's diabetes will be diagnosed.

Background: Long-term exposure to particulate air pollution has been associated with an increased risk of dying from cardiopulmonary and ischemic heart disease, yet few studies have evaluated cardiovascular end points other than mortality. We investigated the relationship between long-term exposure to traffic and occurrence of acute myocardial infarction (AMI) in a case–control study. Methods: A total of 5,049 confirmed cases of AMI were identified between 1995 and 2003 as part of the Worcester Heart Attack Study, a community-wide study examining changes over time in the incidence of AMI among greater Worcester, Massachusetts, residents. Population controls were selected from Massachusetts resident lists. We used cumulative traffic within 100 m of subjects’ residence and distance from major roadway as proxies for exposure to traffic-related air pollution. We estimated the relationship between exposure to traffic and occurrence of AMI using logistic regression, and we adjusted for the following potential confounders: age, sex, section of the study area, point sources emissions of particulate matter with aerodynamic diameter < 2.5 μm, area socioeconomic characteristics, and percentage of open space. Results: An increase in cumulative traffic near the home was associated with a 4% increase in the odds of AMI per interquartile range [95% confidence interval (CI), 2–7%], whereas living near a major roadway was associated with a 5% increase in the odds of AMI per kilometer (95% CI, 3–6%). Conclusions: These results provide support for an association between long-term exposure to traffic and the risk of AMI.

Objectives: We reported previously that 24-hr moving average ambient air pollution concentrations were positively associated with ventricular arrhythmias detected by implantable cardioverter defibrillators (ICDs). ICDs also detect paroxysmal atrial fibrillation episodes (PAF) that result in rapid ventricular rates. In this same cohort of ICD patients, we assessed the association between ambient air pollution and episodes of PAF. Design: We performed a case–crossover study. Participants: Patients who lived in the Boston, Massachusetts, metropolitan area and who had ICDs implanted between June 1995 and December 1999 (n = 203) were followed until July 2002. Evaluations/Measurements: We used conditional logistic regression to explore the association between community air pollution and 91 electrophysiologist-confirmed episodes of PAF among 29 subjects. Results: We found a statistically significant positive association between episodes of PAF and increased ozone concentration (22 ppb) in the hour before the arrhythmia (odds ratio = 2.08; 95% confidence interval = 1.22, 3.54; p = 0.001). The risk estimate for a longer (24-hr) moving average was smaller, thus suggesting an immediate effect. Positive but not statistically significant risks were associated with fine particles, nitrogen dioxide, and black carbon. Conclusions: Increased ambient O(_3) pollution was associated with increased risk of episodes of rapid ventricular response due to PAF, thereby suggesting that community air pollution may be a precipitant of these events.

Background: Extreme temperatures have been associated with hospitalization and death among individuals with heart failure, but few studies have explored the underlying mechanisms. Objectives: We hypothesized that outdoor temperature in the Boston, Massachusetts, area (1- to 4-day moving averages) would be associated with higher levels of biomarkers of inflammation and myocyte injury in a repeated-measures study of individuals with stable heart failure. Methods: We analyzed data from a completed clinical trial that randomized 100 patients to 12 weeks of tai chi classes or to time-matched education control. B-type natriuretic peptide (BNP), C-reactive protein (CRP), and tumor necrosis factor (TNF) were measured at baseline, 6 weeks, and 12 weeks. Endothelin-1 was measured at baseline and 12 weeks. We used fixed effects models to evaluate associations with measures of temperature that were adjusted for time-varying covariates. Results: Higher apparent temperature was associated with higher levels of BNP beginning with 2-day moving averages and reached statistical significance for 3- and 4-day moving averages. CRP results followed a similar pattern but were delayed by 1 day. A 5°C change in 3- and 4-day moving averages of apparent temperature was associated with 11.3% [95% confidence interval (CI): 1.1, 22.5; :p = 0.03) and 11.4% (95% CI: 1.2, 22.5; p = 0.03) higher BNP. A 5°C change in the 4-day moving average of apparent temperature was associated with 21.6% (95% CI: 2.5, 44.2; p = 0.03) higher CRP. No clear associations with TNF or endothelin-1 were observed. Conclusions: Among patients undergoing treatment for heart failure, we observed positive associations between temperature and both BNP and CRP—predictors of heart failure prognosis and severity.

Background: Human controlled-exposure studies have assessed the impact of ambient fine particulate matter on cardiac autonomic function measured by heart rate variability (HRV), but whether these effects are modified by concomitant ozone exposure remains unknown. Objective: In this study we assessed the impact of O(_3) and particulate matter exposure on HRV in humans. Methods: In a crossover design, 50 subjects (19–48 years of age) were randomized to 2-hr controlled exposures to filtered air (FA), concentrated ambient particles (CAPs), O(_3), or combined CAPs and ozone (CAPs + O(_3)). The primary end point was change in HRV between the start and end of exposure. Secondary analyses included blood pressure (BP) responses, and effect modification by asthmatic status. Results: Achieved mean CAPs and O(_3) exposure concentrations were 121.6 ± 48.0 μg/m(^3) and 113.9 ± 6.6 ppb, respectively. In a categorical analysis, exposure had no consistent effect on HRV indices. However, the dose–response relationship between CAPs mass concentration and HRV indices seemed to vary depending on the presence of O(_3). This heterogeneity was statistically significant for the low-frequency component of HRV (p = 0.02) and approached significance for the high-frequency component and time-domain measures of HRV. Exposure to CAPs + O(_3) increased diastolic BP by 2.0 mmHg (SE, 1.2; p = 0.02). No other statistically significant changes in BP were observed. Asthmatic status did not modify these effects. Conclusion: The potentiation by O(_3) of CAPs effects on diastolic BP and possibly HRV is of small magnitude in young adults. Further studies are needed to assess potential effects in more vulnerable populations.

Background: Diabetes increases the risk of hypertension and orthostatic hypotension and raises the risk of cardiovascular death during heat waves and high pollution episodes. Objective: We examined whether short-term exposures to air pollution (fine particles, ozone) and heat resulted in perturbation of arterial blood pressure (BP) in persons with type 2 diabetes mellitus (T2DM). Methods: We conducted a panel study in 70 subjects with T2DM, measuring BP by automated oscillometric sphygmomanometer and pulse wave analysis every 2 weeks on up to five occasions (355 repeated measures). Hourly central site measurements of fine particles, ozone, and meteorology were conducted. We applied linear mixed models with random participant intercepts to investigate the association of fine particles, ozone, and ambient temperature with systolic, diastolic, and mean arterial BP in a multipollutant model, controlling for season, meteorological variables, and subject characteristics. Results: An interquartile increase in ambient fine particle mass [particulate matter (PM) with an aerodynamic diameter of (\leq) 2.5 (\mu)m (PM(_{2.5}))] and in the traffic component black carbon in the previous 5 days (3.54 and 0.25 (\mu)g/m(^3), respectively) predicted increases of 1.4 mmHg [95% confidence interval (CI): 0.0, 2.9 mmHg] and 2.2 mmHg (95% CI: 0.4, 4.0 mmHg) in systolic BP (SBP) at the population geometric mean, respectively. In contrast, an interquartile increase in the 5-day mean of ozone (13.3 ppb) was associated with a 5.2 mmHg (95% CI: –8.6, –1.8 mmHg) decrease in SBP. Higher temperatures were associated with a marginal decrease in BP. Conclusions: In subjects with T2DM, PM was associated with increased BP, and ozone was associated with decreased BP. These effects may be clinically important in patients with already compromised autoregulatory function.