David Q. Rich

Association of Air Pollution with Increased Incidence of Ventricular Tachyarrhythmias Recorded by Implanted Cardioverter Defibrillators

Epidemiologic studies have demonstrated a consistent link between sudden cardiac deaths and particulate air pollution. We used implanted cardioverter defibrillator (ICD) records of ventricular tachyarrhythmias to assess the role of air pollution as a trigger of these potentially life-threatening events. The study cohort consisted of 203 cardiac patients with ICD devices in the Boston metropolitan area who were followed for an average of 3.1 years between 1995 and 2002. Fine particle mass and gaseous air pollution plus temperature and relative humidity were measured on almost all days, and black carbon, sulfate, and particle number on a subset of days. Date, time, and intracardiac electrograms of ICD-detected arrhythmias were downloaded at the patients’ regular follow-up visits (about every 3 months). Ventricular tachyarrhythmias were identified by electrophysiologist review. Risk of ventricular arrhythmias associated with air pollution was estimated with logistic regression, adjusting for season, temperature, relative humidity, day of the week, patient, and a recent prior arrhythmia. We found increased risks of ventricular arrhythmias associated with 2-day mean exposure for all air pollutants considered, although these associations were not statistically significant. We found statistically significant associations between air pollution and ventricular arrhythmias for episodes within 3 days of a previous arrhythmia. The associations of ventricular tachyarrhythmias with fine particle mass, carbon monoxide, nitrogen dioxide, and black carbon suggest a link with motor vehicle pollutants. The associations with sulfate suggest a link with stationary fossil fuel combustion sources.

Maternal exposure to particulate air pollution and term birth weight : a multi-country evaluation of effect and heterogeneity

Background: A growing body of evidence has associated maternal exposure to air pollution with adverse effects on fetal growth; however, the existing literature is inconsistent. Objectives: We aimed to quantify the association between maternal exposure to particulate air pollution and term birth weight and low birth weight (LBW) across 14 centers from 9 countries, and to explore the influence of site characteristics and exposure assessment methods on between-center heterogeneity in this association. Methods: Using a common analytical protocol, International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) centers generated effect estimates for term LBW and continuous birth weight associated with PM10 and PM2.5 (particulate matter ≤ 10 and 2.5 µm). We used meta-analysis to combine the estimates of effect across centers (~ 3 million births) and used meta-regression to evaluate the influence of center characteristics and exposure assessment methods on between-center heterogeneity in reported effect estimates. Results: In random-effects meta-analyses, term LBW was positively associated with a 10-μg/m3 increase in PM10 [odds ratio (OR) = 1.03; 95% CI: 1.01, 1.05] and PM2.5 (OR = 1.10; 95% CI: 1.03, 1.18) exposure during the entire pregnancy, adjusted for maternal socioeconomic status. A 10-μg/m3 increase in PM10 exposure was also negatively associated with term birth weight as a continuous outcome in the fully adjusted random-effects meta-analyses (–8.9 g; 95% CI: –13.2, –4.6 g). Meta-regressions revealed that centers with higher median PM2.5 levels and PM2.5:PM10 ratios, and centers that used a temporal exposure assessment (compared with spatiotemporal), tended to report stronger associations. Conclusion: Maternal exposure to particulate pollution was associated with LBW at term across study populations. We detected three site characteristics and aspects of exposure assessment methodology that appeared to contribute to the variation in associations reported by centers.

Association Between Changes in Air Pollution Levels During the Beijing Olympics and Biomarkers of Inflammation and Thrombosis in Healthy Young Adults

CONTEXT Air pollution is a risk factor for cardiovascular diseases (CVD), but the underlying biological mechanisms are not well understood. OBJECTIVE To determine whether markers related to CVD pathophysiological pathways (biomarkers for systemic inflammation and thrombosis, heart rate, and blood pressure) are sensitive to changes in air pollution. DESIGN, SETTING, AND PARTICIPANTS Using a quasi-experimental opportunity offered by greatly restricted air pollution emissions during the Beijing Olympics, we measured pollutants daily and the outcomes listed below in 125 healthy young adults before, during, and after the 2008 Olympics (June 2-October 30). We used linear mixed-effects models to estimate the improvement in outcome levels during the Olympics and the anticipated reversal of outcome levels after pollution controls ended to determine whether changes in outcome levels were associated with changes in pollutant concentrations. MAIN OUTCOME MEASURES C-reactive protein (CRP), fibrinogen, von Willebrand factor, soluble CD40 ligand (sCD40L), soluble P-selectin (sCD62P) concentrations; white blood cell count (WBC); heart rate; and blood pressure. RESULTS Concentrations of particulate and gaseous pollutants decreased substantially (-13% to -60%) from the pre-Olympic period to the during-Olympic period. Using 2-sided tests conducted at the .003 level, we observed statistically significant improvements in sCD62P levels by -34.0% (95% CI, -38.4% to -29.2%; P < .001) from a pre-Olympic mean of 6.29 ng/mL to a during-Olympic mean of 4.16 ng/mL and von Willebrand factor by -13.1% (95% CI, -18.6% to -7.5%; P < .001) from 106.4% to 92.6%. After adjustments for multiple comparisons, changes in the other outcomes were not statistically significant. In the post-Olympic period when pollutant concentrations increased, most outcomes approximated pre-Olympic levels, but only sCD62P and systolic blood pressure were significantly worsened from the during-Olympic period. The fraction of above-detection-limit values for CRP (percentage ≥ 0.3 mg/L) was reduced from 55% in the pre-Olympic period to 46% in the during-Olympic period and reduced further to 36% in the post-Olympic period. Interquartile range increases in pollutant concentrations were consistently associated with statistically significant increases in fibrinogen, von Willebrand factor, heart rate, sCD62P, and sCD40L concentrations. CONCLUSIONS Changes in air pollution levels during the Beijing Olympics were associated with acute changes in biomarkers of inflammation and thrombosis and measures of cardiovascular physiology in healthy young persons. These findings are of uncertain clinical significance.

Increased Risk of Paroxysmal Atrial Fibrillation Episodes Associated with Acute Increases in Ambient Air Pollution

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 O3 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.

Heart Failure and the Risk of Shocks in Patients With Implantable Cardioverter Defibrillators Results From the Triggers Of Ventricular Arrhythmias (TOVA) Study

Background—Left ventricular ejection fraction (LVEF) predicts device discharges in patients with implantable cardioverter-defibrillators (ICDs). The relationship between severity of congestive heart failure (CHF) and ICD discharges is less clear. Methods and Results—We prospectively analyzed the association between CHF and risk of appropriate ICD discharges in the Triggers Of Ventricular Arrhythmias (TOVA) study, a cohort study of ICD patients conducted at 31 centers in the United States. Reported shocks were confirmed for sustained ventricular tachycardia (VT) or fibrillation (VF) by analysis of stored electrograms. Proportional hazards models included CHF categorized by New York Heart Association class. Baseline CHF was present among 502 (44%) of 1140 patients; 170 (34%) had class I, 230 (46%) had class II, 97 (19%) had class III, and only 5 (1%) had class IV symptoms. During median follow-up of 212 days, 92 patients experienced 1 or more appropriate ICD discharges. Class III CHF was associated in a statistically significantly manner with ICD discharge for VT/VF (hazard ratio 2.40, 95% CI 1.16 to 4.98), even with adjustment for LVEF. The combination of LVEF <0.20 and class III symptoms resulted in a particularly high risk of shocks for VT/VF (hazard ratio 3.90, 95% CI 1.28 to 11.92). Conclusions—Class III CHF, an easily accessible clinical measure, is an independent risk factor, along with LVEF, for ventricular arrhythmias that require shock therapy among ICD patients. Whether patients with class III CHF benefit to a greater degree from ICDs and whether aggressive treatment of CHF in ICD patients may prevent ventricular arrhythmias remains to be determined.

Inflammatory and Oxidative Stress Responses of Healthy Young Adults to Changes in Air Quality during the Beijing Olympics

RATIONALE Unprecedented pollution control actions during the Beijing Olympics provided a quasi-experimental opportunity to examine biologic responses to drastic changes in air pollution levels. OBJECTIVES To determine whether changes in levels of biomarkers reflecting pulmonary inflammation and pulmonary and systemic oxidative stress were associated with changes in air pollution levels in healthy young adults. METHODS We measured fractional exhaled nitric oxide, a number of exhaled breath condensate markers (H(+), nitrite, nitrate, and 8-isoprostane), and urinary 8-hydroxy-2-deoxyguanosine in 125 participants twice in each of the pre- (high pollution), during- (low pollution), and post-Olympic (high pollution) periods. We measured concentrations of air pollutants near where the participants lived and worked. We used mixed-effects models to estimate changes in biomarker levels across the three periods and to examine whether changes in biomarker levels were associated with changes in pollutant concentrations, adjusting for meteorologic parameters. MEASUREMENTS AND MAIN RESULTS From the pre- to the during-Olympic period, we observed significant and often large decreases (ranging from -4.5% to -72.5%) in levels of all the biomarkers. From the during-Olympic to the post-Olympic period, we observed significant and larger increases (48-360%) in levels of these same biomarkers. Moreover, increased pollutant concentrations were consistently associated with statistically significant increases in biomarker levels. CONCLUSIONS These findings support the important role of oxidative stress and that of pulmonary inflammation in mediating air pollution health effects. The findings demonstrate the utility of novel and noninvasive biomarkers in the general population consisting largely of healthy individuals.

Association of ventricular arrhythmias detected by implantable cardioverter defibrillator and ambient air pollutants in the St Louis, Missouri metropolitan area

Background: It has previously been reported that the risk of ventricular arrhythmias is positively associated with ambient air pollution among patients with implantable cardioverter defibrillators (ICD) in Boston. Aims: To assess the association of community exposures to air pollution with ventricular arrhythmias in a cohort of ICD patients in metropolitan St Louis, Missouri. Methods: ICD detected episodes reported during clinical follow up were abstracted and reviewed by an electrophysiologist to identify ventricular arrhythmias. A total of 139 ventricular arrhythmias were identified among 56 patients. A case-crossover design was used with control periods matched on weekday and hour of the day within the same calendar month. Conditional logistic regression models were adjusted for temperature, barometric pressure, and relative humidity in the 24 hours preceding the event. Results: There was a significant (24%, 95% CI 7% to 44%) increase in risk of ventricular arrhythmias associated with each 5 ppb increase in mean sulphur dioxide and non-significantly increased risk (22%, 95% CI −6% to 60%; and 18%, 95% CI −7% to 50%) associated with increases in nitrogen dioxide (6 ppb) and elemental carbon (0.5 μg/m3), respectively in the 24 hours before the arrhythmia. Conclusions: These results provide evidence of an association between ventricular arrhythmias and ambient air pollutants in St Louis. This is consistent with previous results from Boston, although the pollutants responsible for the increased risk are different.

Ambient air pollutant concentrations during pregnancy and the risk of fetal growth restriction

Background: Previous studies of air pollution and birth outcomes have not evaluated whether complicated pregnancies might be susceptible to the adverse effects of air pollution. It was hypothesised that trimester mean pollutant concentrations could be associated with fetal growth restriction, with larger risks among complicated pregnancies. Methods: A multiyear linked birth certificate and maternal/newborn hospital discharge dataset of singleton, term births to mothers residing in New Jersey at the time of birth, who were white (non-Hispanic), African–American (non-Hispanic) or Hispanic was used. Very small for gestational age (VSGA) was defined as a fetal growth ratio <0.75, small for gestational age (SGA) as ⩾0.75 and <0.85, and ‘reference’ births as ⩾0.85. Using polytomous logistic regression, associations between mean pollutant concentrations during the first, second and third trimesters and the risks of SGA/VSGA were examined, as well as effect modification of these associations by several pregnancy complications. Results: Significantly increased risk of SGA was associated with first and third trimester PM2.5 (particulate matter <2.5 μm in aerodynamic diameter), and increased risk of VSGA associated with first, second and third trimester nitrogen dioxide (NO2) concentrations. Pregnancies complicated by placental abruption and premature rupture of the membrane had ∼two- to fivefold greater excess risks of SGA/VSGA than pregnancies not complicated by these conditions, although these estimates were not statistically significant. Conclusions: These findings suggest that ambient air pollution, perhaps specifically traffic emissions during early and late pregnancy and/or factors associated with residence near a roadway during pregnancy, may affect fetal growth. Further, pregnancy complications may increase susceptibility to these effects in late pregnancy.

Increased ultrafine particles and carbon monoxide concentrations are associated with asthma exacerbation among urban children

OBJECTIVES Increased air pollutant concentrations have been linked to several asthma-related outcomes in children, including respiratory symptoms, medication use, and hospital visits. However, few studies have examined effects of ultrafine particles in a pediatric population. Our primary objective was to examine the effects of ambient concentrations of ultrafine particles on asthma exacerbation among urban children and determine whether consistent treatment with inhaled corticosteroids could attenuate these effects. We also explored the relationship between asthma exacerbation and ambient concentrations of accumulation mode particles, fine particles (≤2.5 micrograms [μm]; PM2.5), carbon monoxide, sulfur dioxide, and ozone. We hypothesized that increased 1-7 day concentrations of ultrafine particles and other pollutants would be associated with increases in the relative odds of an asthma exacerbation, but that this increase in risk would be attenuated among children receiving school-based corticosteroid therapy. METHODS We conducted a pilot study using data from 3 to 10 year-old children participating in the School-Based Asthma Therapy trial. Using a time-stratified case-crossover design and conditional logistic regression, we estimated the relative odds of a pediatric asthma visit treated with prednisone (n=96 visits among 74 children) associated with increased pollutant concentrations in the previous 7 days. We re-ran these analyses separately for children receiving medications through the school-based intervention and children in a usual care control group. RESULTS Interquartile range increases in ultrafine particles and carbon monoxide concentrations in the previous 7 days were associated with increases in the relative odds of a pediatric asthma visit, with the largest increases observed for 4-day mean ultrafine particles (interquartile range=2088p/cm(3); OR=1.27; 95% CI=0.90-1.79) and 7-day mean carbon monoxide (interquartile range=0.17ppm; OR=1.63; 95% CI=1.03-2.59). Relative odds estimates were larger among children receiving school-based inhaled corticosteroid treatment. We observed no such associations with accumulation mode particles, black carbon, fine particles (≤2.5μm), or sulfur dioxide. Ozone concentrations were inversely associated with the relative odds of a pediatric asthma visit. CONCLUSIONS These findings suggest a response to markers of traffic pollution among urban asthmatic children. Effects were strongest among children receiving preventive medications through school, suggesting that this group of children was particularly sensitive to environmental triggers. Medication adherence alone may be insufficient to protect the most vulnerable from environmental asthma triggers. However, further research is necessary to confirm this finding.

Are Ambient Ultrafine, Accumulation Mode, and Fine Particles Associated with Adverse Cardiac Responses in Patients Undergoing Cardiac Rehabilitation?

Background: Mechanisms underlying previously reported air pollution and cardiovascular (CV) morbidity associations remain poorly understood. Objectives: We examined associations between markers of pathways thought to underlie these air pollution and CV associations and ambient particle concentrations in postinfarction patients. Methods: We studied 76 patients, from June 2006 to November 2009, who participated in a 10-week cardiac rehabilitation program following a recent (within 3 months) myocardial infarction or unstable angina. Ambient ultrafine particle (UFP; 10–100 nm), accumulation mode particle (AMP; 100–500 nm), and fine particle concentrations (PM2.5; ≤ 2.5 μm in aerodynamic diameter) were monitored continuously. Continuous Holter electrocardiogram (ECG) recordings were made before and during supervised, graded, twice weekly, exercise sessions. A venous blood sample was collected and blood pressure was measured before sessions. Results: Using mixed effects models, we observed adverse changes in rMSSD [square root of the mean of the sum of the squared differences between adjacent normal-to-normal (NN) intervals], SDNN (standard deviation of all NN beat intervals), TpTe (time from peak to end of T-wave), heart rate turbulence, systolic and diastolic blood pressures, C-reactive protein, and fibrinogen associated with interquartile range increases in UFP, AMP, and PM2.5 at 1 or more lag times within the previous 5 days. Exposures were not associated with MeanNN, heart-rate–corrected QT interval duration (QTc), deceleration capacity, and white blood cell count was not associated with UFP, AMP, and PM2.5 at any lag time. Conclusions: In cardiac rehabilitation patients, particles were associated with subclinical decreases in parasympathetic modulation, prolongation of late repolarization duration, increased blood pressure, and systemic inflammation. It is possible that such changes could increase the risk of CV events in this susceptible population.