Triggering of ST-elevation myocardial infarction by ultrafine particles in New York: Changes following Tier 3 vehicle introduction.

BACKGROUND: Previously, we found increased rates of ST-elevation myocardial infarction (STEMI) associated with increased ultrafine particle (UFP; <100 nm) concentrations in the previous few hours in Rochester, New York. Relative rates were higher after air quality policies and a recession reduced pollutant concentrations (2014-2016 versus 2005-2013), suggesting PM composition had changed and the same PM mass concentration had become more toxic. Tier 3 light duty vehicles, which should produce less primary organic aerosols and oxidizable gaseous compounds, likely making PM less toxic, were introduced in 2017. Thus, we hypothesized we would observe a lower relative STEMI rate in 2017-2019 than 2014-2016. METHODS: Using STEMI events treated at the University of Rochester Medical Center (2014-2019), UFP and other pollutants measured in Rochester, a case-crossover design, and conditional logistic regression models, we estimated the rate of STEMI associated with increased UFP and other pollutants in the previous hours and days in the 2014-2016 and 2017-2019 periods. RESULTS: An increased rate of STEMI was associated with each 3111 particles/cm3 increase in UFP concentration in the previous hour in 2014-2016 (lag hour 0: OR = 1.22; 95% CI = 1.06, 1.39), but not in 2017-2019 (OR = 0.94; 95% CI = 0.80, 1.10). There were similar patterns for black carbon, UFP11-50nm, and UFP51-100nm. In contrast, increased rates of STEMI were associated with each 0.6 ppb increase in SO2 concentration in the previous 120 h in both periods (2014-2016: OR = 1.26, 95% CI = 1.03, 1.55; 2017-2019: OR = 1.21, 95% CI = 0.87, 1.68). CONCLUSIONS: Greater rates of STEMI were associated with short term increases in concentrations of UFP and other motor vehicle related pollutants before Tier 3 introduction (2014-2016), but not afterwards (2017-2019). This change may be due to changes in PM composition after Tier 3 introduction, as well as to increased exposure misclassification and greater underestimation of effects from 2017 to 2019.

Associations between Source-Specific Particulate Matter and Respiratory Infections in New York State Adults.

The response of respiratory infections to source-specific particulate matter (PM) is an area of active research. Using source-specific PM2.5 concentrations at six urban sites in New York State, a case-crossover design, and conditional logistic regression, we examined the association between source-specific PM and the rate of hospitalizations and emergency department (ED) visits for influenza or culture-negative pneumonia from 2005 to 2016. There were at most N = 14 764 influenza hospitalizations, N = 57 522 influenza ED visits, N = 274 226 culture-negative pneumonia hospitalizations, and N = 113 997 culture-negative pneumonia ED visits included in our analyses. We separately estimated the rate of respiratory infection associated with increased concentrations of source-specific PM2.5, including secondary sulfate (SS), secondary nitrate (SN), biomass burning (BB), pyrolyzed organic carbon (OP), road dust (RD), residual oil (RO), diesel (DIE), and spark ignition vehicle emissions (GAS). Increased rates of ED visits for influenza were associated with interquartile range increases in concentrations of GAS (excess rate [ER] = 9.2%; 95% CI: 4.3%, 14.3%) and DIE (ER = 3.9%; 95% CI: 1.1%, 6.8%) for lag days 0-3. There were similar associations between BB, SS, OP, and RO, and ED visits or hospitalizations for influenza, but not culture-negative pneumonia hospitalizations or ED visits. Short-term increases in PM2.5 from traffic and other combustion sources appear to be a potential risk factor for increased rates of influenza hospitalizations and ED visits.

Changes in the hospitalization and ED visit rates for respiratory diseases associated with source-specific PM2.5 in New York State from 2005 to 2016.

Prior work found increased rates for emergency department (ED) visits for asthma and hospitalizations for chronic obstructive pulmonary disease per unit mass of PM2.5 across New York State (NYS) during 2014-2016 after significant reductions in ambient PM2.5 concentrations had occurred following implementation of various policy actions and major economic disruptions. The associations of source-specific PM2.5 concentrations with these respiratory diseases were assessed with a time-stratified case-cossover design and logistic regression models to identify the changes in the PM2.5 that have led to the apparently increased toxicity per unit mass. The rates of ED visits and hospitalizations for asthma and COPD associated with increases in source-specific PM2.5 concentrations in the prior 1, 4, and 7 days were estimated for 6 urban sites in New York State. Overall, there were similar numbers of significantly increased (n = 9) and decreased rates (n = 8) of respiratory events (asthma and COPD hospitalizations and ED visits) associated with increased source-specific PM2.5 concentrations in the previous 1, 4, and 7 days. Associations of source-specific PM2.5 concentrations with excess rates of hospitalizations for COPD for spark- and compression ignition vehicles increased in the 2014-2016 period, but the values were not statistically significant. Other source types showed inconsistent patterns of excess rates. For asthma ED visits, only biomass burning and road dust showed consistent positive associations with road dust having significant values for most lag times. Secondary nitrate also showed significant positive associations with asthma ED visits in the AFTER period compared to no associations in the prior periods. These results suggest that the relationships of asthma and COPD exacerbation with source-specific PM2.5 are not well defined and further work will be needed to determine the causes of the apparent increases in the per unit mass toxicity of PM2.5 in New York State in the 2014-16 period.

Exploring the science, safety, and benefits of air care products: perspectives from the inaugural air care summit.

Seventy-one percent of US households purchase air care products. Air care products span a diverse range of forms, including scented aerosol sprays, pump sprays, diffusers, gels, candles, and plug-ins. These products are used to eliminate indoor malodors and to provide pleasant scent experiences. The use of air care products can lead to significant benefits as studies have shown that indoor malodor can cause adverse effects, negatively impacting quality of life, hygiene, and the monetary value of homes and cars, while disproportionately affecting lower income populations. Additionally, studies have also shown that scent can have positive benefits related to mood, stress reduction, and memory enhancement among others. Despite the positive benefits associated with air care products, negative consumer perceptions regarding the safety of air care products can be a barrier to their use. During the inaugural Air Care Summit, held on 18 May 2018 in the Washington, DC, metropolitan area, multidisciplinary experts including industry stakeholders, academics, and scientific and medical experts were invited to share and assess the existing data related to air care products, focusing on ingredient and product safety and the benefits of malodor removal and scent. At the Summit's completion, a panel of independent experts representing the fields of pulmonary medicine, medical and clinical toxicology, pediatric toxicology, basic science toxicology, occupational dermatology and experimental psychology convened to review the data presented, identify potential knowledge gaps, and suggest future research directions to further assess the safety and benefits of air care products.

Refractory ceramic fibers: Fiber characteristics, potential health effects and clinical observations.

Refractory ceramic fibers (RCFs) are amorphous fibers that belong to a class of materials termed synthetic vitreous fibers (SVFs), also called man-made mineral fibers (MMMFs), which includes alkaline earth silicate wool, glass wool, rock (stone) wool, slag wool, and special-purpose glass fibers. RCFs are more durable and biopersistent than several other SVFs, although very much less biopersistent than either amosite or crocidolite asbestos. Chronic inhalation studies indicated that rats and hamsters exposed to RCF fibers developed fibrosis and tumors. Epidemiological studies at the University of Cincinnati funded by the Industry indicated that exposed workers; (1) exhibited symptoms (e.g., dyspnea) similar to those reported in other dust-exposed populations, (2) developed statistically, but not clinically, significant deficits in certain measures of pulmonary function in a cross sectional study, but no excessive decline in a longitudinal study, and (3) a dose related increase in pleural plaques, but no interstitial fibrosis. The 2003 mortality study indicated no incremental lung cancer and no cases of mesothelioma. RCF producers developed a comprehensive industry wide product stewardship program (PSP) beginning in the late 1980s. In conjunction with the PSP, there has been a progressive decrease in the TWA concentration of fibers by manufacturers and end-users. The research program has successfully produced more soluble fibers and undertaken efforts to develop larger diameter fibers. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer.

Review of refractory ceramic fiber (RCF) toxicity, epidemiology and occupational exposure.

This literature review on refractory ceramic fibers (RCF) summarizes relevant information on manufacturing, processing, applications, occupational exposure, toxicology and epidemiology studies. Rodent toxicology studies conducted in the 1980s showed that RCF caused fibrosis, lung cancer and mesothelioma. Interpretation of these studies was difficult for various reasons (e.g. overload in chronic inhalation bioassays), but spurred the development of a comprehensive product stewardship program under EPA and later OSHA oversight. Epidemiology studies (both morbidity and mortality) were undertaken to learn more about possible health effects resulting from occupational exposure. No chronic animal bioassay studies on RCF have been conducted since the 1980s. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer. Evidence supporting a finding that urinary tumors are associated with RCF exposure remains, but is weaker. One reported, but unconfirmed, mesothelioma was found in an individual with prior occupational asbestos exposure. An elevated SMR for leukemia was found, but was absent in the highly exposed group and has not been observed in studies of other mineral fibers. The industry will continue the product stewardship program including the mortality study.

Associations between ambient wood smoke and other particulate pollutants and biomarkers of systemic inflammation, coagulation and thrombosis in cardiac patients.

BACKGROUND: Increased particulate air pollution has been associated with both an increased risk of myocardial infarction (MI) and adverse changes in cardiac biomarkers. Up to 30% of ambient wintertime fine particles (PM2.5) in Rochester, NY are from wood burning. Our study examined associations between ambient levels of a marker of wood smoke (Delta-C) and other particulate air pollutants and biomarkers of inflammation, coagulation and thrombosis. METHODS: We measured blood concentrations of C-reactive protein (CRP), D-dimer, fibrinogen, P-selectin, platelet factor 4 (PF-4), von Willebrand factor (vWF), and myeloperoxidase (MPO) of 135 patients undergoing cardiac catheterization during the winters of 2011-2013. We coupled these data with hourly ambient concentrations of Delta-C, black carbon (BC; marker of traffic pollution), and ultrafine (10-100nm; UFP), accumulation mode (100-500nm; AMP), and fine particles (<2.5µm; PM2.5). Using linear regression models, we estimated the change in each biomarker associated with increased pollutant concentrations at intervals between 1 and 96h preceding blood collection. RESULTS: Each 0.13µg/m3 increase in Delta-C concentration in the prior 12h was associated with a 0.91% increase in fibrinogen levels (95% CI=0.23%, 1.59%), but unexpectedly in the prior 48h, each 0.17µg/m3 increase in Delta-C concentration was associated with a 2.75% decrease in MPO levels (95% CI=-5.13%,-0.37%). We did not see associations between Delta-C concentrations and any other biomarkers. Interquartile range (IQR) increases in PM2.5, BC, UFP, and AMP concentrations were generally associated with increased CRP and fibrinogen, but not PF4, D-dimer, vWF, or P-selectin. CONCLUSIONS: In a population of cardiac patients, we noted adverse changes in fibrinogen associated with increased concentrations of a marker of wood smoke. Increases in PM2.5, BC, AMP, and UFP concentrations in the previous 96h were also associated with adverse changes in markers of systemic inflammation and coagulation, but not with markers of endothelial cell dysfunction or platelet activation.

Does total antioxidant capacity modify adverse cardiac responses associated with ambient ultrafine, accumulation mode, and fine particles in patients undergoing cardiac rehabilitation?

BACKGROUND: Previous studies suggest that pathways reducing oxidative stress may have a protective effect against adverse cardiac responses associated with ambient PM. However, few studies have directly assessed total antioxidant capacity (TAC) as a potential effect modifier of cardiac responses to increased ambient PM. OBJECTIVES: We examined if TAC modifies the association between ambient PM and markers of heart rate variability (HRV), repolarization, systemic inflammation, and systolic blood pressure (SBP) in post-infarction patients. METHODS: We recruited 76 patients with a recent coronary event (myocardial infarction or unstable angina) who participated in a cardiac rehabilitation program from June 2006 to November 2009 in Rochester, New York. Ambient fine particle (PM2.5,≤2.5µm in aerodynamic diameter), accumulation mode particle (AMP, 100-500nm) and ultrafine particle (UFP, 10-100nm) concentrations were measured continuously by fixed-site monitors. Markers of HRV and repolarization were measured by continuous Holter electrocardiogram (ECG) recordings before and during exercise sessions of the rehabilitation program. Blood pressure was measured and venous blood samples were collected before exercise to measure TAC and inflammation markers. We applied linear mixed models to assess changes in markers of HRV, repolarization, systemic inflammation, and SBP associated with increased PM concentrations in the low, medium and high TAC tertile groups, after adjusting for covariates including temperature, calendar time since the beginning of the study, visit number, month of year, and hour of day. RESULTS: Based on subject-visits with available TAC, we observed increases in SBP, C-reactive protein, and fibrinogen, and decreases in rMSSD (square root of the mean of the sum of the squared differences between adjacent normal to normal intervals) and SDNN (standard deviation of normal to normal beat intervals) associated with increased PM2.5, AMP and UFP in the previous 6-120h (e.g. change in SBP associated with each interquartile range (IQR) increase in PM2.5 lagged 0-5h was 1.27mmHg [95%CI: 0.09, 2.46mmHg]). However, we did not observe a consistent pattern of effect measure modification by TAC for any combination of pollutant and outcome (e.g. changes in SBP associated with each IQR increase in PM2.5 lagged 0-5h for the low, medium and high TAC tertile groups were 1.93mmHg [95%CI: 0.23, 3.63 mmHg], -0.31 mmHg [95%CI: -2.62, 2.01 mmHg], and 1.29mmHg [95%CI: -0.64, 3.21 mmHg], respectively. P for interaction=0.28). CONCLUSIONS: In a post-infarction population, total antioxidant capacity does not appear to modify the association between biomarkers of heart rate variability, repolarization, systemic inflammation, and systolic blood pressure and ambient PM concentrations in the previous 6-120h.

Ambient and Controlled Particle Exposures as Triggers for Acute ECG Changes.

INTRODUCTION: Previous studies have examined changes in heart rate variability (HRV*) and repolarization associated with increased particulate matter (PM) concentrations on the same and previous few days. However, few studies have examined whether these health responses to PM occur within a few hours or even less. Moreover, it is not clear whether exposure of subjects to ambient or-controlled PM concentrations both lead to similar health effects or whether any of the subjects' individual characteristics modify any of their responses to PM. The aims of the cur- rent study were to investigate whether exposure to PM was associated with rapid changes (< 60 minutes or con- current hour up to a delay of 6 hours) in markers of car- diac rhythni or changes in total antioxidant capacity (a marker of protection against oxidative stress) and whether any PM effects on cardiac rhythm markers were modified by total antioxidant capacity, age, obesity, smoking, hypertension, exertion, prior myocardial infarction (MI), or medication. METHODS: We obtained data from a completed study in Augsburg, Germany (a panel study in N= 109 subjects, including a group with type 2 diabetes or impaired glucose tolerance [IGT; also known as prediabetes]) and a group of other- wise healthy subjects with a potential genetic susceptibil- ity to detoxifying and inflammatory pathways (Hampel et al. 2012b), as well as three completed studies in Rochester, New York (the REHAB panel study of N= 76 postinfarction patients in a cardiac rehabilitation pro- gram [Rich et al. 2012b]; the UPDIABETES study of con- trolled exposure to ultrafine particles [UFPs, particles with an aerodynamic diameter < 100 nm] of N = 19 patients with type 2 diabetes [Stewart et al. 2010; Vora et al. 2014j; and the UPCON controlled-exposure study of concentrated UFP exposure in N = 20 young, healthy, life- time nonsmokers). Data included 5-minute and 1-hour values for HRV and repolarization parameters from elec- trocardiogram (ECG) recordings and total antioxidant capacity measured in stored blood samples. Ambient con- centrations of UFPs, accumulation-mode particles (AMP, particles with an aerodynamic diameter of 100-500 nm), fine PM (PM2.5, particles with an aerodynamic diameter 2.5 pm), and black carbon (BC) were also available. We first conducted factor analyses in each study to find subgroups of correlated ECG outcomes and to reduce the number of outcomes examined in our statistical models. We then restricted the statistical analyses to the factors and representative.outcomes that were common to all four studies, including total HRV (measured as the standard deviation of normal-to-normal [NN] beat intervals [SDNNj), parasympathetic modulation (measured as the root mean square of the successive differences [RMSSD between adjacent NN beat intervals), and T-wave morphol- ogy (measured as T-wave complexity). Next, we used addi- tive mixed models to estimate the change in each outcome associated with increased pollutant concentrations in the . concurrent and previous 6 hours and with 5-minute inter- vals up to the previous 60 minutes, accounting for the correlation of repeated outcome measures for each subject and adjusting for time trend, hour of the day, temperature, relative humidity, day of the week, month, and visit number. Because multiple comparisons were an issue in our. analyses, we used a discovery-and-replication approach to draw conclusions across studies for each research question. RESULTS: In the Augsburg study, interquartile range (IQR) increases in UFP concentrations lagged 2 to 5 hours were associated with 1%-3% decreases in SDNN (e.g., lagged 3 hours in the group with a genetic susceptibility: -2.26%; 95% confidence interval [CI], -3.98% to -0.53%). In the REHAB study, similarly, IQR increases in UFP concentra- tions in the previous 5 hours were associated with < 3% decreases in SDNN (e.g., lagged 1 hour: -2.69%; 95% CI, -5.13% to -0.26%). We also found decreases in SDNN associated with IQR increases in total particle count-(a surrogate for UFP) in the UPDIABETES study (lagged 1 hour: -13.22%; 95% CI, -24.11% to -2.33%) but not in the UPCON study. In the Augsburg study, IQR increases in PM2.5 concen- trations in the concurrent hour and lagged 1-5 hours, AMP concentrations lagged 1 and 3 hours, and BC con- centrations lagged 1-5 hours were associated with -1%-5% decreases in SDNN (e.g., PM2.5 lagged 2 hours in the group with diabetes or IGT: -4.59%; 95% CI, -7.44% to -1.75%). In the REHAB study, IQR increases in PM2.5 concentrations lagged 5 and 6 hours and AMP concentra- tions in the concurrent hour and lagged up to 5 hours were associated with 1%-2% decreases in SDNN (e.g., PM2.5 lagged 4 hours: -2.13%; 95% CI, -3.91% to -0.35%). In the Augsburg study, IQR increases in PM2.5 concen- trations in the concurrent hour and BC lagged 1 and 6 hours were associated with 3%-7% decreases in RMSSD (e.g., PM2.5 concurrent hour in the group with diabetes or IGT: -7.20%; 95% CI, -12.11% to -2.02%). In the REHAB study, similarly, increases in PM2.5 concen- trations lagged 4 to 6 hours-though not AMP or BC con- centrations at any lag hour-were associated with -2.5%-3.5% decreases in RMSSD (e.g., PM2.5 lagged 5 hours: -3.49%; 95% CI, -6.13% to -0.84%). We did not find consistent evidence of any pollutant effects on T-wave complexity in 1-hour recordings. For 5-minute record- ings, there was no consistent evidence of UFP effects on SDNN, RMSSD, or T-wave complexity at any 5-minute interval within 60 minutes. We further concluded that these replicated hourly effects of UFP and PM2.5 on short-term measures of SDNN and RMSSD generally did not differ between the groups in the studies (i.e., type 2 diabetes, pre-diabetes/IGT, post- infarction, and healthy subjects). Last, we found no con- sistent evidence of effects of any pollutant on total anti- oxidant capacity and no consistent evidence of modification of our PM2.5-outcome associations by any of the potential effect modifiers. ONCLUSIONS: Increased UFP concentrations were associated with decreased SDNN in both of the panel studies and one of the two controlled-exposure studies. We also found that decreased SDNN was associated with both increased PM2.5 and AMP concentrations in the previous 6 hours in the panel studies and that decreased RMSSD was associ- ated with increased PM2.5 concentrations in the previous 6 hours in the panel studies. We therefore concluded that the research questions were replicated. Our findings suggest that both UFPs and PM2.5 are associated with autonomic dysfunction within hours of exposure, which may in part. explain the previously reported risk of acute cardiovascular events associated with increased PM in the previous few hours. Despite the heterogeneity of the study populations,and protocols, our findings provided consistent evidence for the induction of rapid pathophysiological responses by UFPs and PM2.5- The absence of consistent associations between UFPs, PM2.5, and these outcomes when examining shorter time intervals indicates that the 5- to 60-minute responses may be less pronounced than the responses occurring within hours. However, the findings from the 5-minute intervals may have been affected by the variety of proto- cols and conditions from study to study as well as by the potential effects of underlying diseases (e.g., healthy indi- viduals versus individuals with diabetes or a recent cor- onary artery. event), physical activity, circadian rhythms, stress, and/or medications.

Triggering of myocardial infarction by increased ambient fine particle concentration: Effect modification by source direction.

BACKGROUND: Previously, we reported a 18% increased odds of ST-elevation myocardial infarction (STEMI) associated with each 7.1 µg/m(3) increase in PM2.5 concentration in the hour prior to MI onset. We found no association with non-ST elevation myocardial infarction (NSTEMI). We examined if this association was modified by PM2.5 source direction. METHODS: We used the NOAA HYbrid Single-Particle Lagrangian Trajectory (HYSPLIT) model to calculate each hourly air mass location for the 24 hours before each case or control time period in our previous PM2.5/STEMI case-crossover analysis. Using these data on patients with STEMI (n=338), hourly PM2.5 concentrations, and case-crossover methods, we evaluated whether our PM2.5/STEMI association was modified by whether the air mass passed through each of the 8 cardinal wind direction sectors in the previous 24h. RESULTS: When the air mass passed through the West-Southwest direction (WSW) any time in the past 24h, the odds of STEMI associated with each 7.1µg/m(3) increase in PM2.5 concentration in the previous hour (OR=1.27; 95% CI=1.08, 1.22) was statistically significantly (p=0.01) greater than the relative odds of STEMI associated with increased PM2.5 concentration when the wind arrived from any other direction (OR=0.99; 95% CI=0.80, 1.22). We found no other effect modification by any other source direction. Further, relative odds estimates were largest when the time spent in the WSW was 8-16 h, compared to ≤7 h or 17-24 h, suggesting that particles arising from sources in this direction were more potent in triggering STEMIs. CONCLUSIONS: Since relative odds estimates were higher when the air mass passed through the WSW octant in the past 24h, there may be specific components of the ambient aerosol that are more potent in triggering STEMIs. This direction is associated with substantial emissions from coal-fired power plants and other industrial sources of the Ohio River Valley, many of which are undergoing modifications to reduce their emissions.

Are pleural plaques an appropriate endpoint for risk analyses?

This review summarizes the literature on the relation between the development of pleural plaques and non-malignant and malignant disease in cohorts exposed to asbestos and other fibers. The available evidence indicates that, absent any other pleural disease, the presence of pleural plaques does not result in respiratory symptoms or clinically significant impacts on lung function. For certain types of asbestos, the development of pleural plaques is statistically correlated with malignant disease, but the evidence is consistent with the hypothesis that pleural plaques without other pleural disease are a marker of exposure, rather than an independent risk factor. Pleural plaques have also developed in cohorts exposed to other fibers that have not proven to be carcinogenic. Risk analyses should be based on the avoidance of known adverse conditions, rather than pleural plaques per se.

Systematic review of pleural plaques and lung function.

CONTEXT: US EPA proposed a Reference Concentration for Libby amphibole asbestos based on the premise that pleural plaques are adverse and cause lung function deficits. OBJECTIVE: We conducted a systematic review to evaluate whether there is an association between pleural plaques and lung function and ascertain whether results were dependent on the method used to identify plaques. METHODS: Using the PubMed database, we identified studies that evaluated pleural plaques and lung function. We assessed each study for quality, then integrated evidence and assessed associations based on the Bradford Hill guidelines. We also compared the results of HRCT studies to those of X-ray studies. RESULTS: We identified 16 HRCT and 36 X-ray studies. We rated six HRCT and 16 X-ray studies as higher quality based on a risk-of-bias analysis. Half of the higher quality studies reported small but statistically significant mean lung function decrements associated with plaques. None of the differences were clinically significant. Many studies had limitations, such as inappropriate controls and/or insufficient adjustment for confounders. There was little consistency in the direction of effect for the most commonly reported measurements. X-ray results were more variable than HRCT results. Pleural plaques were not associated with changes in lung function over time in longitudinal studies. CONCLUSION: The weight of evidence indicates that pleural plaques do not impact lung function. Observed associations are most likely due to unidentified abnormalities or other factors.

Cardiovascular effects of ozone in healthy subjects with and without deletion of glutathione-S-transferase M1.

CONTEXT: Exposure to ozone has acute respiratory effects, but few human clinical studies have evaluated cardiovascular effects. OBJECTIVE: We hypothesized that ozone exposure alters pulmonary and systemic vascular function, and cardiac function, with more pronounced effects in subjects with impaired antioxidant defense from deletion of the glutathione-S-transferase M1 gene (GSTM1 null). METHODS: Twenty-four young, healthy never-smoker subjects (12 GSTM1 null) inhaled filtered air, 100 ppb ozone and 200 ppb ozone for 3 h, with intermittent exercise, in a double-blind, randomized, crossover fashion. Exposures were separated by at least 2 weeks. Vital signs, spirometry, arterial and venous blood nitrite levels, impedance cardiography, peripheral arterial tonometry, estimation of pulmonary capillary blood volume (Vc), and blood microparticles and platelet activation were measured at baseline and during 4 h after each exposure. RESULTS: Ozone inhalation decreased lung function immediately after exposure (mean ± standard error change in FEV1, air: -0.03 ± 0.04 L; 200 ppb ozone: -0.30 ± 0.07 L; p < 0.001). The immediate post-exposure increase in blood pressure, caused by the final 15-min exercise period, was blunted by 200 ppb ozone exposure (mean ± standard error change for air: 16.7 ± 2.6 mmHg; 100 ppb ozone: 14.5 ± 2.4 mmHg; 200 ppb ozone: 8.5 ± 2.5 mmHg; p = 0.02). We found no consistent effects of ozone on any other measure of cardiac or vascular function. All results were independent of the GSTM1 genotype. CONCLUSIONS: We did not find convincing evidence for early acute adverse cardiovascular consequences of ozone exposure in young healthy adults. The ozone-associated blunting of the blood pressure response to exercise is of unclear clinical significance.

Inhalation of ultrafine carbon particles alters heart rate and heart rate variability in people with type 2 diabetes.

BACKGROUND: Diabetes may confer an increased risk for the cardiovascular health effects of particulate air pollution, but few human clinical studies of air pollution have included people with diabetes. Ultrafine particles (UFP, ≤100 nm in diameter) have been hypothesized to be an important component of particulate air pollution with regard to cardiovascular health effects. METHODS: 17 never-smoker subjects 30-60 years of age, with stable type 2 diabetes but otherwise healthy, inhaled either filtered air (0-10 particles/cm3) or elemental carbon UFP (~107 particles/cm3, ~50 ug/m3, count median diameter 32 nm) by mouthpiece, for 2 hours at rest, in a double-blind, randomized, crossover study design. A digital 12-lead electrocardiogram (ECG) was recorded continuously for 48 hours, beginning 1 hour prior to exposure. RESULTS: Analysis of 5-minute segments of the ECG during quiet rest showed reduced high-frequency heart rate variability with UFP relative to air exposure (p = 0.014), paralleled by non-significant reductions in time-domain heart rate variability parameters. In the analysis of longer durations of the ECG, we found that UFP exposure increased the heart rate relative to air exposure. During the 21- to 45-hour interval after exposure, the average heart rate increased approximately 8 beats per minute with UFP, compared to 5 beats per minute with air (p = 0.045). There were no UFP effects on cardiac rhythm or repolarization. CONCLUSIONS: Inhalation of elemental carbon ultrafine particles alters heart rate and heart rate variability in people with type 2 diabetes. Our findings suggest that effects may occur and persist hours after a single 2-hour exposure.

Ambient fine particulate air pollution triggers ST-elevation myocardial infarction, but not non-ST elevation myocardial infarction: a case-crossover study.

BACKGROUND: We and others have shown that increases in particulate air pollutant (PM) concentrations in the previous hours and days have been associated with increased risks of myocardial infarction, but little is known about the relationships between air pollution and specific subsets of myocardial infarction, such as ST-elevation myocardial infarction (STEMI) and non ST-elevation myocardial infarction (NSTEMI). METHODS: Using data from acute coronary syndrome patients with STEMI (n = 338) and NSTEMI (n = 339) and case-crossover methods, we estimated the risk of STEMI and NSTEMI associated with increased ambient fine particle (<2.5 um) concentrations, ultrafine particle (10-100 nm) number concentrations, and accumulation mode particle (100-500 nm) number concentrations in the previous few hours and days. RESULTS: We found a significant 18% increase in the risk of STEMI associated with each 7.1 µg/m³ increase in PM2.5 concentration in the previous hour prior to acute coronary syndrome onset, with smaller, non-significantly increased risks associated with increased fine particle concentrations in the previous 3, 12, and 24 hours. We found no pattern with NSTEMI. Estimates of the risk of STEMI associated with interquartile range increases in ultrafine particle and accumulation mode particle number concentrations in the previous 1 to 96 hours were all greater than 1.0, but not statistically significant. Patients with pre-existing hypertension had a significantly greater risk of STEMI associated with increased fine particle concentration in the previous hour than patients without hypertension. CONCLUSIONS: Increased fine particle concentrations in the hour prior to acute coronary syndrome onset were associated with an increased risk of STEMI, but not NSTEMI. Patients with pre-existing hypertension and other cardiovascular disease appeared particularly susceptible. Further investigation into mechanisms by which PM can preferentially trigger STEMI over NSTEMI within this rapid time scale is needed.

Screening tests: a review with examples.

Screening tests are widely used in medicine to assess the likelihood that members of a defined population have a particular disease. This article presents an overview of such tests including the definitions of key technical (sensitivity and specificity) and population characteristics necessary to assess the benefits and limitations of such tests. Several examples are used to illustrate calculations, including the characteristics of low dose computed tomography as a lung cancer screen, choice of an optimal PSA cutoff and selection of the population to undergo mammography. The importance of careful consideration of the consequences of both false positives and negatives is highlighted. Receiver operating characteristic curves are explained as is the need to carefully select the population group to be tested.

Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers.

In 2011, SCOEL classified RCF as a secondary genotoxic carcinogen and supported a practical threshold. Inflammation was considered the predominant manifestation of RCF toxicity. Intrapleural and intraperitoneal implantation induced mesotheliomas and sarcomas in laboratory animals. Chronic nose-only inhalation bioassays indicated that RCF exposure in rats increased the incidence of lung cancer and similar exposures resulted in mesothelioma in hamsters, but these studies may have been compromised by overload. Epidemiological studies in the US and Europe showed an association between exposure and prevalence of respiratory symptoms and pleural plaques, but no interstitial fibrosis, mesotheliomas, or increased numbers of lung tumors were observed. As the latency of asbestos induced mesotheliomas can be up to 50 years, the relationship between RCF exposure and respiratory malignances has not been fully determined. Nonetheless, it is possible to offer useful perspectives. RCF and rock wool have similar airborne fiber dimensions and biopersistence. Therefore, it is likely that these fibers have similar toxicology. Traditional rock wool has been the subject of numerous cohort and case control studies. For rock wool, IARC (2002) concluded that the epidemiological studies did not provide evidence of carcinogenicity. Based on analogies with rock wool (read across), it is reasonable to believe that increases in lung cancer or any mesotheliomas are unlikely to be found in the RCF-exposed cohort. RCF producers have developed a product stewardship program to measure and control fiber concentrations and to further understand the health status of their workers.

Wollastonite toxicity: an update.

This review updates earlier work addressing the epidemiology and toxicity of wollastonite. Earlier chronic animal bioassay and human mortality data were inadequate (IARC term) or negative and no new studies of these types have been published. Wollastonite has been determined to have low biopersistence in both in vivo and in vitro studies, which probably accounts for its relative lack of toxicity. Earlier morbidity studies of mining/mineral processing facilities in Finland and New York State indicated that exposure to wollastonite might result in pleural plaques (Finland) or decrements in certain measures of lung function (New York). More recent analysis of data from an ongoing health surveillance program at one facility (New York) indicates that there are no pleural plaques or interstitial lung disease or decrements in lung function among never smokers or former smokers occupationally exposed to wollastonite. This result probably reflects continued reduction in exposures as part of an ongoing product stewardship program at this facility and suggests that wollastonite has relatively low toxicity as currently managed.