Particulate matter components, sources, and health: Systematic approaches to testing effects

Figures & data

Table 1. Broad overview of NPACT study designs

Study Approach	Lippmann et al.	Vedal et al.
Exposure timescales	Short- and long-term	Long-term only
Health endpoints	Respiratory and cardiovascular	Cardiovascular only
Epidemiologic Studies
Study design	Multicity time-series analysis and one cohort	Two cohorts
Health endpoints	Acute: respiratory and cardiovascular mortality and hospitalizationsChronic: mortality	Chronic: Subclinical markers of atherosclerosis; cardiovascular disease events (including mortality)
PM components and exposure assessment	EPA CSN monitors; MSA averages; sources	Cohort-specific and EPA CSN and IMPROVE monitors; individual-level exposure predictions; two exposure models; focus on OC, EC, silicon, and sulfur; included some evaluation of other pollutants and PM components
Source apportionment goal	Assessing exposure	Interpretation of exposure health effect estimates
Toxicologic Studies
Study design	ApoE knockout mouse model (normal diet); 6-month exposures; FVB/N mice; 12-day and 100-day exposures	ApoE knockout mouse model (high-fat/ high-cholesterol diet); 50-day exposure
Biologic endpoints	Cardiovascular effects and markers of oxidative stress and inflammation	Vascular effects and markers of oxidative stress and inflammation
Animal and cell culture exposures	Concentrated ambient particles (in vivo) and ambient particles collected on filters (in vitro and in vivo); five air sheds	Laboratory-generated complex mixtures: combinations of mixed vehicle emissions and non-vehicular primary particles (in vivo)

Notes: ApoE = apolipoprotein E; CSN = Chemical Speciation Network; EC = elemental carbon; EPA = U.S. Environmental Protection Agency; IMPROVE = Interagency Monitoring of Protected Visual Environments; MSA = metropolitan statistical area; OC = organic carbon; PM = particulate matter.

Table 2. Approaches and key findings of the epidemiologic studies^a,b

Study Approach	New York University/Ito		New York University/Thurston	University of Washington/Vedal^c
Study design	Time series (short-term)		Cohort (long-term)	Cohort (long-term)		Cohort (long-term)
Population	U.S. MSAs		ACS CPS-II cohort	MESA		WHI-OS
Cities	150 cities		100 cities	6 cities		45 cities
Participants	Population >100 million		~450,000 people	~6,800 people		~90,000 people
Health endpoints	Hospitalization	Mortality	Mortality	CIMT	CAC	Time to first event (MI, stroke, cardiac procedures, and CVD deaths)	Mortality
PM components and source categories associated with health outcomes	Cold season: PM2.5, NO2, CO, EC, OC, and Cu	Warm season: PM2.5, NO3, and sulfate	Components: PM2.5, As, Se, sulfur, Cl, Fe, Pb, and EC	Best evidence for OC and sulfur; little evidence for EC or silicon; some evidence for Cu	Some evidence for OC only	Best evidence for sulfur and less for OC; little evidence for EC or silicon	Best evidence for OC and less for sulfur; little evidence for EC or silicon
	Modified^d by PM2.5: Cu, Ni, and V	Modified^d by PM2.5: sulfate	Not associated: OC, silicon, and K
	Sources: vehicle exhaust	Sources: secondary aerosols	Source categories: coal combustion and possibly traffic; little evidence for soil or biomass combustion

Notes: ^aACS CPS-II = American Cancer Society Cancer Prevention Study II; As = arsenic; CAC = coronary artery calcification; Cl = chlorine; CIMT = carotid intima-media thickness; CO = carbon monoxide; Cu = copper; CVD = cardiovascular disease; EC = elemental carbon; Fe = iron; K = potassium; MESA = Multi-Ethnic Study of Atherosclerosis; MI = myocardial infarction; MSA = metropolitan statistical area; Ni = nickel; NO₂ = nitrogen dioxide; NO₃ = nitrate; OC = organic carbon; Pb = lead; PM = particulate matter; PM_2.5 = particulate matter <2.5 µm in aerodynamic diameter; Se = selenium; V = vanadium; WHI-OS = Women’s Health Initiative—Observational Study. ^bEpidemiologic studies at New York University were headed by George Thurston and Kazuhiko Ito and at the University of Washington by Sverre Vedal. ^cSource apportionment results supported the focus on four main components for evaluation in the Vedal study: EC and OC as markers of vehicle exhaust and other combustion emissions; OC also as a marker of secondary organic aerosol; silicon as a marker of crustal PM; and sulfur as a marker of secondary PM. ^dRisk estimates for these components were substantially modified when PM_2.5 was included in a two-pollutant model.

Table 3. Approaches and key findings of the toxicologic studies^a,b

Study Approach	New York University/Chen		New York University/Gordeon		University of Washington/Campen
Study design	Short-term (daily time-series)	Long-term (6 months)	Short-term (12 days)	Long-term (100 days)	Medium-term (50 days)
Exposures	Inhalation of CAPs at five locations (Manhattan, Tuxedo, East Lansing, Seattle, and Irvine)		Aspiration of PM collected on filters at five locations (Manhattan, Tuxedo, Ann Arbor, Seattle, and Los Angeles area); three size fractions		Inhalation of combinations of MVE or MVE gases with non-vehicular PM2.5 (sulfate, nitrate, or road dust)
PM concentrations	60–138 μg/m3		In vitro: 50–100 μg/mL		100 or 300 μg/m3
			In vivo: 50 μg
Model	ApoE knockout mice (normal diet)		FVB/N mice; epithelial cells, endothelial cells, cardiomyocytes	FVB/N mice	ApoE knockout mice (high-fat/highcholesterol diet)
	Heart rate and heart rate variability	Aorta plaque growth; serum biomarkers; heart rate and heart rate variability	Mice: lung inflammation	Lung inflammation	Aorta: lipid peroxidation, vascular function and remodeling, plaque growth and inflammation
			Cells: viability, ROS, inflammatory markers, beat frequency
PM components and sources associated with biologic findings	Effects after exposure to Ni (residual oil combustion) > to Al, EC, and P (traffic) > to sulfur (coal combustion) > to PM2.5	Plaque growth in Tuxedo, Manhattan, and East Lansing, but not in Irvine and Seattle; attributed to coal combustion	Complex interaction of particle size and composition (location and season); nothing ruled out	Source apportionment not reported	Effects after exposure to MVE > to MVE gases; fewer effects of nitrate and sulfate; no effects of road dust
					Effects after exposure to non-vehicular PM combined with MVE > non-vehicular PM without MVE

Notes: ^aAl = aluminum; CAPs = concentrated ambient particles; MVE = mixed vehicular engine emissions; Ni = nickel; P = phosphorus; PM = particulate matter; ROS = reactive oxygen species. ^bToxicologic studies at New York University were headed by Lung-Chi Chen and by Terry Gordon and for the University of Washington study by Matthew Campen at the University of New Mexico and Jacob McDonald at the Lovelace Respiratory Research Institute