Leukocyte Traits and Exposure to Ambient Particulate Matter Air Pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study

Abstract

Background: Inflammatory effects of ambient particulate matter (PM) air pollution exposures may underlie PM-related increases in cardiovascular disease risk and mortality, although evidence of PM-associated leukocytosis is inconsistent and largely based on small, cross-sectional, and/or unrepresentative study populations.

Objectives: Our objective was to estimate PM-leukocyte associations among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities study ($n=\mathrm{165,675}$).

Methods: We based the PM-leukocyte estimations on up to four study visits per participant, at which peripheral blood leukocytes and geocoded address-specific concentrations of $\mathrm{PM}\le 10$, $\le 2.5$, and $2.5-10\mu m$ in diameter (${\mathrm{PM}}_{10}$, ${\mathrm{PM}}_{2.5}$, and ${\mathrm{PM}}_{2.5-10}$, respectively) were available. We multiply imputed missing data using chained equations and estimated PM-leukocyte count associations over daily to yearly PM exposure averaging periods using center-specific, linear, mixed, longitudinal models weighted for attrition and adjusted for sociodemographic, behavioral, meteorological, and geographic covariates. In a subset of participants with available data ($n=\mathrm{8,457}$), we also estimated PM-leukocyte proportion associations in compositional data analyses.

Results: We found a $12\text{cells}/\mu L$ (95% confidence interval: $-9$, 33) higher leukocyte count, a 1.2% (0.6%, 1.8%) higher granulocyte proportion, and a $-1.1\%$ ($-1.9\%$, $-0.3\%$) lower $\text{CD}{8}^{+}$ T-cell proportion per $10{\text{-}\mu g/m}^3$ increase in 1-month mean ${\mathrm{PM}}_{2.5}$. However, shorter-duration ${\mathrm{PM}}_{10}$ exposures were inversely and only modestly associated with leukocyte count.

Discussion: The ${\mathrm{PM}}_{2.5}$-leukocyte estimates, albeit imprecise, suggest that among racially, ethnically, and environmentally diverse U.S. populations, sustained, ambient exposure to fine PM may induce subclinical, but epidemiologically important, inflammatory effects. https://doi.org/10.1289/EHP5360.

Figure 1.

Map of geocoded Women’s Health Initiative (1993–2002) and Atherosclerosis Risk in Communities (1986–1998) study participants and centers at baseline. WHI centers ($n=39$) followed 1,238–3,690 participants. ARIC centers followed 3,588–3,943 participants. WHI and ARIC centers were co-located in Minneapolis, MN, and Winston-Salem, NC.

Figure 2.

Pooled difference in leukocyte count ($\mathrm{\Delta }$; $\text{cells}/\mathrm{\mu }\mathrm{L}$) per $10{\text{-}\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$ increase in PM concentrations among $n=\mathrm{165,675}$ participants, Women’s Health Initiative (1993–2002) and Atherosclerosis Risk in Communities (1986–1998) study. Model 1 adjusted for race/ethnicity, age, sex (in ARIC), randomly assigned treatment group (in WHI), mean temperature, mean dew point, mean barometric pressure, season, and a restricted cubic natural spline function of calendar date with one knot per year. Model 2 adjusted for all covariates in Model 1 plus individual-level education and neighborhood socioeconomic status. Model 3 adjusted for all covariates in Model 2 plus smoking status, alcohol use, body mass index, and physical activity.

Figure 3.

Pooled difference in leukocyte composition ($\mathrm{\Delta }$; %) per $10{\text{-}\mathrm{\mu }\mathrm{g}/\mathrm{m}}^3$ increase in (A) 1- and (B) 12-month mean ${\mathrm{PM}}_{2.5}$ concentrations among $n=\mathrm{8,457}$ participants, Women’s Health Initiative (1993–2002) and Atherosclerosis Risk in Communities (1990–1995) study. Model 1 adjusted for race/ethnicity, age, sex (in ARIC), randomly assigned treatment group (in WHI), mean temperature, mean dew point, mean barometric pressure, season, and subpopulation-specific covariates. Model 2 also adjusted for individual-level education and neighborhood socioeconomic status. Model 3 additionally adjusted for smoking status, alcohol use, body mass index, and physical activity.