International Journal of Hygiene and Environmental Health
C-reactive protein (CRP) and long-term air pollution with a focus on ultrafine particles
Introduction
According to the WHO, ambient air pollution contributed to 3.7 million premature deaths in 2012 worldwide including 280,000 in high-income countries of Europe and is therefore the largest environmental contributor to the burden of disease (Cohen et al., 2017). This risk factor particularly affects cardiovascular and cerebrovascular causes of death since these account for 80% of mortality attributable to ambient air pollution (WHO, 2014; Lim et al., 2012). Previous studies provide consistent evidence that long-term exposure to particulate matter (PM) air pollution is associated with cardiovascular morbidity and mortality (Brook et al., 2010; Newby et al., 2015). Although the exact mechanisms behind these effects are still unclear, an inflammatory response has been hypothesized to play an important role which is also supported by several animal studies (Upadhyay et al., 2010; Araujo et al., 2008). C‐reactive protein (CRP) is a reliable measure indicating systemic inflammation and high sensitivity (hs) CRP has also been reported to be a predictor for an increased risk of cardiovascular diseases (CVD) (Koenig et al., 2006).
Several epidemiological studies have reported associations of long-term exposure to air pollution with an increased level of CRP (Ostro et al., 2014; Hennig et al., 2014; Hoffmann et al., 2009) while others did not see an association (Dabass et al., 2016; Michikawa et al., 2016). A recent review on PM and hs-CRP did not find conclusive evidence yet (Li et al., 2012). However, previous studies mainly focused on larger particles like PM2.5 or PM10 (particulate matter with a size of <2.5 μm in aerodynamic diameter or <10 μm, respectively) whereas ultrafine particles (<100 nm) came into focus only recently. They are hypothesized to be more harmful than other particles (Delfino et al., 2005). Due to their small size they might even translocate from the lungs into the circulation which could directly lead to systemic inflammation (Araujo and Nel, 2009). Furthermore, their large surface may provide a mechanism for delivering much more potentially toxic absorbed organic material (Li et al., 2002). The California Teachers Study by Ostro et al. (Ostro et al., 2015) was the first study which investigated long-term effects of ultrafine particles on health and it prospectively included more than 100,000 participants. They reported a significant association of long-term exposure to ultrafine particles with all-cause and cardiovascular mortality. So far, only two studies have examined the association between long-term exposure to particle number concentration (PNC), as a proxy for ultrafine particles, and hs‐CRP. Viehmann et al. (2015) examined a population based prospective cohort study incorporating approximately 4800 participants finding a non-significant association whereas Lane et al. (2016) investigated 409 participants with regard to long-term exposure of near-highway ultrafine particle exposure in a cross-sectional design. The study rom the U.S. (Lane et al., 2016) also found a positive but non-significant association among all participants which even reached significance when including only the white non-Hispanic population.
To date, reliable data of chronic exposure to ultrafine particles are still lacking which in turn leads to the fact that no air quality standards are established regarding this air pollution metric. In terms of filling this gap, we examined the association of long-term exposure to air pollution and the inflammatory marker hs-CRP. We focused on ultrafine particles, but also other PM metrics, soot, nitrogen oxides and ozone were of interest. We hypothesized that long-term exposure to ambient air pollution would be positively associated with hs-CRP with ultrafine particles comprising higher toxicity.
Section snippets
Study population
This cross-sectional analysis is part of the KORA (Cooperative Health Research in the Region of Augsburg) study, a population-based, prospective cohort study conducted in southern Germany. Study participants were selected randomly from population registries in the city of Augsburg and two adjacent counties. A total of 4261 participants were examined at baseline (1999–2001) and 2279 of these participants took part in the second follow-up conducted from 2013 to 2014. The latter served as the data
Study population
Characteristics of the study population are presented in Table 1. In total, 2279 subjects participated in the study of which 25 had to be excluded due to missing data in either the outcome (N = 19), the exposure (N = 1) or the covariates (N = 5) of the main model. Two outliers were excluded after the inspection of residual plots and thus 2252 participants remained for our analyses. The study population available for analyses did not show systematic differences regarding outcome, exposure or
Summary
This cross-sectional study conducted in the city and the region of Augsburg in Germany investigated the association between long-term exposure to ultrafine particles and further ambient air pollutants and the inflammatory marker hs-CRP. Although we did not find statistically significant associations the results showed a trend to a positive association for PNC, PM10, PMcoarse, PM2.5abs, NO2 and NOx. No association was seen for PM2.5. The effect estimates were enhanced for females, non‐obese
Conclusion
Single-pollutant models showed a positive yet statistically non-significant association of long-term exposure to ultrafine particles and several other air pollutants with elevated levels of the inflammatory marker hs-CRP but no association for PM2.5 or O3. After adjustment for PM2.5, effect estimates increased for PNC and PM10 and reached significance. Our results highlight the role of ultrafine particles within the complex mixture of ambient air pollution and their inflammatory potential and
Declaration of interest
Nothing to declare.
Acknowledgements
The KORA study was initiated and financed by the Helmholtz Zentrum München - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität as part of LMUinnovative. In addition, this work was supported by intramural funding for Environmental Health projects of Helmholtz
References (49)
- et al.
Development of NO2 and NOx land use regression models for estimating air pollution exposure in 36 study areas in Europe –the ESCAPE project
Atmos. Environ.
(2013) - et al.
Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the global burden of diseases study 2015
Lancet
(2017) - et al.
Association of exposure to particulate matter (PM2.5) air pollution and biomarkers of cardiovascular disease risk in adult NHANES participants (2001–2008)
Int. J. Hyg. Environ. Health
(2016) - et al.
Association of modeled long-term personal exposure to ultrafine particles with inflammatory and coagulation biomarkers
Environ. Int.
(2016) - et al.
Cross-sectional association between exposure to particulate matter and inflammatory markers in the Japanese general population: NIPPON DATA2010
Environ. Pollut.
(2016) - et al.
Chronic PM2.5 exposure and inflammation: determining sensitive subgroups in mid-life women
Environ. Res.
(2014) - et al.
Long-term associations of modeled and self-reported measures of exposure to air pollution and noise at residence on prevalent hypertension and blood pressure
Sci. Total Environ.
(2017) - et al.
Land use regression modeling of ultrafine particles, ozone, nitrogen oxides and markers of particulate matter pollution in Augsburg, Germany
Sci. Total Environ.
(2017) - et al.
Systemic effects of smoking
Chest
(2007) Clinical relevance for lowering C-reactive protein with statins
Ann. Med.
(2016)
Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress
Part Fibre Toxicol.
Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress
Circ. Res.
Atmospheric aerosol measurements in the German Ultrafine Aerosol Network (GUAN) – Part 3: black carbon mass and particle numberconcentrations 2009–2014
Gefahrstoffe – Reinhaltung der Luft.
Particulate matter air pollution and cardiovascular disease. An update to the scientific statement from the American Heart Association
Circulationn
Cardiovascular effects of air pollution
Clin. Sci. (Lond.)
Metabolic syndrome and inflammatory responses to long-term particulate air pollutants
Environ. Health Perspect.
Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health
Environ. Health Perspect.
Diabetes, obesity, and hypertension may enhance associations between air pollution and markers of systemic inflammation
Environ. Health Perspect.
Stability of measured and modelled spatial contrasts in NO(2) over time
Occup. Environ. Med.
Development of land use regression models for PM(2.5), PM(2.5) absorbance, PM(10) and PM(coarse) in 20 European study areas; results of the ESCAPE project
Environ. Sci. Technol.
Chronic exposure to outdoor air pollution and markers of systemic inflammation
Epidemiology (Cambridge, Mass)
Development and back-extrapolation of NO2 land use regression models for historic exposure assessment in Great Britain
Environ. Sci. Technol.
Long-term exposure to air pollution and markers of inflammation, coagulation, and endothelial activation: a repeat-measures analysis in the Multi-Ethnic Study of Atherosclerosis (MESA)
Epidemiology (Cambridge, Mass)
Association between source-specific particulate matter air pollution and hs-CRP: local traffic and industrial emissions
Environ. Health Perspect.
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- 1
The KORA-Study Group consists of A. Peters (speaker), H. Schulz, L. Schwettmann, R. Leidl, M. Heier, K. Strauch, and their co-workers, who are responsible for the design and conduct of the KORA studies.