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      Associations between Ambient Fine Particulate Levels and Disease Activity in Patients with Systemic Lupus Erythematosus (SLE)

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          Abstract

          Background

          Systemic lupus erythematosus (SLE) is a chronic disease of unclear etiology, characterized by an overactive immune system and the production of antibodies that may target normal tissues of many organ systems, including the kidneys. It can arise at any age and occurs mainly in women.

          Objective

          Our aim was to evaluate the potential influence of particulate matter (PM) air pollution on clinical aspects of SLE.

          Methods

          We studied a clinic cohort of SLE patients living on the island of Montreal, followed annually with a structured clinical assessment. We assessed the association between ambient levels of fine PM [median aerodynamic diameter ≤ 2.5 μm (PM 2.5)] measured at fixed-site monitoring stations and SLE disease activity measured with the SLE Disease Activity Index, version 2000 (SLEDAI-2K), which includes anti–double-stranded DNA (anti-dsDNA) serum-specific autoantibodies and renal tubule cellular casts in urine, which reflects serious renal inflammation. We used mixed effects regression models that we adjusted for daily ambient temperatures and ozone levels.

          Results

          We assessed 237 patients (223 women) who together had 1,083 clinic visits from 2000 through 2007 (mean age at time of first visit, 41.2 years). PM 2.5 levels were associated with anti-dsDNA and cellular casts. The crude and adjusted odds ratios (reflecting a 10-μg/m 3 increase in PM 2.5 averaged over the 48 hr prior to clinical assessment) were 1.26 [95% confidence interval (CI), 0.96–1.65] and 1.34 (95% CI, 1.02–1.77) for anti-dsDNA antibodies and 1.43 (95% CI, 1.05–1.95) and 1.28 (0.92–1.80) for cellular casts. The total SLEDAI-2K scores were not associated with PM 2.5 levels.

          Conclusions

          We provide novel data that suggest that short-term variations in air pollution may influence disease activity in established autoimmune rheumatic disease in humans. Our results add weight to concerns that pollution may be an important trigger of inflammation and autoimmunity.

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          Most cited references15

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          Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.

          M Hochberg (1997)
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            Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)).

            Elevated levels of ambient particulate matter (PM(10)) have been associated with increased cardiopulmonary morbidity and mortality. We previously showed that the deposition of particles in the lung induces a systemic inflammatory response that includes stimulation of the bone marrow. This marrow response is related to mediators released by alveolar macrophages (AM) and in this study we measured cytokines produced by human AM exposed to ambient particles of different composition and size. Identified cytokines were also measured in the circulation of healthy young subjects exposed to air pollutants during the 1997 Southeast Asian forest fires. Human AM were incubated with particle suspensions of residual oil fly ash (ROFA), ambient urban particles (EHC 93), inert carbon particles, and latex particles of different sizes (0.1, 1, and 10 microm) and concentrations for 24 h. Tumor necrosis factor-alpha (TNF-alpha) increases in a dose-dependent manner when AM were exposed to EHC 93 particles (p < 0.02). The TNF response of AM exposed to different sizes of latex particles was similar. The latex (158 +/- 31%), inert carbon (179 +/- 32%), and ROFA (216 +/- 34%) particles all show a similar maximum TNF response (percent change from baseline) whereas EHC 93 (1,020 +/- 212%, p < 0.05) showed a greater maximum response that was similar to lipopolysaccharide (LPS) 1 microg/ml (812 +/- 320%). Macrophages incubated with an optimal dose of EHC 93 particles (0.1 mg/ml) also produce a broad spectrum of other proinflammatory cytokines, particularly interleukin (IL)-6 (p < 0.01), IL-1 beta (p < 0.05), macrophage inflammatory protein-1 alpha (MIP-1 alpha) (p < 0.05), and granulocyte macrophage colony-stimulating factor (GM-CSF) (p < 0.01) with no difference in concentrations of the anti-inflammatory cytokine IL-10 (p = NS). Circulating levels of IL-1 beta, IL-6, and GM-CSF were elevated in subjects exposed to high levels of PM(10) during an episode of acute air pollution. These results show that a range of different particles stimulate AM to produce proinflammatory cytokines and these cytokines are also present in the blood of subjects during an episode of acute atmospheric air pollution. We postulate that these cytokines induced a systemic response that has an important role in the pathogenesis of the cardiopulmonary adverse health effects associated with atmospheric pollution.
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              Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers.

              We tested the hypothesis that exposure of healthy volunteers to concentrated ambient particles (CAPS) is associated with an influx of inflammatory cells into the lower respiratory tract. Thirty-eight volunteers were exposed to either filtered air or particles concentrated from the immediate environment of the Environmental Protection Agency (EPA) Human Studies Facility in Chapel Hill, North Carolina. Particle concentrations in the chamber during the exposures ranged from 23.1 to 311.1 microgram/m(3). While in the exposure chamber, volunteers alternated between moderate exercise (15 min) and rest (15 min) for a total exposure time of 2 h. There were no symptoms noted by volunteers after the exposure. Similarly, there were no decrements in pulmonary function. Eighteen hours after exposure, analysis of cells and fluid obtained by bronchoalveolar lavage showed a mild increase in neutrophils in both the bronchial and alveolar fractions in those individuals exposed to CAPS (8.44 +/- 1.99 and 4.20 +/- 1.69%, respectively, in those with the greatest exposure) relative to filtered air (2.69 +/- 0.55 and 0.75 +/- 0.28%, respectively). Blood obtained 18 h after exposure to CAPS contained significantly more fibrinogen relative to samples obtained before exposure. We conclude that ambient air particles are capable of inducing a mild inflammation in the lower respiratory tract, as well as an increased concentration of blood fibrinogen.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                January 2011
                22 September 2010
                : 119
                : 1
                : 45-49
                Affiliations
                [1 ] Division of Clinical Epidemiology and
                [2 ] Division of Rheumatology, McGill University Health Centre, Montreal, Quebec, Canada
                [3 ] Direction de santé publique de l’Agence de la santé et des services sociaux de Montréal, Montreal, Quebec, Canada
                [4 ] Division of Clinical Immunology and Allergy, McGill University Health Centre, Montreal, Quebec, Canada
                [5 ] Département de santé environnementale et de santé au travail, Université de Montréal, Montreal, Quebec, Canada
                [6 ] Institut national de santé publique du Québec, Montréal, Quebec, Canada
                Author notes
                Address correspondence to A. Smargiassi, Institut National de santé publique du Québec/Direction de santé publique de Montréal, 1301 Sherbrooke Est, Montréal, Québec, Canada H2L 1M3. Telephone: (514) 528-2400 ext. 3226. Fax: (514) 528-2459. E-mail: asmargia@ 123456santepub-mtl.qc.ca .

                The authors declare they have no actual or potential competing financial interests.

                Article
                ehp-119-45
                10.1289/ehp.1002123
                3018498
                20870568
                785f35a3-2240-4ca6-a2e7-b294c8bde1ea
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 4 March 2010
                : 22 September 2010
                Categories
                Research

                Public health
                systemic lupus erythematous,sle,antibodies,disease activity,sledai-2k,air pollution,pm2.5
                Public health
                systemic lupus erythematous, sle, antibodies, disease activity, sledai-2k, air pollution, pm2.5

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