Fine particulate matter components and interstitial lung disease in rheumatoid arthritis

Abstract

Exposure to ambient fine particulate matter (PM2.5) is a risk factor for pulmonary and systemic autoimmune diseases, however evidence on which PM2.5 chemical components are more harmful is still scant. Our goal is to investigate potential associations between PM2.5 components and interstitial lung disease (ILD) onset in rheumatoid arthritis (RA).New-onset RA subjects identified from a United States health care insurance database (MarketScan) were followed for new onset of RA associated ILD (RA-ILD) from 2011 to 2018. Annual ambient PM2.5 concentrations of its chemical components (i.e. sulfate, nitrate, ammonium, organic matter, black carbon, mineral dust, and sea salt) were estimated by combining satellite retrievals with chemical transport modelling and refined by geographically weighted regression. Exposures from 2006 up to one year before ILD onset or end of study were assigned to subjects based on their metropolitan division or core-based statistical area codes. A novel time-to-event quantile-based g(generalised)-computation approach was used to estimate potential associations between RA-ILD onset and the exposure mixture of all seven PM2.5 chemical components adjusting for age, sex, and prior chronic obstructive pulmonary disease (as a proxy for smoking).We followed 280 516 new-onset RA patients and detected 2194 RA-ILD cases across 1 394 385 person-years. The adjusted hazard ratio for RA-ILD onset was 1.54 (95% confidence interval 1.47–1.63) per every decile increase in all seven exposures. Ammonium, mineral dust, and black carbon contributed more to ILD risk than the other PM2.5 components.In conclusion, exposure to elements of PM2.5, particularly ammonium, increases ILD risk in RA.

Association of Particulate Matter Exposure With Lung Function and Mortality Among Patients With Fibrotic Interstitial Lung Disease

“…Multiconstituent analyses of mortality and baseline lung function outcomes were performed with quantile-based g-computation with a linear additive approach for the addition of each PM 2.5 constituent, as has been previously used with this exposure-matching approach. 31 A random-effects meta-analysis of effect estimates across the 3 cohorts was performed for all primary outcomes, with I 2 values for heterogeneity reported.…”

“…33,34 Recent work also indicates that a higher ammonium level may be associated with increased incidence of ILD among patients with rheumatoid arthritis, also indicating that this constituent may have pathophysiologic relevance to both the development and progression of fILDs. 31 Attributable risk fractions illustrate how the association between PM 2.5 and fILD mortality varies substantially, depending on the mass and constituent makeup of PM 2.5 in a region. An attributable risk fraction can exceed 100% because of complex interactions between social, environmental, and biologic risk factors, indicating the need to interpret these findings with caution, 35 but the Simmons cohort's attributable risk fraction of 0.71 for patients exposed to high PM 2.5 levels (≥8 μg/m 3 ) implies that 71% of this group's premature mortality could have been averted if the exposure had not occurred.…”

Assessment of Risk of Rheumatoid Arthritis Among Underground Hard Rock and Other Mining Industry Workers in Colorado, New Mexico, and Utah

“…It is intriguing that black carbon was found to stimulate protein citrullination in vitro to a degree similar to the effect of silica . Also relevant to this question, recent epidemiologic data suggest that black carbon as a component of fine particulate air pollution may be a risk factor for lung fibrosis in newly diagnosed RA . The duration of employment in underground coal mining, however, was substantially longer than that in hard rock mining in our study population, which could account for the point estimate of higher odds of disease in the former group and the attenuation of risk for the latter, especially when considering the more restrictive, DMARD-based definition of disease.…”

Contemporary Concise Review 2022: Interstitial lung disease

“…Although the highest proportion of exposures were seen in HP, surprisingly they were present in more than a third of IPF, CTD‐ILD and unclassifiable ILD cases, suggesting a role for these exposures across the fILDs. Inhalational exposure to fine particulate matter and occupational exposure to toxicants are associated with ILD risk in rheumatoid arthritis and forced vital capacity (FVC) decline in systemic sclerosis (SSc), respectively 28,29 . It may therefore follow that there are triggers associated with the development of fibrosis in these conditions beyond the known auto‐inflammatory component.…”

“…Inhalational exposure to fine particulate matter and occupational exposure to toxicants are associated with ILD risk in rheumatoid arthritis and forced vital capacity (FVC) decline in systemic sclerosis (SSc), respectively. 28,29 It may therefore follow that there are triggers associated with the development of fibrosis in these conditions beyond the known autoinflammatory component.…”