Occupational exposures raise risk of pulmonary sarcoidosis: Study
More than 80 airborne factors linked to disease were found in dozens of studies
Workplace exposure to silica, mold/mildew, and pesticides were associated with an increased risk of pulmonary sarcoidosis in a recent review study.
By analyzing data from dozens of published studies, scientists identified more than 80 different airborne factors that have been linked to the disease in at least one study.
“It is highly unlikely a single [airborne factor] is responsible for the onset of sarcoidosis—the onset is far more likely the result of a complex genetic–environment–immunological interaction,” the researchers wrote.
Scientists believe the findings offer new avenues for further investigating how pulmonary sarcoidosis arises.
The study, “Airborne occupational exposures associated with pulmonary sarcoidosis: a systematic review and meta-analysis,” was published in Occupational & Environmental Medicine.
Airborne exposures could contribute to pulmonary sarcoidosis
It is not exactly known how sarcoidosis occurs. However, it has been proposed that exaggerated and prolonged immune responses to environmental exposures drives the formation of granulomas — the clumps of inflammatory cells that characterize the disease — particularly in people who may be genetically predisposed.
Airborne exposures, or particles suspended in the air that can be inhaled into the respiratory tract, could be particular contributors to pulmonary sarcoidosis, where granulomas form in the lungs.
Previous research showed certain occupational groups, including firefighters, nurses, and military personnel, are at a higher risk of sarcoidosis, suggesting occupational exposures may play an important role in driving the disease.
Indeed, occupational exposure to metal dust, pesticides, and silica — the most abundant mineral in Earth’s crust — have been associated with sarcoidosis risk.
To learn more about the possible contributions of airborne occupational exposures to pulmonary sarcoidosis, a team of researchers in the U.K. systematically reviewed studies on the topic published between January 1958 and December 2022.
Eligible studies included only adults and where specific occupational exposures were confirmed to have occurred prior to the sarcoidosis diagnosis.
Across 76 studies — including retrospective studies, longitudinal studies following certain groups of people over time, case reports, and case series — 81 different airborne occupational exposures had been linked to pulmonary sarcoidosis.
These exposures could be broadly categorized into six groups: mineral dusts (e.g., silica), mixed dusts/fumes, organic dusts (e.g., mold or mildew), metals, chemicals (e.g., pesticides), and radiation.
Silica exposure reported in 33 studies
The exposure most commonly associated with pulmonary sarcoidosis was silica, reported in 33 studies. Given its abundance and the prevalent breakdown of minerals in industry, silica exposure is common in occupations such as iron foundry, construction work, and mining. In addition to sarcoidosis, silica previously has been linked to autoimmune inflammatory conditions.
Data from 12 retrospective and longitudinal studies were included in a meta-analysis meant to assess the pulmonary sarcoidosis risk associated with occupational exposures.
The analysis indicated that silica exposure was significantly linked to a 26% higher risk of pulmonary sarcoidosis, mold/mildew exposure to a 52% greater risk, and pesticide exposure to a 42% higher risk.
Occupational exposure to metals, including nickel and aluminum, also was associated with an increase in disease risk, but these links did not reach statistical significance. Therefore, their relationship with sarcoidosis remains less clear.
Exposure to other particles were significantly associated with an increased risk of pulmonary sarcoidosis in a single retrospective study. The one showing the strongest link was the titanium metal, being linked to a threefold higher risk.
It was followed by photocopier toner and organic dust, which were associated with a more than twice higher risk, and radiation and vegetable dust that were linked to a risk that was increased by about 80%.
The researchers also analyzed data from 26 studies reporting on the mineral content of granulomas from pulmonary sarcoidosis patients. A wide range of substances were identified, including silica, nickel, aluminum, and titanium, “with some studies identifying the presence of multiple elements in the same granuloma,” the team wrote.
These elements “might be responsible for stimulating [immune] responses seen in granulomas,” the researchers added.
Overall, “the large number of airborne occupational exposures associated with a diagnosis of pulmonary sarcoidosis … suggest it is highly probable that there is no single environmental exposure trigger,” the team wrote. “Instead, one could hypothesise that various exposures trigger a common inflammatory pathway stimulating a granulomatous response.”
The scientists noted some exposures, including silica, could lead to immune responses that look similar to sarcoidosis, but are different. Given that fact, “an environmental and occupational exposure history is important in the workup of sarcoidosis,” the team wrote.
While the exact immune mechanisms underlying the potential link between airborne exposures and pulmonary sarcoidosis are “beyond the scope of this review,” the scientists offered some speculations.
For example, silica may lead to the generation of antibodies against certain protein fragments that drive prolonged production of inflammatory molecules. In turn, organic dusts like mold and mildew could drive immune responses because they often contain bacteria, fungi, or other microbes that the immune system responds to.
Pesticides have long been associated with a risk of a number of different diseases. Chemicals like these are known to be able to induce cellular damage that drives inflammation.
Overall, “while this review identifies the role of specific occupational exposures in the onset of sarcoidosis, it also generates further questions,” the researchers wrote.
For example, more work will be needed to understand how genetic factors might interact with these environmental ones in sarcoidosis, and how the mineral composition in granulomas might influence immune activity.
“Future studies should examine the potentially complex relationship between genetic factors and airborne occupational exposures and the mineralogical composition of sarcoidosis granulomas,” the team concluded.
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