Repeated diesel particle exposure triggers hypersensitivity pneumonitis-like response, study finds

Repeated exposure to fine particles emitted by diesel engines can go beyond simple lung inflammation and affect the immune system in ways that resemble hypersensitivity pneumonitis, according to new research.

The Korea Institute of Toxicology (KIT) said researchers Yang Hyo-seon and Lee Ji-han of its Respiratory Safety Research Center confirmed immune and pathological changes similar to hypersensitivity pneumonitis in an animal model subjected to repeated exposure to diesel engine exhaust particles.

Hypersensitivity pneumonitis is a condition in which repeated exposure to specific antigens triggers an immune response in the lungs. While it has long been known that diesel exhaust particles can cause pulmonary inflammation and immune toxicity, experimental evidence directly demonstrating that such exposure could lead to immunopathological changes resembling hypersensitivity pneumonitis had been insufficient.

The researchers administered diesel exhaust particles into the airways of mice once a day for 14 days, then analyzed pulmonary immune responses and tissue changes.

As a result, lymphocytes — immune cells — increased in bronchoalveolar lavage fluid, which reflects the internal state of the lungs. Lung tissue showed pathological changes similar to hypersensitivity pneumonitis, including mononuclear cell infiltration and the formation of "non-caseating granulomas." Granulomas are clusters of immune cells that form in response to foreign substances that are difficult to eliminate.

The researchers also found similarities with human patients. When they compared gene expression in the lung tissue of repeatedly exposed mice with that of patients with chronic hypersensitivity pneumonitis, shared characteristics emerged in some genes associated with immune responses to foreign substances.

Based on these findings, the researchers proposed a "putative adverse outcome pathway," or pAOP, describing the sequence from repeated diesel particle exposure through pulmonary inflammation, macrophage activation, and antigen processing and immune activation, culminating in pathological changes resembling hypersensitivity pneumonitis.

The study is particularly significant because it went beyond confirming a link between air pollution particles and hypersensitivity pneumonitis in animal experiments, also analyzing histopathological changes, immune mechanisms, and similarities with gene expression patterns observed in actual patients.

However, because the study confirmed only a response "similar to" hypersensitivity pneumonitis in animals, it does not mean diesel particles directly cause hypersensitivity pneumonitis in humans. The researchers said they expect the findings to serve as foundational data for evaluating the immune toxicity and health effects of particulate air pollutants.

"Diesel engine exhaust particles need to be examined not only for their role in transient lung inflammation but also for their immunological effects from repeated exposure," Yang Hyo-seon said. "We hope this research will serve as a scientific basis for assessing the impact of air pollutants on lung health."

The findings were published in the Sept. 15 issue of the international journal Environmental Research.