Characterization of lung function impairment and pathological changes induced by chronic lead and cadmium inhalation: Insights from a mouse model study.

Exposure to environmental heavy metals such as lead (Pb) and cadmium (Cd) is a global concern due to their widespread presence. However, the specific pulmonary effects of inhaled exposure, especially related to long-term effects, remain poorly understood. In this study, we developed a novel mouse model of Pb and Cd inhalation to mimic real-world conditions and investigate pulmonary effects. Mice were exposed to Pb and Cd inhalation for 6 months using a whole-body exposure system, resulting in decreased lung compliance and progression from emphysematous changes to fibrosis. In addition, the blood Pb/Cd levels of mice exposed to Pb/Cd for 6 months are like those of humans occupationally exposed to heavy metals. Histology revealed inflammation and collagen deposition. Transcriptomic analysis highlighted immune responses and macrophage activity in developing fibrosis. These results confirm an association between Pb/Cd exposure and emphysema and fibrosis, reflecting clinical findings. The study highlights the importance of long-term exposure assessment and time-course analysis for understanding Pb/Cd-induced lung disease. The relevance of the mouse model in replicating human exposure scenarios underscores its value in studying fibrosis and emphysema simultaneously. These findings provide a basis for targeted therapeutic interventions against heavy metal-induced lung injury.