You are here:
The Role of Particle Inhalation in Idiopathic Pulmonary Fibrosis
Citation:
Ghio, A., R. Sangani, AND N. Todd. The Role of Particle Inhalation in Idiopathic Pulmonary Fibrosis. International Journal of Molecular Sciences. MDPI, Basel, Switzerland, 26(17):8736, (2025). https://doi.org/10.3390/ijms26178736
Impact/Purpose:
This manuscript provides a pathway or pathogenesis for idiopathic pulmonary fibrosis following particle exposure. This is attributable to particle causing a functional iron deficiency and the host responding with fibrosis in an effort to correct metal homeostasis.
Description:
Abstract Idiopathic pulmonary fibrosis (IPF) is considered a distinctive type of progressive, fibrosing interstitial pneumonitis associated with either 1) a histopathologic or 2) a radiologic pattern of usual interstitial pneumonia (UIP). The diagnosis of IPF requires that other interstitial lung diseases (ILDs) be excluded. Such exclusion is impossible without methodology which can require significant expense and therefore of limited availability. As a result of a lack of a recognized etiology and pathogenesis, diagnosing IPF is challenging and misdiagnosis is common. Rather than being idiopathic, it is proposed that almost all cases of IPF result from particle and fiber (particle/fiber) exposure. Cigarette smoking presents the greatest particle/fiber challenge in any society and demonstrates a relationship with numerous fibrotic interstitial lung diseases including IPF. Environmental exposures to particle/fiber other than cigarette smoking, including biomass fuel smoke and ambient air pollution, have also been associated with IPF. Finally, occupational particle/fiber exposures have similarly accounted for numerous cases of IPF. In the pathogenesis of IPF, particle/fiber exposures function to impact iron homeostasis and result in a cell deficiency of the metal. Associated with decreased iron availability, a synthesis of biopolymers included in extracellular matrix results. The biopolymers complex metal and, with depolymerization, provide iron to cells via receptor mediated uptake which subsequently reverses the deficiency. Rather than being an aberrant process, pulmonary fibrosis following pulmonary/fiber exposure can be an appropriate and advantageous response to functional iron deficiency.
