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The Role of Particle Inhalation in Idiopathic Pulmonary Fibrosis
Andrew J Ghio1, Rahul G Sangani2, Nevins W Todd3
1US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
International Journal of Molecular Sciences
|September 13, 2025
Summary
Idiopathic pulmonary fibrosis (IPF) is linked to particle exposure, including smoking and pollution. The disease involves iron dysregulation within lung cells, triggering a fibrotic response.
Area of Science:
- Pulmonary Medicine
- Toxicology
- Cell Biology
Background:
- Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD).
- A histopathologic and radiologic pattern of usual interstitial pneumonia (UIP) defines IPF.
- Numerous studies link IPF diagnoses to particle exposures.
Purpose of the Study:
- To describe the relationship between IPF and particle exposure.
- To propose a pathogenesis for IPF based on particle exposure.
- To explain the role of iron dysregulation in IPF development.
Main Methods:
- Review of clinical studies and epidemiological investigations.
- Analysis of environmental and occupational particle exposures.
- Description of cellular mechanisms involving iron sequestration and biopolymer synthesis.
Main Results:
- Cigarette smoking, biomass fuel smoke, air pollution, and occupational exposures are associated with IPF.
- Particle exposure leads to iron sequestration and functional intracellular iron deficiency.
- Biopolymers like hyaluronic acid are synthesized, complex iron, and facilitate intracellular delivery, reversing deficiency.
Conclusions:
- Pulmonary fibrosis in IPF is a response to altered intracellular iron metabolism caused by particle exposure.
- The heterogeneity of IPF reflects a dose-response relationship with retained particles and fibrosis reversibility.
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