# Silent invaders: the role of MPs on epithelium inflammation and damage in airway diseases

## TL;DR

This paper reviews how inhaled microplastics and nanoplastics can damage airway epithelium and contribute to respiratory diseases like asthma, COPD, and lung cancer.

## Contribution

The paper provides a mechanistic review of how microplastics interact with airway epithelium and exacerbate respiratory diseases.

## Key findings

- Microplastics trigger oxidative stress and inflammatory pathways in airway epithelium.
- Smaller particles cause mitochondrial dysfunction and epithelial-mesenchymal transition.
- Microplastics may contribute to lung carcinogenesis through chronic inflammation and oxidative stress.

## Abstract

Microplastics (MPs) and Nanoplastics (NPs) have emerged as pervasive environmental contaminants with growing implications for respiratory health. Increasing evidence demonstrates that inhaled MPs can deposit throughout the airways, interact with epithelial surfaces, and trigger a cascade of inflammatory, oxidative, and structural alterations that may contribute to the onset or progression of airway diseases. Their pathogenicity is influenced by physicochemical properties, including size, shape, density, and surface charge, which determine their aerodynamic behavior, epithelial penetration, and cellular uptake. Once deposited, MPs are associated with epithelial stress responses, including oxidative stress, activation of inflammatory signaling pathways, and alterations in junction-related proteins, which may impair mucociliary function. Smaller particles and NPs are internalized through endocytosis, leading to mitochondrial dysfunction, reactive oxygen species (ROS) generation, and activation of key inflammatory pathways such as NF-κB, PI3K/Akt/mTOR, and Wnt/β-catenin. These mechanisms promote cytokine release, epithelial–mesenchymal transition, and dysregulated repair responses. Experimental and clinical evidence indicate that MPs exacerbate epithelial fragility in asthma and COPD by amplifying oxidative stress, enhancing barrier dysfunction, and intensifying maladaptive crosstalk between epithelial and immune cells. In fibrotic pathways, persistent epithelial injury activates the NLRP3 inflammasome and drives TGF-β1-mediated fibroblast activation and extracellular matrix deposition, establishing a self-perpetuating cycle of inflammation and remodeling. Emerging data suggest a potential role for MPs in lung carcinogenesis through chronic inflammation, indirect genotoxic effects mediated by oxidative stress, and altered cellular homeostasis. Overall, MPs represent an underrecognized but increasingly relevant environmental factor capable of inducing epithelial damage, promoting chronic airway inflammation, and contributing to the pathophysiology of asthma, COPD, pulmonary fibrosis, and possibly lung cancer. Understanding these mechanisms is crucial to guide preventive strategies, regulatory policies, and future clinical research. This review critically evaluates current experimental evidence on microplastic–epithelium interactions, highlighting mechanistic insights, methodological limitations, and key gaps that must be addressed to clarify their role in airway diseases.