Airway wall remodeling induced by occupational mineral dusts and air pollutant particles

Our plain-English summary of Airway wall remodeling induced by occupational mineral dusts and air pollutant particles, by A. Churg, J.L. Wright (Chest, 2002).

The study

• Authors: A. Churg, J.L. Wright
• Journal: Chest
• Published: 2002;122(6 Suppl):306S-309S
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: COPD has been reported in workers exposed to particulates, and there is increasing evidence that high levels of ambient particulate pollutants may also be associated with COPD. The studies here investigate the hypothesis that particulates, including air pollution particles, can induce airway wall fibrosis, a process that can lead to COPD.

Design: Rat tracheal explants were exposed to various occupationally encountered dusts, air pollution particles, and model air pollution particles. In some experiments, iron was loaded onto the particle surface. Gene expression and nuclear factor (NF)-kappaB activation were measured after 7 days of air culture. Adhesion to and uptake of dusts by the tracheal epithelium were also evaluated.

Results: Known fibrogenic dusts such as amosite asbestos produced increased gene expression of procollagen, transforming growth factor-beta, and platelet-derived growth factor, and increased hydroxyproline in the explants, and the addition of iron increased these effects. The addition of iron also converted nonfibrogenic TiO2 into a fibrogenic dust. Dusts with surface complexed iron activated NF-kappaB via an oxidant mechanism. However, an ultrafine TiO2 with very low iron was also fibrogenic. In separate experiments, exogenous tumor necrosis factor-alpha increased dust adhesion to, and exogenous ozone increased dust uptake by, tracheal epithelial cells.

Conclusions: Mineral dusts can directly induce fibrosis in the airway wall. Exogenous inflammatory cells and exogenous agents are not required, but they probably exaggerate the fibrogenic effects. An iron-mediated oxidant mechanism underlies the fibrogenic effects of some, but not all, of these dusts. Particle-induced airway wall fibrosis may lead to COPD.

In plain English

This article was a review in which the authors described experiments from their own laboratory. It did not report a single new study. The experiments used small pieces of rat windpipe (tracheal explants) kept alive in culture for up to 7 days and exposed to mineral dusts and air pollution particles. Amosite asbestos increased gene activity for type I procollagen, a building block of collagen. Figure legends state that asbestos alone doubled this activity and produced a small increase in hydroxyproline, a marker of collagen content. Loading extra iron onto the amosite increased these effects. Chemicals that block oxidants or iron prevented the iron-driven increase. Adding iron to titanium dioxide, normally not scar-forming, also raised collagen markers. Ultrafine titanium dioxide, but not fine, increased procollagen gene activity in a dose-response fashion over 7 days. Brief prior exposure to cigarette smoke or ozone increased dust uptake, and the inflammatory signal TNF-alpha increased dust sticking to the airway surface. The authors concluded that mineral dusts and pollution particles can induce airway wall remodeling and thus presumably COPD. They noted that their model used large airways but very likely applies to small airways.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of the authors' own laboratory experiments using a rat tracheal explant (organ culture) model; figures reprinted from their earlier papers
• Who was studied: Two-millimeter rat tracheal explants maintained in air organ culture (up to 7 days); numbers of explants not given in this article
• Exposure: Amosite asbestos, with and without added surface iron; fine (0.12 micrometer) and ultrafine (0.021 micrometer) titanium dioxide, with and without added iron; Ottawa urban air particles and residual oil fly ash; pretreatment with cigarette smoke, ozone (as low as 0.1 ppm) or TNF-alpha (5 and 20 ng/mL)
• Main results:
  • In rat tracheal explants, amosite asbestos alone doubled type I procollagen gene expression, and increasing iron loading increased this effect
  • Amosite asbestos alone produced a small increase in explant hydroxyproline (collagen content), which iron augmented
  • The iron-mediated increases in procollagen were prevented by an oxidant scavenger (tetramethylthiourea) and an iron chelator (deferoxamine)
  • Adding iron to fine titanium dioxide, an ordinarily nonfibrogenic particle, increased procollagen gene expression and hydroxyproline
  • Fine titanium dioxide was not fibrogenic; ultrafine titanium dioxide increased procollagen gene expression in a dose-response fashion over 7 days
  • Brief prior exposure of explants to cigarette smoke or ozone increased dust uptake
  • Pretreatment with TNF-alpha increased adhesion of dust particles, including air pollution particles, to the explant surface
• The authors' conclusion: The authors concluded that mineral dusts and air pollution particles can induce airway wall remodeling and thus presumably COPD
• Limitations the authors state:
  • The model used large airways (trachea) rather than the small airways where obstruction occurs, though the authors considered it very likely applicable

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite.

Medical terms in this study, explained in our Lexicon: COPD, Fibrosis, Epithelium, Fibrogenic, Amosite, Transforming Growth Factor-beta (TGF-β), Platelet-Derived Growth Factor (PDGF), Tumor Necrosis Factor-alpha (TNF-α).

Related studies

• Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall — J. Dai, B. Gilks, et al. (1998)
• Relationship of fiber surface iron and active oxygen species to expression of procollagen, PDGF-A, and TGF-beta(1) in tracheal explants exposed to amosite asbestos — J. Dai, A. Churg (2001)
• Iron enhances uptake of mineral particles and increases lipid peroxidation in tracheal epithelial cells — B. Keeling, K.Y. Li, et al. (1994)
• A new technique to examine individual pollutant particle and fibre deposition and transit behaviour in live mouse trachea — M. Donnelley, K.K. Siu, et al. (2010)
• Effects of cigarette smoke on epithelial uptake of non-asbestos mineral particles in tracheal organ culture — B. Keeling, J. Hobson, et al. (1993)
• Ozone enhances the uptake of mineral particles by tracheobronchial epithelial cells in organ culture — A. Churg, M. Brauer, et al. (1996)

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