API

Relationship: 1838

Title

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Airway epithelial injury leads to Increase, Inflammation

Upstream event

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Airway epithelial injury

Downstream event

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Increase, Inflammation

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
α-diketone-induced bronchiolitis obliterans adjacent Not Specified Not Specified

Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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Key Event Relationship Description

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Damage of the airway epithelium leads to inflammatory reactions.

Evidence Supporting this KER

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Biological Plausibility

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Inflammation is a biological response to harmful stimuli, including cell damage. Therefore, damage to airway epithelium will initiate inflammatory reactions.

Empirical Evidence

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Moderately damaged epithelium can regenerate itself after exposure cessation and the inflammatory reaction, initiated by the release of various inflammatory cytokines (Anderson et al. 2010), will be of limited duration. However, severely damaged epithelium is unable to recover, probably due to the depletion of progenitor cells required to regenerate the epithelium (McGraw et al. 2017). This leads to sustained inflammation. The inability of epithelium regeneration and the resulting chronic inflammation might explain the threshold for the manifestation of negative health effects typically observed after α-diketone inhalation.

Uncertainties and Inconsistencies

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It is clear that inflammatory reactions occur after exposure to α-diketones. The exact role of inflammation in the ultimate development of bronchiolitis obliterans remains unclear.

Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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Anderson, S.E., Jackson, L.G., Franko, J., Wells, J.R., 2010. Evaluation of dicarbonyls generated in a simulated indoor air environment using an in vitro exposure system. Toxicol. Sci. 115, 453–461.

McGraw, M. D., Rioux, J. S., Garlick, R. B., Rancourt, R. C., White, C. W., & Veress, L. A. (2017). Impaired proliferation and differentiation of the conducting airway epithelium associated with bronchiolitis obliterans after sulfur mustard inhalation injury in rats. Toxicological Sciences, 157(2), 399–409. https://doi.org/10.1093/toxsci/kfx057