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Fibroproliferative airway lesions leads to Bronchiolitis obliterans
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Excessive proliferation of fibrotic cells and the deposition of extracellular matrix leads to the occlusion of the lumen of the smaller airways.
The occlusion of the lumen of the smaller airways (the bronchioles) results in dry cough, wheezing, shortness of breath and a strongly reduced lung function, the symptoms of bronchiolitis obliterans.
Evidence Supporting this KER
Uncontrolled proliferation of myofibroblast in the airway regions suffering from damaged epithelium and the deposition of extracellular matrix leads to narrowing of the airway lumen or even the complete occlusion of the bronchioles.
Occlusion of the smaller airways blocks the flow of air into and out of the lungs. This leads to a reduced gas exchange and a compromised lung function.
Uncertainties and Inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Morgan, D. L., Jokinen, M. P., Johnson, C. L., Price, H. C., Gwinn, W. M., Bousquet, R. W., & Flake, G. P. (2016). Chemical Reactivity and Respiratory Toxicity of the alpha-Diketone Flavoring Agents: 2,3-Butanedione, 2,3-Pentanedione, and 2,3-Hexanedione. Toxicologic Pathology, 44(5), 763–783. https://doi.org/10.1177/0192623316638962
Rose, C. S. (2017). Early detection, clinical diagnosis, and management of lung disease from exposure to diacetyl. Toxicology, 388, 9–14. https://doi.org/10.1016/j.tox.2017.03.019