title: Pathology of diacetyl and 2,3-pentanedione airway lesions in a rat model of obliterative bronchiolitis.
abstract: Inhalation of diacetyl vapors by workers has been associated with obliterative bronchiolitis (OB), a poorly understood fibroproliferative disease of the small airways. Significant insights into the pathogenesis of OB have been obtained through the use of a rat model. Inhalation exposure of rats to diacetyl or 2,3-pentanedione, a related flavoring agent, can cause severe injury to the airway epithelium and underlying basement membrane. Repeated exposure to diacetyl or 2,3-pentanedione leads to aberrant repair, fibroproliferation and partial to complete occlusion of the airway lumen. Fibroproliferative lesions in rat airways were found to include both intraluminal polyps and circumferential intramural lesions. Intraluminal polyps have been observed to form secondary attachments spanning the airway lumen causing increasing obstruction. These airway lesions in rats are accompanied by inflammation in the form of peribronchial and perivascular infiltrates of lymphocytes, eosinophils and neutrophils. Diacetyl-induced OB lesions in the rat are similar to OB lesions in humans and provide a good model for studying the pathogenesis of this disease.
authors.affiliation: Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, United States.
authors.forename: Gordon P
authors.initials: GP
authors.lastname: Flake
authors.affiliation: Toxicology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, United States. Electronic address: morgan3@niehs.nih.gov.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Morgan
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D001989:Bronchiolitis Obliterans / Q000139:chemically induced* / Q000473:pathology; D003931:Diacetyl / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D005421:Flavoring Agents / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects; D010422:Pentanones / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology; D013045:Species Specificity
chemical_list: D005421:Flavoring Agents; D010422:Pentanones; D003931:Diacetyl; C013186:2,3-pentanedione
keywords: 2,3-Pentanedione; Diacetyl; Histopathology; Obliterative bronchiolitis; Pathogenesis