Proliferative activity in fibrosing lung diseases: a comparative study of Ki-67 immunoreactivity in diffuse alveolar damage, bronchiolitis obliterans-organizing pneumonia, and usual interstitial pneumonia

Hum Pathol. 2009 Aug;40(8):1182-8. doi: 10.1016/j.humpath.2009.01.006. Epub 2009 Apr 14.


Because diffuse alveolar damage, bronchiolitis obliterans-organizing pneumonia, and usual interstitial pneumonia are all related to acute lung injury, we postulated that the proliferative activity of fibroblasts and epithelium would be similar in all 3, and that of fibroblasts would be similar to skin scars. Ki-67 staining was assessed in 16 usual interstitial pneumonia, 9 bronchiolitis obliterans-organizing pneumonia, and 8 diffuse alveolar damage cases, 5 incidental fibroblast foci, 5 skin scars, and 5 keloids. The proliferative activity of alveolar macrophages was also measured and compared with that of 10 respiratory bronchiolitis cases. The greatest proliferative activity was found in fibroblasts and epithelium of diffuse alveolar damage (25.8% and 41.9%), and it was significantly greater (P = .000) than in usual interstitial pneumonia (1.88% and 2.6%), bronchiolitis obliterans-organizing pneumonia (4.07% and 1.55%), and incidental fibroblast foci (2.9% and 0.44%). The proliferative activity in fibroblasts of diffuse alveolar damage was significantly higher than that of fibroblasts in skin scars (P = .024). In contrast, the proliferative rate of fibroblasts in bronchiolitis obliterans-organizing pneumonia, usual interstitial pneumonia, and incidental fibroblast foci was significantly lower than that in skin scars (P = .000, P = .000, and P = .001) but similar to keloids (P = 1.000). Usual interstitial pneumonia macrophages showed an unexpectedly high proliferative rate (19.5%) that was significantly greater than that in bronchiolitis obliterans-organizing pneumonia (5.5%, P = .000), diffuse alveolar damage (9.01%, P = .007), incidental fibroblast foci (9.5%, P = .036), and respiratory bronchiolitis (11.45%, P = .031). Our results suggest different reactions to acute injury in usual interstitial pneumonia and bronchiolitis obliterans-organizing pneumonia compared with diffuse alveolar damage. The similar low proliferative activity of fibroblasts in usual interstitial pneumonia and keloids supports the hypothesis of abnormal wound healing in usual interstitial pneumonia. The high proliferative activity of macrophages in usual interstitial pneumonia suggests a role in the pathogenesis of usual interstitial pneumonia.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Cell Count
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Cryptogenic Organizing Pneumonia / metabolism*
  • Cryptogenic Organizing Pneumonia / pathology
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Keloid / metabolism
  • Keloid / pathology
  • Ki-67 Antigen / metabolism*
  • Lung Diseases, Interstitial / metabolism*
  • Lung Diseases, Interstitial / pathology
  • Male
  • Middle Aged
  • Pulmonary Alveoli / metabolism*
  • Pulmonary Alveoli / pathology
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • Young Adult


  • Biomarkers
  • Ki-67 Antigen