title: Minute lesions of alveolar damage in lungs of patients with stable idiopathic pulmonary fibrosis.
abstract: OBJECTIVE
  To investigate the mechanisms underlying the acute exacerbation of idiopathic pulmonary fibrosis, and in particular the role of minute lesions of alveolar damage.
  
  
  RESULTS
  We examined surgical lung biopsy samples from 38 patients with stable idiopathic pulmonary fibrosis, and evaluated the association between the foci and development of acute exacerbation. Mild extravasation, probably resulting from lung injury and intra-alveolar oedema fluid, were observed in narrow areas of architecturally intact lung tissue. Minute lesions of alveolar damage were detected in these areas. Alveolar epithelial cells in these lesions were injured. Hypoxia-inducible factor-2α-positive macrophages, tumour necrosis factor-α-positive macrophages and neutrophils had accumulated in alveolar spaces in and around these lesions. Cases were classified into patients without (17) and with (21) minute lesions of alveolar damage. Development to acute exacerbation (five cases) occurred only in patients with minute lesions of alveolar damage (P = 0.03).
  
  
  CONCLUSIONS
  The formation of minute lesions of alveolar damage may be initiated by hypoxia, and such lesions play important roles in the development of acute exacerbation.
authors.affiliation: Department of Surgical Pathology, Japanese Red Cross Nagaoka Hospital, Nagaoka City, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Emura
authors.affiliation: Department of Surgical Pathology, Japanese Red Cross Nagaoka Hospital, Nagaoka City, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Usuda
authors.affiliation: Department of General Thoracic Surgery, Japanese Red Cross Nagaoka Hospital, Nagaoka City, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Togashi
authors.affiliation: Department of Internal Medicine, Japanese Red Cross Nagaoka Hospital, Nagaoka City, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Satou
mesh_terms: D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001706:Biopsy; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011650:Pulmonary Alveoli / Q000293:injuries*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014409:Tumor Necrosis Factor-alpha; D000099162:Endothelial PAS Domain-Containing Protein 1
keywords: acute exacerbation; hypoxia-inducible factor-2α; idiopathic pulmonary fibrosis; macrophage; minute lesion of alveolar damage; neutrophil; tumour necrosis factor-α