Minute lesions of alveolar damage in lungs of patients with stable idiopathic pulmonary fibrosis.
AIMS
To investigate the mechanisms underlying the acute exacerbation of idiopathic pulmonary fibrosis, and in particular the role of minute lesions of alveolar damage.


METHODS AND 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.
['Emura|Iwao|I|', 'Usuda|Hiroyuki|H|', 'Togashi|Kenichi|K|', 'Satou|Kazuhiro|K|']
D000368:Aged D051792:Basic Helix-Loop-Helix Transcription Factors D001706:Biopsy D005260:Female D006801:Humans D054990:Idiopathic Pulmonary Fibrosis D008264:Macrophages D008297:Male D008875:Middle Aged D009504:Neutrophils D011650:Pulmonary Alveoli D014409:Tumor Necrosis Factor-alpha
minute lesion of alveolar damage idiopathic pulmonary fibrosis acute exacerbation macrophage neutrophil hypoxia-inducible factor-2α tumour necrosis factor-α