Matrix Metalloproteinase in Idiopathic Pulmonary Fibrosis / 결핵

BACKGROUND: Matrix metalloproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. METHOD: Forty one progressive IPF patients(age 59.82±1.73 years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age: 63.6±2.8 years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography ans the TIMP-1 level was measured by ELISA. RESULTS: 1) The MMP-2 level in BALF was highest in the progressive IPF group (1.36±0.28) followed by the stable group (0.46±0.13) and the controls (0.08±0.09). which was statistically significant. The MMP-9 level of the IPF (0.31±0.058) and the stable group (0.22±0.078) were higher than that of the control group (0.002±0.004). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group (0.80±0.10) than in the control group (0.23±0.081) The MMP-1 level was also higher in both the IPF (36.34±8.62 µg/ml) and stable group (20.83±8.53 µg/ml) compared to the control group (2.80±1.05 µg/ml) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574) (p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils (r=0.449, p=0.059). CONCLUSION: Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

The Clinical Characteristics of Lung Cancer in Patients with Idiopathic Pulmonary Fibrosis / 결핵

BACKGROUND: It has been generally known that the incidence of lung cancer is higher in the patients with idopathic pumonary fibrosis (IPF) than those in general population the reported incidences was variable from 4.8 to 43.2%. There were controversies on the most frequent cell type (squamous cell carcinoma vs. adenocarcinoma) and no study was done about the real concordance of cancer and the fibrotic lesion. And the pulmonary fibrosis may influence not only the development of cancer but also the treatment and prognosis of the cancer, but there was no report on that point. METHOD: Total 63 patients (66.8 ? 7.8 year, M:F=61:2) were diagnosed as IPF combined with lung cancer(IPF-CA) at Asan Medical Center. A retrospective analysis was done about the risk factors of the lung cancer, pulmonary function test, the site of cancer(especially the relationship of the cancer with the fibrotic lesion), the histologic types, and the stage of cancer. The histologic types were compared with these of 2,660 patients with lung cancer who were diagnosed at the same institute for the same period. The effect of IPF on the treatment of the cancer was evaluated with the survival time after the detection of lung cancer. RESULTS: The lung cancer was found in 63(22.9%) out of 281 patients with IPF. But in most of them(45 patients), lung cancer was detected at the same time with IPF and only in 18 patients, the cancer was diagnosed during the follow-up (25.2+/-17.7 months) of IPF. So in our study, 6.7% of patients with IPF developed lung cancer during the course of the disease. The age (66.8+/-7.84 vs. 63.4+/-11.1 years), percentage of smoker (88.9 vs. 67.2%), and the male gender (96.8 vs. 67.6%) were significantly higher in IPF-CA compared with lone IPF (p<0.05). The odds ratio of smoking was 4.7 compared with non smoking IPF controls. The lung cancer was located more frequently in the upper lobe and 55.5% was in the periphery of lung. The cancer was developed in the fibrotic lesion in 23 patients (35.9%), and in the majority of the patients, the cancer was separated from the fibrosis. The cell type of the lung cancer in IPF-CA was squamous cell carcinoma 34.9%, adenocarcinoma 30.2%, small cell carcinoma 19.0%, large cell undifferenciated carcinoma 6.3%, and others 9.5%. No significant difference in the distribution of histologic type of the lung cancer was found between IPF-CA and lone lung cancer. There was no significant difference in demographic features, cell types, location and the stage of the cancer between the group with concurrent IPF-CA and the group with cancer diagnosed during the follow up of IPF. There was a tendency (but statistically not significant : p=0.081) of higher incidence of adenocarcinoma among the cancers developed in the fibrotic area (43.5%) (F-CA) than in the cancers in non-fibrotic area (22.5%) (NF-CA). The prognosis of the patients with F-CA was poor (median survival : 4 months) compared with the patients with NF-CA (7 months, p=0.013), partly because the prevalence of severe IPF (the extent of fibrosis in HRCT ?50%) was higher in F-CA group. CONCLUSION: These data suggest that the lung cancer in the patients with IPF has similar features to the ordinary lung cancer.