PURPOSE: Pulmonary fibrosis is a hallmark of progressive interstitial lung diseases. Previous studies suggested an important role of mediators, such as transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), or ‘Th2’ cytokines (interleukin [IL-]13, IL-4) in the development of this condition. However, few studies have addressed the expression of these mediators within the clinical setting of pulmonary fibrosis. The aim of this retrospective study was to correlate the transcription of TGF-β1, CTGF, IL-4, IL-13, and interferon-gamma (IFN-γ) with lung function development in pulmonary fibrosis.
METHODS: Between 2001 and 2006, we performed 179 sets of PCR-based assessments in 49 patients with UIP, NSIP or pulmonary fibrosis with features of both UIP and NSIP. Specimens were taken by surgical and transbronchial lung biopsy. Lung function was measured at the time of biopsy and after one year. All patients received only conventional treatment. 13 individuals undergoing lung biopsy for diagnosis of radiological lesions were used as control. Statistical analysis was done by Spearman’s test and Mann-Whitney U test.
RESULTS: Transcription of TGF-β1, CTGF and IL-13 was significantly higher in pulmonary fibrosis compared to control, whereas transcription of IFN-γ and IL-4 genes was virtually absent in both normal and fibrotic lungs. When comparing gene transcription and lung function after one year, a significant correlation was observed between TGF-β1 and CTGF and the decrease of pulmonary diffusion capacity, whereas the increase of PaCO2 was only correlated to the transcription of TGF-β1. Decrease of vital capacity and total lung capacity correlated with transcription of TGF-β1 and IL-13. While transcription pattern in transbronchial or surgical samples was similar for all genes tested, gene transcription was generally more intense in transbronchial biopsies. No significant difference in gene transcription was observed between UIP and NSIP.
CONCLUSION: We found a significant correlation between gene transcription levels and decrease of lung function which was more pronounced for TGF-β1 than for CTGF or IL-13.
CLINICAL IMPLICATIONS: Our results suggest that biological assessment can be used for clinical characterization of pulmonary fibrosis.
DISCLOSURE: Marcin Golec, None.