Lung Function Changes and Connective Tissue Growth Factor Expression in Idiopathic Pulmonary Fibrosis, Other Progressive Fibrosing Interstitial Lung Diseases, and Post-COVID Fibrosis

Abstract

Background The clinical course of patients with idiopathic pulmonary fibrosis (IPF) and other progressive interstitial lung diseases (F-ILDs) varies from mild to severe worsening, which makes the development of new diagnostic and prognostic methods even more urgent. A number of studies have shown that plasma connective tissue growth factor (CTGF) is elevated during IPF, and that the levels of this substance are correlated with the changes in forced vital capacity (FVC). The aim of our study was to investigate CTGF levels in patients with F-ILDs group, including its subgroups IPF and other F-ILDs, as well as post-COVID-19 cases, and to assess their association with lung function changes over a 12-month period. Methods A prospective cohort study was conducted with patients observed over 30 months. The involvement period was 18 months, followed by a 12-month observation period. A total of 86 subjects were enrolled in the study. FVC (measured by spirometry), diffusing lung capacity for carbon monoxide (DLCO), and CTGF levels in blood serum (measured by enzyme-linked immunosorbent assay (ELISA)) were assessed at the beginning and end of the study. Results Regression analysis of the correlations between mean serum CTGF levels, FVC, and DLCO changes in the F-ILDs group demonstrated a significant negative correlation between the changes in mean serum CTGF levels, FVC, and DLCO. Similarly, in the IPF, idiopathic nonspecific interstitial pneumonia (iNSIP) and chronic sarcoidosis (IV stage) subgroups, there was a significant negative correlation between changes in mean serum CTGF levels, FVC, and DLCO. However, in the post-COVID-19 group, regression analysis did not reveal any correlations between changes in mean serum CTGF concentrations, FVC, and DLCO. Conclusion Our data suggest a correlation between decreased pulmonary function and increased CTGF levels in patients with IPF and other PPF conditions. Therefore, CTGF emerges as a potential surrogate marker for fibrosis progression in these patients. In contrast, post-COVID-19 fibrosis appears to be a non-progressive fibrotic disease; however, further monitoring is necessary.

Keywords: connective tissue growth factor (ctgf); diffuse lung capacity for carbon monoxide (dlco); forced vital capacity (fvc); idiopathic pulmonary fibrosis (ipf); interstitial lung diseases (ilds); post-covid-19; progressive fibrosing interstitial lung diseases (f-ilds); progressive pulmonary fibrosis.

Figure 1. The baseline CTGF level was significantly higher in all groups compared to the healthy controls

CTGF: Connective tissue growth factor; PF-ILD: progressive fibrosing interstitial lung diseases; IPF: idiopathic pulmonary fibrosis; NSIP: nonspecific interstitial pneumonia; CTD-ILD: connective tissue disease-related interstitial lung disease; FVC: forced vital capacity; DLCO: diffusing capacity for carbon monoxide.

Figure 2. Correlation Matrix

CTGF: Connective tissue growth factor; PF-ILD: progressive fibrosing interstitial lung diseases; IPF: idiopathic pulmonary fibrosis; NSIP: nonspecific interstitial pneumonia; CTD-ILD: connective tissue disease-related interstitial lung disease; FVC: forced vital capacity; DLCO: diffuse lung capacity for carbon monoxide.