Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal disease with a heterogeneous clinical course. This study aimed to evaluate the usefulness of circulating biomarkers in routine IPF clinical practice. We conducted an exploratory study in a cohort of 28 IPF subjects qualified for anti-fibrotic therapy with up to 24 months serial measurements of seven IPF biomarkers, including those that are well-established, Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), matrix metalloproteinase 7 (MMP-7), and more recently introduced ones, cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA-125), chemokine (C-C motif) ligand 18 (CCL18), and periostin. Among studied biomarkers, SP-D had the highest diagnostic accuracy to differentiate IPF subjects from controls, followed by MMP-7 and KL-6. At each study timepoint, KL-6 levels correlated inversely with forced vital capacity % predicted (FVC% pred.), and transfer factor of the lung for carbon monoxide % predicted (TL,CO% pred.), while SP-D levels correlated inversely with FVC% pred. and TL,CO% pred. at 24 months of anti-fibrotic therapy. Baseline KL-6 and CA19-9 concentrations were significantly elevated in patients with progressive disease in comparison to patients with stable disease. In addition, in the progressors subgroup CA19-9 concentrations significantly increased over the second year of study follow-up. In patients with progressive disease, we observed a significant inverse correlation between a change in SP-D levels and a change in FVC% pred. in the first year of treatment, whereas in the second year a significant inverse correlation between a change in KL-6 levels and a change in FVC% pred. was noted. Our study findings support the view that both well-established IPF biomarkers, including KL-6, SP-D, and MMP-7, and more recently introduced ones, like CA19-9, have the potential to support clinical practice in IPF.
Highlights
These results add further evidence supporting the potential role of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and cancer antigen 19-9 (CA19-9) as prognostic biomarkers in Idiopathic pulmonary fibrosis (IPF)
From control subjects with high diagnostic accuracy. These results indicate that the measurements of serum concentrations of SP-D, matrix metalloproteinase 7 (MMP-7), and KL-6 may offer a potential tool to support an early diagnosis of IPF
We have shown that baseline KL-6 and CA19-9 levels can discriminate between patients with progressive and stable disease
Summary
Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive lung disease with an inevitable fatal outcome. The clinical course of IPF is outlined by a progressive decline of lung function, physical activity limitation, impairment of quality of life, and premature death. Chronic and repetitive micro-injuries to the alveolar epithelium caused by exposure to various noxious stimuli [4,5,6,7] lead in genetically predisposed individuals to subsequent dysfunction of the alveolar epithelial cells (AECs) which is central to the initiation and perpetuation of the pathogenic process in IPF. Aberrant activation of AECs leads to the production of mediators involved in the migration, proliferation, and activation of fibroblasts, their differentiation to myofibroblasts, and consequent excessive and chaotic secretion of extracellular matrix (ECM) proteins, leading to progressive lung parenchyma destruction characteristic for IPF [8]
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