Plasma biomarkers for diagnosis and prognosis in interstitial lung disease (ILD)

Background: Distinguishing ILD subtypes can be challenging in clinical practice. We evaluated plasma biomarkers (pBM) for their ability to differentiate between inflammatory and fibrotic ILD subtypes, and predict disease progression.

Methods: Data including serial HRCT, pulmonary function tests (PFTs) and pBM were collected in a prospective observational ILD study. CT visual fibrosis scoring (VFS) as well as CALIPER analysis were performed and pBM measured by Multiplex Luminex and ELISA assays. Association of selected pBM at baseline were correlated with VFS at visit 3, as well as differences between inflammatory and fibrotic ILD subtypes such as hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF).

Results: 55 patients were included. Biomarkers, such as MMP7, KL6, SPA1 and YKL40 together with PFTs correlated with imaging biomarkers longitudinally over 3 visits. A number of pBM at visit 1 were associated with VFS at visit 3, and the ratio MMP7/MMP9 together with KL6 differed significantly among the ILD subtypes HP and IPF (Figure 1). The multivariable logistic regression analysis, Log(KL6), Log(MMP7/MMP9), CCL26 and MMP9 at visit 1 distinguished between the disease subtypes HP vs IPF (AUC 0.94).

Conclusion: Combining imaging, pBM and PFTs can aid in differentiating ILD subtypes and predicting disease progression. For example, KL6, a marker of epithelial injury, and MMP7/MMP9 show promise in separating HP vs IPF.