Idiopathic pulmonary fibrosis (IPF): Diagnostic routes using novel biomarkers

Abstract

Idiopathic pulmonary fibrosis (IPF) diagnosis is still the diagnosis of exclusion. Differentiating from other forms of interstitial lung diseases (ILDs) is essential, given the various therapeutic approaches. The IPF course is now unpredictable for individual patients, although some genetic factors and several biomarkers have already been associated with various IPF prognoses. Since its early stages, IPF may be asymptomatic, leading to a delayed diagnosis. The present review critically examines the recent literature on molecular biomarkers potentially useful in IPF diagnostics. The examined biomarkers are grouped into breath and sputum biomarkers, serologically assessed extracellular matrix neoepitope markers, and oxidative stress biomarkers in lung tissue. Fibroblasts and complete blood count have also gained recent interest in that respect. Although several biomarker candidates have been profiled, there has yet to be a single biomarker that proved specific to the IPF disease. Nevertheless, various IPF biomarkers have been used in preclinical and clinical trials to verify their predictive and monitoring potential.

Keywords: Breath biomarker; Fibroblast; Idiopathic pulmonary fibrosis; Neoepitope; Oxidative stress biomarker; Sputum biomarker.

Fig. 1

The flowchart of collecting an exhaled breath condensate (EBC) sample, then electrochemical detection of the nitrite content. Reproduced from Ref. [64] under the terms of the Creative Commons CC BY license.

Fig. 2

The flowchart of interleukins affection of the morphology and functions of various cells in idiopathic pulmonary fibrosis (IPF). Reproduced from Ref. [84] under the terms of the Creative Commons CC BY license.

Fig. 3

Baseline comparison of neoepitope concentrations in the discovery cohort in healthy controls and idiopathic pulmonary fibrosis (IPF) suffering participants with stable or progressive disease [92]. Biomarkers: BGM: biglycan; C3M: MMP-9 mediated collagen type III degradation product; CRPM: C-reactive protein metabolite; P3NP: pro-collagen type III N-terminal peptide; C1M: collagen type-I degradation product; C5M:collagen type V degradation product; ELM: elastin degradation product; VICM: citrullinated and MMP-degraded vimentin biomarker; C3A: collagen type III degradation product; C6M: collagen type VI degradation product; ELM2: MMP-9,12 mediated elastin degradation product [92]. Reprinted with permission from Elsevier, copyright 2015 [92].

Fig. 4

Fluorescent probes used to evaluate IPF by detecting the fluctuation of biologically relevant markers (a) H₂O₂ (Adapted with permission from Ref. [112]. Copyright 2021 American Chemical Society), (b) peroxynitrate (ONOO⁻) (Adapted with permission from Ref. [113]. Copyright 2019 American Chemical Society), and (c) glutathione S-transferase (GST) (Adapted with permission from Ref. [114]. Copyright 2019 American Chemical Society).

Fig. 5

(a) Fluorescent images of GGT utilizing Cy-GGT of normal mice as the control group and mice with 28-day bleomycin stimulation as the bleomycin group [119]. (b) Pictures of isolated organs, vis., heart, kidney, liver, lung, and spleen [119]. (c) Routine (H&E) and Masson pathology of each group [119]. (d) Mean intensities of fluorescence images shown in panel (a) [119]. Reprinted with permission from Elsevier, copyright 2020 [119].