Acute Exacerbations of Interstitial Lung Diseases: Focus on Biomarkers

Abstract

Interstitial lung diseases (ILDs) are a large group of pulmonary disorders characterized histologically by the cardinal involvement of the pulmonary interstitium. The prototype of ILDs is idiopathic pulmonary fibrosis (IPF), an incurable disease characterized by progressive distortion and loss of normal lung architecture through unchecked collagen deposition. Acute exacerbations are dramatic events during the clinical course of ILDs, associated with high morbidity and mortality. Infections, microaspiration, and advanced lung disease might be involved in the pathogenesis of acute exacerbations. Despite clinical scores, the prediction of the onset and outcome of acute exacerbations is still inaccurate. Biomarkers are necessary to characterize acute exacerbations better. We review the evidence for alveolar epithelial cell, fibropoliferation, and immunity molecules as potential biomarkers for acute exacerbations of interstitial lung disease.

Keywords: acute exacerbations; biomarkers; interstitial lung diseases.

Figure 1

Potential biomarkers in AE-ILD and their cellular source. Due to various stimuli (infections, microaspiration, air pollution, stress, intrinsic acceleration of the underlying fibrosis), injured alveolar epithelial cells and disrupted epithelial barrier lead to the secretion of KL-6, SP-A, and SP-D. Increased KL-6 promotes fibroblast activation through TGF-b signaling. SP-D further aggregates ECM deposition. Matrix metalloproteinase-mediated degradation of collagen leads to the release of versican and ADAM. Periostin is also a marker of increased matrix turnover. During AE-ILDs, lung inflammation is driven by upregulation of macrophage activation pathways. IL-8 and CXCL1 mainly contribute to the neutrophil influx. Neutrophils release numerous proteases and produce reactive oxygen species. Vascular and endothelial damage contributes to the influx of neutrophils.