Serum surfactant proteins‐A and ‐D as biomarkers in idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials.The goals of this study were to determine whether serum levels of surfactant protein‐A (SP‐A) or surfactant protein‐D (SP‐D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP‐A or SP‐D levels predict outcome in patients with IPF.The authors found that serum SP‐A and SP‐D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP‐D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP‐A and SP‐D levels were highly predictive of survival in patients with IPF.This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins‐A and ‐D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.

KL-6 and Surfactant Proteins A and D in Serum and Bronchoalveolar Lavage Fluid in Patients with Acute Eosinophilic Pneumonia

“…Reports have demonstrated increased KL-6 levels in the BALF of fibrotic interstitial lung disease, such as IPF or sarcoidosis (7,14). The serum levels of KL-6 in patients with nonfibrotic interstitial lung disease, such as bronchiolitis obliterans organizing pneumonia (BOOP) or eosinophilic pneumonia (EP), did not differ from those of normal control subjects.…”

“…Therefore, SP-D levels might appear to be more sensitive than SP-A levels at reflecting the damage to or release of these molecules from epithelial cells as a consequence of eosinophilic inflammation in AEP lungs. The mechanism by which serum SP-A and SP-D levels are elevated in patients with interstitial lung disease has been thought to be that alveolar type II cells cause hyperplasia from stimulation, such as through inflammation, and generate the creation of biomarkers; in addition, the destruction of alveolar epithelium and endothelium might cause hyperlucent into blood (14,21). Furthermore, the molecular weight of a completed unit of SP-A and SP-D is estimated to be 650 kd and 540 kd, respectively, so SP-D is a slightly smaller than SP-A (22,23).…”

“…KL-6 causes chemotaxis of fibroblast and induction of fibrosis in patients with interstitial pneumonias (14). Reports have demonstrated increased KL-6 levels in the BALF of fibrotic interstitial lung disease, such as IPF or sarcoidosis (7,14).…”

“…Increased KL-6 levels have been found in the BALF of patients with a fibrotic interstitial lung disease, such as IPF or sarcoidosis (7,14). On the other hand, SP-A or SP-D levels in BALF from patients with IPF or interstitial pneumonia with collagen vascular disease (CVD-IP) have been reported to be either reduced (25)(26)(27) or unchanged (28,29).…”

“…Several studies have measured the levels of KL-6, SP-A, and SP-D in the bronchoalveolar lavage fluid (BALF) of IPF patients in attempt to understand how those levels become elevated (14)(15)(16). It has been thought that the destruction of the alveolar epithelium and endothelium might cause hyperlucent blood.…”