Differenzial analysis of antioxidative capacities in the alveolar compartment of diffuse parenchymal lung disorders and diseased controls

Diffuse parenchymal lung disorders (DPLDs) are a heterogeneous group of rare entities including granulomatous DPLDs like sarcoidosis, and idiopathic interstitial pneumonias like non specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Common hallmarks of these entities are inflammation and fibrosis of lung interstitium and small airways. In the normal lung the antioxidant defense system protects the alveolar compartment from damaging effects of environmental oxidative influence. In DPLDs the regulation of antioxidants are thought to be disturbed. Searching for biomarkers to be used as support in differenzial diagnosis of interstitial DPLDs we analyzed low molecular weight antioxidants in the bronchoalveolar lavage fluids of patients with sarcoidosis, NSIP, and UIP compared to COPD and EAA as diseased controls. In a first approach we investigated glutathione (GSH), 8-isoprostane and superoxide dismutases (SOD) in the BALF of 147 individuals, namely 73 patients with sarcoidosis, 20 with UIP, 15 with NSIP, and as diseased controls 14 with EAA and 25 with COPD.. GSH was determined by a commercially available glutathione assay (Cayman Chemical). 8-isoprostane was detected using a competitive assay (Cayman Chemical 8-Isoprostane EIA Kit). The superoxide dismutases assay kit (Cayman Chemical) was used to quantify SOD in BALFs. Quantification of GSH revealed highest mean concentrations in BALFs of patients with Sarcoidosis (1.17µM) followed by UIP (1.02µM) and NSIP (0.87µM). Although GSH concentrations in DPLDs showed significant differences, diseased controls as COPD presented with significantly higher concentrations (2.06µM; up to p<0.0001 and EAA with significantly lower (0.61µM; p<0.05) GSH concentrations. Although not significant, highest amounts of 8-isoprostane were found in patients with sarcoidosis (8.20pg/ml) followed by NSIP (6.58pg/ml) and UIP (3.99pg/ml). This was also true for detection of SOD in BALFs (sarcoidosis 0.42U/ml; NSIP 0.37U/ml and UIP 0.31U/ml). To date preliminary data do not support the usage of GSH, 8-isoprostane or SOD as differenzial biomarkers in BALFs of patients with sarcoidosis, NSIP and UIP. However, analyses will be continued to improve the statistical power of this studies.

Funding: This study was funded by the BMBF (GOLD.net: BMBF 01GM0861)