TABLE 2.
Summary of the oxidative stress biomarkers analysed in different biological specimens of IPF patients.
| Specimen | Comparison (n) | Biomarker | Lung function/severity disease correlation | Reference |
|---|---|---|---|---|
| ELF | IPF (15) vs. Ctrl (19) | ↓tGSH | No correlation | Cantin et al. (1989) |
| ↔GSH/GSH + GSSG | ||||
| ELF | IPF (10) vs. Ctrl (19) | ↓tGSH | N/A | Borok et al. (1991) |
| ↓GSH | ||||
| ELF | IPF (17) vs. Ctrl (14) | ↓tGSH | No correlation | Meyer et al. (1994) |
| BALF | ↔tGSH | |||
| BALF | IPF (12) vs. Ctrl (31) | ↓GSH | N/A | Rahman et al. (1999) |
| ↔GSSG | ||||
| ↓GSH/GSSG | ||||
| Sputum | IPF (16) vs. Ctrl (15) | ↓tGSH | ↑disease severity | Beeh et al. (2002) |
| Plasma | ↓VC | |||
| BALF | IPF (16) vs. Ctrl (20) | ↔GSH | No correlation | Markart et al. (2009) |
| ↑GSSG | ||||
| Blood | IPF (22) vs. Ctrl (29) | ↓tGSH | No correlation | Muramatsu et al. (2016) |
| ↓tGSH/GSSG | ||||
| ↑GSSG | ↓FVC | |||
| Blood | IPF (11) vs. Ctrl (9) | ↓GSH | N/A | Veith et al. (2017) |
| ↔GSSG | ||||
| Serum | IPF (37) vs. Ctrl (6) | ↑lipid peroxidation | ↑disease severity | Jack et al. (1996) |
| ↓VC | ||||
| ↑TBARS | No correlation | |||
| Plasma | IPF (12) vs. Ctrl (31) | ↑MDA | N/A | Rahman et al. (1999) |
| BALF | ↓TEAC | |||
| BALF | IPF non-smokers (14) vs Ctrl non-smokers (9) | ↑Carbonyl proteins | N/A | Lenz et al. (1996) |
| BALF | IPF (9) vs. Ctrl (5) | ↑Carbonyl proteins | N/A | Lenz et al. (2004) |
| BALF | IPF (13) vs. Ctrl (5) | ↑Carbonyl proteins | N/A | Rottoli et al. (2005) |
| BALF | IPF (15) vs. Ctrl (8) | ↑Carbonyl proteins | N/A | Bargagli et al. (2007) |
| EBC | IPF (16) vs. Ctrl (15) | ↑8-isoprostane | No correlation | Psathakis et al. (2006) |
| ↑H2O2 | ↓DLCO | |||
| Plasma and urine | IPF (29) vs. Ctrl (6) | ↑Pl-isoprostanes | N/A | Jackson et al. (2010) |
| ↔Ur- H2O2 | ||||
| IPF at rest (29) vs. IPF after physical exercise | ↔Pl-isoprostanes | |||
| ↓Pl-TAC | ||||
| ↑Ur-isoprostanes | ||||
| ↔Ur- H2O2 | ||||
| EBC | IPF (20) vs. Ctrl (20) | ↑8-isoprostane | No correlation | Chow et al. (2012) |
| ↔ NOx | ||||
| ↔ H2O2 | ||||
| ↑3-NT | ↓FVE1, ↓FVC, ↓VC, ↓TLC | |||
| Serum and BALF | IPF (16) vs. Ctrl (17) | ↑8-isoprostane | N/A | Malli et al. (2013) |
| EBC | IPF (6) vs. Ctrl (6) | ↑8-isoPGF2α | N/A | Shimizu et al. (2014) |
| Plasma | IPF (21) vs. Ctrl (12) | ↑hydroperoxides | ↑dyspnea severity | Daniil et al. (2006) |
| ↓ FVC ↓DLCO | ||||
| Serum | IPF (43) vs. Ctrl (30) | ↑hydroperoxides | ↓FVC ↓DLCO | Matsuzawa et al. (2015) |
| ↑acute exacerbation | ||||
| BALF | IPF (16) vs. Ctrl (20) | ↑uric acid | N/A | Markart et al. (2009) |
| ↑ascorbic acid | ||||
| ↑vitamin A | ||||
| ↑vitamin E | ||||
| Blood | IPF (11) vs. Ctrl (9) | ↓uric acid (not sig) | N/A | Veith et al. (2017) |
| ↓ascorbic acid (not sig) | ||||
| ↓TEAC | ||||
| Lung tissue | IPF (10) vs. Ctrl (5) | ↔ECSOD | N/A | Kinnula et al., 2006 |
| IPF fibrotic areas vs IPF normal areas | ↓ECSOD | |||
| Lung tissue | IPF (10) vs. Ctrl (310) | ↔PrxII | N/A | Vuorinen et al. (2008) |
| Lung tissue | IPF (7) vs. Ctrl (7) | ↔NRF2 | N/A | Mazur et al. (2010) |
| ↑SRX1 | ||||
| IPF hyperplastic epithelium vs IPF normal epithelium | ↑NRF2 | |||
| ↑KEAP1 |
3-NT, 3-nitrotyrosine; BALF, bronchoalveolar lavage fluid; Ctrl, control; DLCO, diffusing capacity of the lungs for carbon monoxide; EBC, expired breath condensate; ECSOD, Extracellular Superoxide Dismutase; ELF, epithelial lining fluid; FEV, forced expiratory volume; FVC, forced vital capacity; GSH, glutathione; GSSG, oxidized glutathione; IPF, idiopathic pulmonary fibrosis; KEAP1, Kelch like-ECH-associated protein 1; MDA, malondialdehyde; N/A, not available; not sig, not significative; NOx, NADPH, oxidases; NRF2, nuclear factor erythroid 2-related factor 2; Pl, plasma; PrxII, peroxiredoxin II; SRX1, sulfiredoxin-1; TAC, total antioxidant capacity; TBARS, thiobarbituric acid reactive substances; TEAC, trolox equivalent antioxidant capacity; tGSH, total glutathione; Ur, urine.