Table 1.
Summary of EBC markers of oxidative stress and antioxidant capacity including S100 proteins in COPD and lung cancer (legend: “↑”: elevated, “↓”: decreased, “≈”: no difference, “×”: undetectable).
| Category | Biomarkers | COPD patients | Lung cancer patients | ||
|---|---|---|---|---|---|
| EBC (compared to healthy volunteers) | EBC (compared to smokers or ex-smokers) | EBC (compared to healthy volunteers) | EBC (compared to specific controls) | ||
| Markers of oxidative stress | |||||
| Reactive oxygen species | Hydrogen peroxide | ↑ [34, 135–138] | ↑ [34] | ↑ [135] | |
|
| |||||
| Reactive nitrogen species | Nitric oxide | ↑ [139–144] | ↑ [139, 141] | ↑ [140] | ↑ (controls = cancer patients) [142] |
| Nitrite | ↑ [145] | ↑ [145] | ↑ (controls = cancer patients) [142] | ||
| Nitrate | High variability [146] | ↓ (controls = cancer patients) [142] | |||
| ≈ [141, 147] | |||||
| Peroxynitrite | ↑ [148, 149] | ↑ [148, 149] | |||
|
| |||||
| Lipid peroxidation products/eicosanoids (arachidonic acid derivatives) | 8-isoprostane | ↑ [137, 148, 150, 151] | ↑ [34, 148, 150] | ↑ [135] | |
| ≈ (controls = healthy smokers) [152] | |||||
| Malondialdehyde | ↑ [138, 153] | ↑ [153] | ↑ [154] | ||
| ≈ [137, 155] | ≈ [137] | ||||
| Leukotrienes B4 | ↑ [156–158] | ↑ [159] | ↑ (controls = patients without pulmonary disease) [156] | ||
| Leukotriene C4 | ↑ [160] | ||||
| Leukotriene D4 | ↑ [160] | ||||
| Leukotriene E4 | ≈ [158] | ↑ [160] | |||
| Prostaglandin E2 | ↑ [158] | ||||
| Thromboxane B2 (the stable form of thromboxane A2) | ↓ [158] | ||||
| Prostaglandin D2-methoxime | ≈ [158] | ||||
| Prostaglandin F2α | ↑ [158] | ||||
|
| |||||
| Cytokines and proteins | Tumour necrosis Factor-α | ≈ [47] | ↑ [161] | ↑ (controls = smokers without COPD or lung cancer) [152] | |
| Interleukin-6 | ↑ [162] | ↑ [163] | |||
| ≈ [47] | |||||
| Interleukin-8 | ≈ [47, 164] | ≈ [164] | ↑ (controls = patients without pulmonary diseases) [156] | ||
| Metaloproteinase-9 | ↑ [134] | ↑ (controls = patients without pulmonary diseases) [165] | |||
| Vascular endothelial growth factor | ↑ (controls = healthy smokers) [152] | ||||
| Endothelin-1 | ↑ [166] | ↑ [167] | |||
| ↑ [168] | |||||
|
| |||||
| Volatile organic compounds | Alkanes, alkane derivatives, benzene derivatives | ↑ (exhaled ethane) [169] | ↑ [170, 171] | ||
|
| |||||
| Heme breakdown product | Carbon monoxide | ↑ [144] | ↑ [144] | ||
|
| |||||
| pH | ↓ [164, 172–175] | ≈ [173] | ≈ [172] | ||
|
| |||||
| Deoxyribonucleic acid mutations | 3p microsatellite alterations | ↑ [176] | |||
| Tumour suppressor gene P53 mutations | ↑ [177] | ||||
| Oncogene KRAS | ↑ [178] | ||||
| Epidermal growth factor receptor (EGFR) gene mutations | ↑ (in small number of heavy smokers with squamous cell carcinoma) [179] | ||||
| Gene promoter methylation mutations | ↑ [180] | ||||
| Mitochondrial DNA mutations | ↑ (controls = smokers, exsmokers without chronic respiratory diseases, respiratory illnesses, or lung cancer) [70] | ||||
|
| |||||
| Viruses | Human papilloma virus | ↑ (controls = patients suspected of lung cancer but with negative cytology) [181] | |||
|
| |||||
| Markers measuring antioxidant capacity | |||||
| Enzymes | Superoxide dismutase | ↑ (controls = patients without pulmonary diseases) [182] | |||
|
| |||||
| Nonenzymatic antioxidants | Ascorbic acid/vitamin C | ↓ (↑ in percentage degradation/oxidation rate) [161] | |||
| Urate | × [175] | × [175] | |||
| Ferritin | ↑ (controls = patients affected by transudative pleural effusion and without pulmonary diseases) [182] | ||||
| Bilirubin | ≈ [175] | ≈ [175] | |||