Table 1.
Parameters in primary and secondary endpoints
| Primary endpoints | |
|---|---|
|
Biomarkers of exposure |
|
| |
• Urine: Nicotine, cotinine, 3-hydroxycotinine and their glucuronide conjugates, acrolein metabolite (3-HPMA), crotonaldehyde metabolite (HMPMA), TSNA metabolites (total NNAL, total NNN, total NAT, total NAB), 1,3-butadiene metabolite (MHBMA), acrylonitrile metabolite (CEMA) and aromatic amines (4-aminobiphenyl, 3-aminobiphenyl, o-toluidine, 2-aminonaphthalene), plus 9 PAH metabolites (1-Hydroxynapthalene, 2-Hydroxynapthalene, 2-Hydroxyflourene, 1-, 2-, 3-, 4, and 9-Hydroxyphenanthrene, 1-Hydroxypyrene) |
| |
• Salivary cotinine |
| |
• Exhaled CO |
|
Biomarkers of biological effect: |
|
| |
• Urine: F2-isoprostane (8-iso-PGF2 Type III and VI; for oxidative stress) |
| |
• Blood: white blood cells (for cardiovascular disease) |
| |
• Plasma: sICAM-1 (for cardiovascular disease) |
|
Secondary endpoints |
|
|
Biomarkers of exposure |
|
| |
• Urine: urine mutagenicity (Ames test) |
|
Biomarkers of biological effect |
|
| |
• Urine: 8-OHdG, cis-thymidine glycol, 11-dehydrothromboxane B2 |
| |
• Blood: gene expression, neutrophil count, monocyte count |
| |
• Erythrocytes: haemoglobin, superoxide dismutase activity, glutathione peroxidase, glutathione reductase, catalase activity, malondialdehyde |
| |
• Plasma or serum: IL-6, IL-8, ascorbic Acid, dehydroascorbic Acid, total antioxidant capacity, hsCRP (males), fasting (12 h) lipid profile (total cholesterol, LDL, HDL, Triglycerides), fibrinogen, MCP-1, neutrophil elastase, MMP-1, MMP-9, TIMP-1, LTB4, TNF-α, VEGF, oxLDL |
|
Other features |
|
| |
• Filter analysis: MLE to nicotine and ‘tar’ (nicotine-free dry particulate matter [NFDPM]) |
| |
• Sensory testing questionnaire |
| |
• QoL questionnaire |
| |
• Smoking behaviours questionnaire |
| |
• Puffing and inhalation behaviour |
| |
• Pulmonary function test (FEV, FEV1, PEF) |
| |
• Biomarkers of Effective Dose (compliance monitoring) |
| • Haemoglobin adducts in blood: Acrylonitrile (2-Cyanoethylvaline) and 4-ABP |
3-HPMA, 3-Hydroxypropylmercapturic acid; HMPMA, 3-hydroxy-1-methylpropylmercapturic acid; TSNA, Tobacco-specific nitrosamine; NNAL, 4-(methylnitrosamino)-1-(2-pyridyl)-1-butanol; NNN, N-nitrosonornicotine; NAT, N-nitrosoanatabine; NAB, N-nitrosoanabasine; MHBMA, monohydroxybutenylmercapturic acid; CEMA, 2-cyanoethylmercapturic acid; PAH, Polyaromatic hydrocarbons; CO, Carbon monoxide; PGF2, prostaglandin F2; sICAM-1, soluble intercellular adhesion molecule; 8-OHdG, 8-oxo-2′-deoxyguanosine; IL-6, Interleukin 6; IL-8, Interleukin 8; hsCRO, high-sensitivity C-reactive protein; LDL, Low-density lipoprotein; HDL, High-density lipoprotein; MCP-1, Monocyte chemotactic protein-1; MMP-1, Matrix metalloproteinase-1; MMP-9, Matrix metalloproteinase-9; TIMP-1, Tissue inhibitor of metalloproteinase 1; LTB4, Leukotriene B4; TNF-α, Tumour necrosis factor-alpha; VEGF, Vascular endothelial growth factor; oxLDL, oxidised low-density lipoprotein; MLE, mouth level exposure; NFDPM, nicotine free dry particulate matter; QoL, Quality of life; FEV, Forced expiratory volume; FEV1, Forced expiratory volume in 1 second; PEF, Peak expiratory flow; 4-ABP, 4-aminobiphenyl.