Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 3. Biomarkers of biological effect

Figures & data

Table 1. Biomarkers of biological effect.

Indication	Marker	Abbreviation	Media	Units	Method^a	Lab
Oxidative damage and  inflammation	Isoprostane isomers and metabolites	iPF2α-III; 2,3-dinor-iPF2α-III; (±)5-iPF2α-VI; 8,12-iso-iPF2α-VI; PGF2α	Urine	μg/24 h	LC–MS/MS (Yan et al., 2006)^b	RJRT
Inflammation	Soluble intercellular adhesion molecule 1	sICAM1	Plasma/serum	ng/mL	Immunoassay	CCLS
Inflammation	C-reactive protein	CRP	Plasma/serum	mg/L	Immunonephelometry	CCLS
Inflammation	White blood cells	WBC	Whole blood	GI/L	CBC	CCLS
Hypercoaguable state	Fibrinogen	–	Plasma/serum	g/L	Photometry	CCLS
Hypercoaguable state	Homocysteine	–	Plasma/serum	μmol/L	Immunoassay	CCLS
Hypercoaguable state	Hematocrit	HCT	Whole blood	%	CBC	CCLS
Hypercoaguable state	Hemoglobin	HgB	Whole blood	g/L	CBC	CCLS
Hypercoaguable state	Platelets	–	Whole blood	GI/L	CBC	CCLS
Insulin resistance	Hemoglobin A1c	HgBA1c	Blood	%	LC–UV/Vis	CCLS
Cardiac risk	High density lipoprotein	HDL	Plasma/serum	mmol/L	Enzymatic	CCLS
Cardiac risk	Low density lipoprotein	LDL	Plasma/serum	mmol/L	Enzymatic	CCLS
Cardiac risk	HDL/LDL	–	Plasma/serum	–	–	CCLS
Cardiac risk	Oxidized LDL	OxLDL	Plasma/serum	U/L	Immunoassay	Pacific Biometrics^c
Cardiac risk	Triglycerides	–	Plasma/serum	mmol/L	Enzymatic	CCLS
Endothelial function	Circulating endothelial precursor cells	CEP	Whole blood	counts	Flow cytometry (Kondo et al., 2004)	CLL
DNA damage	Sister chromatid exchange	SCE	Whole blood	mean events	Microscopy (Goto et al., 1978; Latt, 1974; OECD, 1986)	CLL

CBC, complete blood count; CCLS, Covance Central Laboratory Services (Indianapolis, IN); CLL, Covance Laboratory Ltd. (Harrogate, UK); LC–MS/MS, liquid chromatography tandem mass spectrometry; LC–UV/Vis, liquid chromatography with ultraviolet/visible spectroscopic detection; RJRT, R.J. Reynolds Tobacco Co. (Winston Salem, NC); –, not applicable.

^a Measures are standard assays conducted under CLIA guidelines and control except where noted.

^b LOD, LOQ: iPF_2α-III 15, 50; 2,3-dinor 60, 200; iPF_2α-VI 60, 200; 8,12-iso 60, 200; PGF_2α 30, 100.

^c Seattle, WA.

Table 2. Biomarkers, smokers versus never smokers, intent-to-treat, week 0.

		Smokers			Never smokers
Biomarker^a	Units	n	Mean	SD	n	Mean	SD	p Value^b
Inflammation/Oxidative damage
iPF2α-III	μg/24 h	125	0.73	0.50	29	0.40	0.29	<0.0001
PGF2α	μg/24 h	125	1.73	0.92	29	1.44	0.88	0.1143
2,3-dinor-iPF2α-III	μg/24 h	125	4.73	3.52	29	3.63	2.77	0.0746
(±)5-iPF2α-VI	μg/24 h	125	2.56	1.26	29	1.94	1.15	0.0136
8,12-iso-iPF2α-VI	μg/24 h	125	4.77	2.66	29	3.61	2.39	0.0254
sICAM1	ng/mL	126	308	94.3	30	231	45.9	<0.0001
WBC	GI/L	129	8.05	1.96	32	6.30	1.80	<0.0001
CRP	mg/L	122	3.55	4.59	32	5.87	17.4	0.4589
Lipids
HDL	mmol/L	115	1.23	0.36	30	1.38	0.37	0.0587
LDL	mmol/L	109	3.40	0.90	29	3.24	0.90	0.3930
HDL/LDL	–	109	0.40	0.18	29	0.46	0.18	0.0981
OxLDL	U/L	108	98.4	26.1	27	88.1	24.2	0.0598
Triglycerides	mmol/L	115	2.02	1.34	30	1.56	1.50	0.1291
Hypercoaguable state
Fibrinogen	g/L	119	3.13	0.72	29	3.23	1.03	0.6309
Platelets	GI/L	128	271	60.0	32	261	55.1	0.3688
HCT	%	129	45.4	3.7	32	43.1	3.8	0.0035
HgB	g/L	129	148	12.8	32	140	12.9	0.0023
Homocysteine	μmol/L	130	9.49	4.04	32	8.27	1.85	0.0126
Insulin resistance
HgBA1c	%	130	5.53	0.64	32	5.42	0.34	0.1649
Endothelial function
CEP	Counts	117	32.2	77.3	29	20.0	33.6	0.2011
DNA damage
SCE	mean events	124	7.52	1.26	30	6.68	1.12	0.0006

^aSee Table 1 for abbreviations.

^bp Values were generated by two-sample t-test with unequal variance.

Figure 1. Percent change in sICAM1 over time in smokers switched to tobacco-heating cigarettes (TH), snus or ultra-low machine yield tobacco-burning cigarettes (TB). *Statistically significant reduction (p<0.05) from week 0.

Figure 2. Percent change in WBC over time in smokers switched to tobacco-heating cigarettes (TH), snus or ultra-low machine yield tobacco-burning cigarettes (TB). *Statistically significant reduction (p<0.05) from week 0.

Figure 3. Percent change in SCE mean events over time in smokers switched to tobacco-heating cigarettes (TH), snus or ultra-low machine yield tobacco-burning cigarettes (TB). *Statistically significant difference (p<0.05) from week 0.

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