Biomarkers of Potential Harm: Summary of an FDA-Sponsored Public Workshop

Chang, Cindy M.; Cheng, Yu Ching; Cho, Taehyeon M.; Mishina, Elena V.; Valle-Pinero, Arseima Y. Del; Bemmel, Dana M. van; Hatsukami, Dorothy K.

doi:10.1093/ntr/ntx273

Cited by 45 publications

(55 citation statements)

References 76 publications

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“…The present research on IEGs after acute WP exposure is the first of its kind and addresses the need for genetic biomarkers that are specifically tailored to WP use 139. We adopted previous approaches to show that IEGs may potentially quantify and predict harmful effects in humans, known as biomarkers of potential harm, based on the magnitude and direction of expression 140–142. Furthermore, IEG testing in the nasal epithelium and gingiva (the gums) is a promising and non-invasive alternative with clinical relevance 143 144.…”

Section: Discussionmentioning

confidence: 99%

Immune modulation by chronic exposure to waterpipe smoke and immediate-early gene regulation in murine lungs

et al. 2019

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ObjectiveWe investigated the effects of chronic waterpipe (WP) smoke on pulmonary function and immune response in a murine model using a research-grade WP and the effects of acute exposure on the regulation of immediate-early genes (IEGs).MethodsWP smoke was generated using three WP smoke puffing regimens based on the Beirut regimen. WP smoke samples generated under these puffing regimens were quantified for nicotine concentration. Mice were chronically exposed for 6 months followed by assessment of pulmonary function and airway inflammation. Transcriptomic analysis using RNAseq was conducted after acute exposure to characterise the IEG response. These biomarkers were then compared with those generated after exposure to dry smoke (without water added to the WP bowl).ResultsWe determined that nicotine composition in WP smoke ranged from 0.4 to 2.5 mg per puffing session. The lung immune response was sensitive to the incremental severity of chronic exposure, with modest decreases in airway inflammatory cells and chemokine levels compared with air-exposed controls. Pulmonary function was unmodified by chronic WP exposure. Acute WP exposure was found to activate the immune response and identified known and novel IEG as potential biomarkers of WP exposure.ConclusionChronic exposure to WP smoke leads to immune suppression without significant changes to pulmonary function. Transcriptomic analysis of the lung after acute exposure to WP smoke showed activation of the immune response and revealed IEGs that are common to WP and dry smoke, as well as pools of IEGs unique to each exposure, identifying potential biomarkers specific to WP exposure.

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Section: Discussionmentioning

confidence: 99%

Immune modulation by chronic exposure to waterpipe smoke and immediate-early gene regulation in murine lungs

et al. 2019

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“…[1, 2] The urinary metabolites “prostaglandin E 2 metabolite” (PGE-M) and ( Z )-7-[1 R ,2 R ,3 R ,5 S )-3,5-dihydroxy-2-[( E ,3 S )-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8- iso -PGF 2α ) are accepted biomarkers of inflammation and oxidative damage, respectively, and are part of a group of measures that have been termed “biomarkers of potential harm”. [3–6] Fig 1.…”

Section: Introductionmentioning

confidence: 99%

Effects of cessation of cigarette smoking on eicosanoid biomarkers of inflammation and oxidative damage

et al. 2019

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The urinary metabolites “prostaglandin E 2 metabolite” (PGE-M) and ( Z )-7-[1 R ,2 R ,3 R ,5 S )-3,5-dihydroxy-2-[( E ,3 S )-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8- iso -PGF 2α ) are biomarkers of inflammation and oxidative damage, respectively, and are elevated in cigarette smokers. Relatively little is known about the effects of smoking cessation on these biomarkers. To investigate this, current cigarette smokers interested in quitting were recruited and invited to participate in a smoking cessation study where varenicline (Chantix) and brief supportive behavioral counseling were offered at each visit after baseline. Subjects returned to the clinic during the 12 week treatment phase for 9 visits post cessation on days 3, 7, 14, 21, 28, 42, 56, 70 and 84. Urine samples were collected at each visit and analyzed by liquid chromatography-tandem mass spectrometry for PGE-M, 8- iso -PGF 2α , and cotinine. Cotinine values demonstrated that 15 of 38 subjects quit smoking for the entire 84 day period. Significant decreases in mean levels of PGE-M and 8- iso -PGF 2α per milligram creatinine were observed in these subjects, by 44% (p = 0.0014) and 27% (p<0.001), respectively. The results of this study demonstrate that cessation of smoking for 84 days results in modest but significant declines in urinary PGE-M and 8- iso -PGF 2α indicating reductions in systemic inflammation and oxidative damage. Given that levels were only modestly decreased, these markers are not specific to tobacco-smoke exposure. The modest declines in these biomarkers should be considered when planning studies with ex-smokers. There is a “hangover” from smoking that lasts at least 3 months.

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“…These decreases in biomarker levels are far less than observed for typical biomarkers of exposure, which decrease by 39–92% within only 3 days after smoking cessation [34]. While biomarkers of exposure depend mainly on specific toxicant exposures which stop upon smoking cessation, biomarkers such as 8- iso -PGF 2α and PGE-M, which have been termed “biomarkers of potential harm” [4], result from alterations in physiologic processes related to oxidative damage and inflammation [35, 36]. PGE-M has also been described as a potential cancer biomarker and its levels have been positively associated with high saturated fat intake, obesity, and poor self-reported health status in addition to cigarette smoking and other factors [37].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a recent nested case-control study within the prospective Shanghai Cohort Study demonstrated a significant relationship of 8- iso -PGF 2α to lung cancer incidence in cigarette smokers [3]. Thus, 8- iso -PGF 2α and PGE-M are considered “biomarkers of potential harm” reflecting early biological effects strongly associated with disease [4].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal stability in cigarette smokers of urinary eicosanoid biomarkers of oxidative damage and inflammation

et al. 2019

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The urinary metabolites ( Z )-7-[1 R ,2 R ,3 R ,5 S )-3,5-dihydroxy-2-[( E ,3 S )-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8- iso -PGF 2α ), an F2-isoprostane and biomarker of oxidative damage, and “prostaglandin E 2 metabolite” (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8- iso -PGF 2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8- iso -PGF 2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8- iso -PGF 2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8- iso -PGF 2α and PGE-M, respectively, indicating fair longitudinal stability for 8- iso -PGF 2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8- iso -PGF 2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

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Biomarkers of Potential Harm: Summary of an FDA-Sponsored Public Workshop

Abstract: This paper synthesizes the main findings from the 2016 FDA-sponsored workshop focused on biomarkers of potential harm (BOPH) and highlights research areas that could further strengthen the science around BOPH and their applicability to tobacco regulatory science.

Cited by 45 publications

References 76 publications

Immune modulation by chronic exposure to waterpipe smoke and immediate-early gene regulation in murine lungs

Immune modulation by chronic exposure to waterpipe smoke and immediate-early gene regulation in murine lungs

Effects of cessation of cigarette smoking on eicosanoid biomarkers of inflammation and oxidative damage

Longitudinal stability in cigarette smokers of urinary eicosanoid biomarkers of oxidative damage and inflammation

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