Our results demonstrate that, despite lower reported exposure to ETS, African-American children have significantly higher levels of both serum and hair cotinine. These findings were partially explained by smaller home sizes among African-American children. Still, the racial differences in cotinine persisted after accounting for housing characteristics and exposures that occurred outside the home. Consistent with this study, Knight et al. (1996)
similarly found that black children had significantly higher levels of cotinine compared with white children, despite lower ETS exposure. In contrast, Mannino et al. (2001a)
found no differences by race in a cohort of tobacco-exposed children. However, neither study accounted for housing characteristics or ETS exposure outside the home. Our study clearly demonstrates that even after accounting for reported exposure and potential modifying environmental factors, African-American children have significantly higher levels of both serum and hair cotinine.
There are at least two possible explanations for why African Americans may have higher levels of cotinine. One explanation could be a racial difference in their metabolism of tobacco-related products. A number of recent studies have found that African-American smokers metabolize nicotine and cotinine more slowly than do white smokers. Perez-Stable and colleagues infused deuterium-labeled nicotine and cotinine into subjects and monitored for nicotine and cotinine clearances (Benowitz et al. 1999
; Perez-Stable et al. 1998
). They found that African-American subjects had a higher total clearance and nonrenal clearance of cotinine and longer serum half-life of cotinine. Some authors hypothesize that polymorphisms in the cytochrome P450 2A6 (CYP2A6
) gene might explain racial differences in enzyme levels and enzyme activity (Ahijevych et al. 2002
; Benowitz et al. 1999
; Tricker 2003
). However, the size of the cotinine differences observed in this study would likely require quite substantial genetic variation. Results from a study completed by Paschke et al. (2001)
suggest that CYP2A6
polymorphisms occur infrequently in both African-American and white populations, 0.3 and 1.3%, respectively. Small differences in the prevalence of CYP2A6
polymorphisms may not fully explain the striking differences in cotinine and health outcomes. Thus, the attribution of a genetic basis for racial differences in cotinine should be made cautiously, because race is at best a crude marker for genetic variation (Cooper 2003
; Cooper et al. 2003
Differences in additives to cigarettes commonly smoked by African Americans could also explain the observed racial differences in cotinine. Approximately 80% of African-American smokers report using mentholated tobacco products, compared with 20% of white smokers (Kabat et al. 1991
). Although a complete understanding of this preference is unclear, it is well documented that tobacco companies have targeted their marketing campaigns of mentholated brands toward African Americans (Balbach et al. 2003
). On average, mentholated brands have significantly higher levels of tar and nicotine (Federal Trade Commission 2000
). In a randomized crossover trial, Benowitz et al. (2004)
found that African-American subjects had higher levels of both serum nicotine and blood carboxyhemoglobin while smoking mentholated tobacco products than when they were smoking nonmentholated tobacco products. Ahijevych et al. (2002)
found that white and African-American women who smoked mentholated cigarettes had higher levels of serum cotinine compared than did white women who smoked nonmentholated tobacco products. Because no African-American women smoked nonmentholated products, this group could not be assessed. Although these studies demonstrate an effect of menthol on nicotine and cotinine metabolism, they were all completed in adult smokers. It is not clear whether this relationship between menthol and cotinine exists among children exposed to ETS.
Although racial differences in cotinine were present for hair and serum, the relative racial difference was greater for hair cotinine. The larger racial difference for hair cotinine compared with serum cotinine may be due to multiple factors. First, there may be less variability in hair cotinine. Serum cotinine measures short-term ETS exposure (3–4 days), whereas hair cotinine measures ETS exposure in the prior month (Al-Delaimy 2002
; Al-Delaimy et al. 2002
). Because hair cotinine measures long-term ETS exposure, it is less vulnerable to everyday variability in ETS exposure and metabolism (Al-Delaimy 2002
). Second, there may be racial differences in the use of dyes and hair treatments, which could affect hair cotinine levels. Pichini et al. (1997)
found that use of dyes and hair treatments decreased levels of hair cotinine. Last, there may be differences in other unmeasured factors. Despite these relative differences, our results consistently demonstrate that African-American children have higher levels of cotinine in both hair and serum.
Racial differences in cotinine metabolism raise questions about whether cotinine could help explain the racial differences in tobacco-related morbidity and mortality. Although cotinine is often considered an inert biomarker, recent literature suggests that cotinine exhibits biologic activity. Cotinine is mitogenic on vascular smooth muscle cells in a dose-related fashion (Carty et al. 1997
) and has been shown to reduce the survival of hippocampal neurons and to decrease neurite function (Audesirk and Cabell 1999
). Further research is necessary to ascertain whether prolonged exposure to nicotine and cotinine contributes to the observed racial differences in childhood asthma morbidity and mortality.
Our study has some limitations. First, we measured ETS exposure using parent report. A systematic underreporting of tobacco use by African-American parents could explain the racial differences in serum and hair cotinine. However, prior studies suggest this is unlikely (Caraballo et al. 2001
; Clark et al. 1996b
; Wills and Cleary 1997
). For example, Clark et al. (1996b)
found no racial difference in the reporting of tobacco use relative to the number of cigarette butts collected. Furthermore, our study measured the level of particulate matter in the main activity room at each residence. Consistent with lower reported ETS exposure, we found that African-American residences had significantly lower levels of particulate matter. Data from other tobacco studies indicate that particulate matter correlates well with ETS; indeed, ETS is the major contributor of indoor particulates (Cains et al. 2004
; Wallace et al. 2003
). Nevertheless, additional studies that objectively measure air nicotine are needed. Second, we did not collect information on cigarette type and thus cannot account for the potential effect of ETS exposure from mentholated cigarettes. As mentioned above, menthol has been associated with elevated levels of serum cotinine in active smokers. Finally, we grouped individuals into broad categories by race. Race is not a biologic construct, but an imprecise categorization that is a proxy for environmental, cultural, socioeconomic, and biologic differences. We need additional research to identify the specific factors that increase the risk of African-American individuals having higher levels of cotinine.
In summary, our study demonstrates that African-American children with asthma who were, on average, exposed to lower levels of ETS had higher levels of both serum and hair cotinine compared with white children with asthma. If African-American children are more susceptible to tobacco-induced toxicity, then we should target additional public policy initiatives toward reducing ETS exposure among this population. Further studies are needed to determine whether there are racial differences in the metabolism of other tobacco-related toxins and to assess the efficacy of interventions to reduce ETS exposure among all children.