Urinary polyaromatic hydrocarbons are associated with adult celiac disease and kidney stones: USA NHANES, 2011–2012

Links between environmental chemicals and human health have emerged over the last few decades, but the effects from polyaromatic hydrocarbons (PAH) were less studied, compared to other commonly known environmental chemicals such as heavy metals, phthalates, arsenic, phenols, and pesticides. Therefore, it was aimed to study the relationships of urinary PAH and adult digestive conditions using a large human sample in a national and population-based study in recent years. Data was retrieved from the US National Health and Nutrition Examination Surveys, 2011–2012 including demographics, self-reported health conditions, and urinary PAH. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling, and population attributable risk (PAR) estimation. Of 5560 American adults aged 20–80 and included in the statistical analysis, urinary 4-hydroxyphenanthrene was significantly associated with celiac disease (odds ratio (OR) 1.61, 95 % confidence interval (CI) 1.14–2.26, P = 0.009). In addition, urinary 2-hydroxyfluorene (OR 1.35, 95 % CI 1.02–1.78, P = 0.038), 3-hydroxyfluorene (OR 1.35, 95 % CI 1.07–1.70, P = 0.015), 1-hydroxyphenanthrene (OR 1.48, 95 % CI 1.08–2.03, P = 0.017), 1-hydroxypyrene (OR 1.36, 95 % CI 1.05–1.77, P = 0.023), and 2-hydroxynapthalene (OR 1.25, 95 % CI 1.00–1.58, P = 0.054) were significantly associated with kidney stones, although not necessarily failing kidney. There were no statistically significant associations observed in the relationship of urinary PAH and liver problems, although higher levels of PAHs were observed. Urinary PAHs are associated with adult digestive conditions, although the causality cannot be established. From the research perspective, longitudinal monitoring from observational studies and experimental research understanding mechanism would be suggested. Regulation of minimizing PAHs exposure might need to be considered in future health and environmental policies.


Introduction
Evidence before this study Links between environmental chemicals and human health including self-rated health, hypertension, cardiovascular disease, food allergy, oral health, emotional support, and cognitive function in American adults have emerged (Shiue 2013a(Shiue , b, c, 2014(Shiue , 2015a, but the effects from polyaromatic hydrocarbons (PAHs) were less studied, compared to other commonly known environmental chemicals such as heavy metals, arsenic, phenols, and phthalates. PAHs constitute a group of chemicals that people could be exposed via vehicle exhausts, asphalt, coal tar, wild fires, agricultural burning, soil, charbroiled foods, and tobacco smoke. Approximately, everyone could be exposed to PAHs on a daily basis from multiple sources. PAH pollution may have significant health implications, and the extent of damage to organisms from PAH exposure could be dependent on several factors including degrees and types of PAH exposure (Ball and Truskewycz 2013).

Knowledge gap
Previously, animal models under a laboratory condition using rodents showed that exposure to PAHs adversely affected immunologic health (Luebke et al. 1997). However, research in this topic from a human sample has not been well conducted. Providing evidence using a human sample might help environmental health promotion in the next few years. Recently, associations of PAHs and cardiovascular, oral, emotional, and self-rated health have been observed (Shiue 2015a, b, c, d, e), but those on digestive health have not been documented. Following this context, therefore, the present study aimed to examine the relationships of urinary PAHs and adult digestive conditions using a large human sample in a national and population-based setting in recent years.

Study sample
As described elsewhere (Centers for Disease Control and Prevention 2012), US National Health and Nutrition Examination Surveys (NHANES) has been a national, populationbased, multi-year, cross-sectional study since the 1980s. Study samples are a representative sample of the civilian, noninstitutionalized US population. Information on demographics (more details via http://wwwn.cdc.gov/nchs/nhanes/2011-2012/DEMO_G.htm), serum cotinine (more details via http://wwwn.cdc.gov/nchs/nhanes/2011-2012/COTNAL_G. htm), and self-reported health conditions (more details via http://wwwn.cdc.gov/nchs/nhanes/2011-2012/MCQ_G.htm) was obtained by household interview using questionnaires. In the current analysis, the most recent study cohort in 2011-2012 with data on urinary PAHs was selected. Informed consents were obtained from participating subjects by the NHANES researchers.  Control and Prevention for analysis. According to the NHANES website (more details via http://www.cdc.gov/ nchs/data/nhanes/nhanes_11_12/PAH_G_met.pdf), the p r o c e d u r e i n v o l v e d e n z y m a t i c h y d r o l y s i s o f glucuronidated/sulfated OH-polyaromatic hydrocarbons metabolites in urine, extraction, derivatization, and analysis using isotope dilution capillary gas chromatography tandem mass spectrometry (GC-MS/MS). Ion transitions specific to each analyte and carbon-13-labeled internal standards are monitored, and the abundances of each ion are measured. Since urinary PAHs were highly skewed, they were all log transformed when performing the statistical analyses. a Adjusted for urine creatinine, age, sex, body mass index, ratio of family income to poverty, education level, serum cotinine, alcohol habit, physical activity level, and subsampling weighting

Statistical analysis
Adults aged 20 and above were included in the current statistical analysis since chronic diseases were commonly reported in adults. Associations of urinary PAHs and adult self-reported digestive conditions were examined by using t test and survey-weighted logistic regression model, presenting with mean values, odds ratios (OR), 95 % confidence intervals (CI), and P values. Covariates including urinary creatinine, age, sex, ratio of family income to poverty (proxy of socioeconomic status, calculated by dividing family (or individual) income by the poverty guidelines specific to the survey year; more details via http://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/DEMO_G.htm), body mass index, education level, serum cotinine (biomarker of smoking status), alcohol status (>12 drinks currently or not), and physical activity level (moderate recreational activity or not) were adjusted. In addition, population attributable risks from urinary PAHs, which significant associations were found, were calculated based on the formula introduced by Fleiss (1979). Statistical software STATA version 13.0 (STATA, College Station, Texas, USA) was used to perform all the analyses.

Ethics consideration
Since there are only secondary data analyses employed without any participant personal information identified by extracting statistical data from the NHANES website in the

Discussion Previous research synthesis
As mentioned earlier, literature on the effects of PAHs on human health is less than the other environmental chemicals, such as heavy metals, pesticides, arsenic, and phthalates. This is particularly apparent in the relationship of PAHs and digestive conditions. PAHs have been known as toxic chemicals and could affect renal function. Previously, PAHs were not found to be associated with renal cancer risk in Americans (Karami et al. 2011) but associated with kidney damage in Italians (Lacquaniti et al. 2012). The current findings in the present study were similar to those previous observations showing that PAHs were associated with kidney stones but not failing kidney in American adults. Animal studies using Swiss mouse and rats in vitro also presented that PAHs could damage the kidney (Krajka-Kuźniak and Baer-Dubowska 2003;Roos 2002;Bondy et al. 1995;Bowes and Ramos 1994). In other words, it is likely that PAHs could exacerbate kidney dysfunction but not necessarily lead to fatal events. One of the reasons might be that the study sample was not exposed to the exceeding toxic level. On the other hand, it was observed that people with celiac disease had higher levels of PAHs in the present study. However, no literature has addressed the potential link. Therefore, no comparison could be made and discussed.

Strengths and limitations
The present study has a few strengths. First, this study was conducted in a large and nationally representative population with mixed ethnicities and socioeconomic status. Second, this is the first time to examine the risk effects of urinary PAHs on adult digestive conditions. However, there are also a few limitations that cannot be ignored. First, there could be still other emerging chemicals from the living environments through different channels/ vehicles that we might not yet know and would need future research to further identify and examine. Second, other subtypes of disease of the digestive system were not available in the current limited dataset nor clinical measures for these specific diseases. Third, some disease events, such as celiac disease, were still suffering from small number in the statistical analysis due to the fact that it is not a very common disease. Therefore, some associations could be underestimated. Fourth, causality cannot be established in the present study due to the cross-sectional study design in nature. Future studies with a longitudinal study design to confirm or refute the current findings and, if at all, to understand the persisting risk effects along the life course from those environmental chemicals mentioned above would be suggested.

Research, practice, and policy implications
In summary, urinary PAHs were positively associated with adult celiac diseases and kidney stones. From the research perspective, longitudinal monitoring from observational studies and experimental research understanding mechanism would be suggested. From the law and human health perspectives, regulation of minimizing PAHs exposure for humans might need to be considered in future health and environmental policies and intervention programs.

Compliance with ethical standards
Conflict of interest The author declares that she has no conflicts of interest.
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Open Access This article is distributed under the terms of the Creative Comm ons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.