This documents contain narrative about the Lead and 4 articles summaries, would you please help edit the language?

Lead

                Lead is criteria pollutant that usually people encounter with through many exposure pathways. Leaded gasoline is considered as the single major contributor to human exposure accounting for 95% of all exposure in the entire history. Fortunately, leaded gasoline was banned in 1986. Another significant exposure pathway is the Pb-containing paint chips or dusts from floor or soils. This pathway is of a great concern in older buildings especially for children as they have a high rate of hand-to-mouth activity. Tap water is a major source of exposure nowadays as all water pipes contain lead that might leach and contaminate water under specific set of conditions as in the crisis of Flint, Michigan.

Wide range of adverse health effects are attributable to lead exposure. Lead has multisystem effect, it leads to hematopoietic, central nervous and nephrotic toxicity. The target organ of lead is the bone which has the highest body burden of lead and where it stored for decades, whereas the critical organ is the brain which shows the most adverse health effect in case of exposure. The toxicity of lead is exerted by many mechanisms: mimicking calcium and substituting it in essential cellular functions, perturbing kidney functions leading to decrease in glomerular filtration rate, affecting neurotransmitters in the nervous system leading to cognitive impairments and affecting heme-synthesis pathway by perturbing ferrochelatase enzyme leading to anemia.

Children are more vulnerable to lead exposure as they have higher rate of hand-to-mouth activity as well as higher rate of lead absorption (42%) and retention (68%). Moreover, their neural pathways are being developed and any damage to theses pathways is irreversible.

Lead is regulated as a criteria pollutant under the National Ambient Air Quality Standards (NAAQS) which was established by the Environmental Protection Agency (EPA) as mandated by the Clean Air Act (CAA). NAAQS regulated pollutants using health-based standards in which the cost is not considered in the regulation. Additionally, Safe Drinking Water Act might have a role in regulating contaminants level -including lead- in public drinking water supplies. Banning leaded gasoline tremendously minimized human exposure. The current EPA blood lead level is 5ug/g, however, scientists believe that there is no threshold safe level.

Lead exposure mitigation is limited by the abundance lead pipes either in public service lines and in homes which make it difficult to take representative samples. Although corrosion control should be maintained by law, many factors can contribute to increasing corrosivity of lead from water pipes such as increase in acidity of water and change the water supply source. Another limiting factor is the cost of replacing these pipes as well as for water testing, it is pretty expensive. In the same time, the population that most probably to have lead pipes are the poorest. Moreover, lack of lead pipes map in the public service line and difficult to control the hand-to-mouth activity in children. Effective risk communication should address all the limitations. More testing for blood lead level is needed as well as map showing locations of lead pipes.

 

 

 

 

Cumulative Exposure to Lead in Relation to Cognitive Function in Older Women

This paper addressed the impact of cumulative community-level exposure to lead in the cognitive functions of older women. Although lead exposure effect on cognitive functions has been barely studied during the past ten years, women are underrepresented in most of the studies. For instance, the author identified 16 out of 21 articles in the literature in which women constitute only 20% of the studies participants.

They hypothesized that there is an inverse association between chronic low-dose exposure to lead and cognitive function test score in older women.  Another hypothesis was that this relationship is even stronger for the lead level in the bone.

There were 587 women enrolled in this study who met the eligibility criteria. A women participant is considered eligible if she lived in greater Boston, Massachusetts, metropolitan area; did not report a past medical history of a major chronic disease and her body mass index is not ≥ 29. After That, a participant was categorized as a case if she diagnosed with hypertension anytime from 1990 to 1994 or otherwise she will be categorized as a control.

The authors tested their two hypotheses by obtained blood lead level that represent recent and historical exposure to lead. Additionally, they measured bone lead level in mid-tibial shaft and patella to estimate the cumulative exposure over last years using K-X-ray fluorescence. Five years later, trained nurses assessed the cognitive functions of the study participants using validated telephone interviews. The assessment consisted of testing to different cognitive functions such as orientation and memory and the score of 31 was considered as the cutoff score below which a participant considered cognitively impaired.

Then data were analyzed, each biomarker was separately assessed for its association with cognitive performance. during analysis, many confounders were taking into account such as age, education, lifestyle, socioeconomic status, vascular and mental health factors.

The average lead level in tibia was 10.5 µg/g, while in patella was 12.6 µg/g and in blood was 2.9 µg/dL showing that all mothers were below the EPA safe level of 5 µg/dL. A Higher level of lead in all the three biomarkers was associated with worse cognitive performance. Tibia bone lead level was the only statistically significant biomarker which suggested that historical exposure to lead have more impact on cognition than recent exposure. This study suggested possible adverse effects on cognitive performance in older age due to cumulative low-level exposure to lead.

The authors controlled for many sources of uncertainty that might affect the result of this study. This Telephone-based survey may introduce interviewer bias and limits the author's' ability to test the effect of lead exposure on visuospatial ability. Moreover, blood lead level reflects recent exposure and does not reflect the effect of cumulative exposure. The unexpected result of better fluency test was associated with higher BLL from patella bone samples is another source of uncertainty. Selection bias might be introduced as a large proportion of the participants are recruited from another hypertension study.

 

 

 

Association of Cumulative Lead Exposure with Parkinson’s Disease

The association between chronic exposure to lead and Parkinson’s Disease (PD)

is understudied in the literature. The only published study used Bone Lead Level (BLL) as a biomarker in this regard found no significant correlation. Moreover, many previous studies were dependent on self-reported exposure to lead. As proved by experiments, lead is an endocrine disruptor that affects dopamine synthesis and can potentially result in PD. this study was designed to address the possible correlation between cumulative exposure to lead and PD.

The authors hypothesized that chronic exposure to lead might be correlated with higher risk of developing PD. in order to test this hypothesis, a case-control study design was used in which bone samples were collected from 330 patients with PD as cases and 308 participants not having the disease as controls. The cases were recruited from four different healthcare settings in the city of Boston, MA as well as from normative aging study participants. On the other hand, cases’ family members , friends, and others were recruited as controls if they met some proposed requirements to ensure comparability. Bone samples were taken from midshaft tibia and patella that represent cortical and trabecular bone types, respectively. These two types of bones differ in the rate of turnover in which trabecular type has a higher rate which helps in predicting the time frame of exposure. KXRF instrument was used to measure BLL. after that, statistical testings were ran using logistic regression after adjustment was done to the odds ratio of PD.

The average BLL in tibia found to be 15.9 (standard deviation, 12. 1) μg/g, whereas in patella found to be 13.6 (standard deviation, 10. 7) μg/g. Additionally, a significantly higher odd ratio was found in participants in the highest quartile of tibia BLL than those in the lowest quartile. To conclude, this study suggested a positive association between cumulative lead exposure as indicated by tibia bone and a higher risk of developing PD. However, there was no association found with patella bone BLL. These findings attributed PD to previous decades exposure to lead.

The authors accounted for many potential confounding factors such as running the analysis using different subgroups within cases and/ or controls. On the other hand, there were some potential confounders that they could not control for such as specification of recruitment rate of study participants by researchers, recruiting participants who already have the outcome of interest, PD, which make it difficult to infer temporality. Moreover, not recruiting cases from community advertisement and Harvard Cooperative Program on Aging (HCPOA). However, the significance of association persisted after excluding them from the analysis.

 

 

 

 

 

 

 

 

 

Bone Lead and Blood Lead Levels in Relation to Baseline Blood Pressure and the Prospective Development of Hypertension

This paper addressed the relationship between cumulative community-level exposure to lead and blood pressure. Many studies have reviewed this subject recently and proposed a possible slight rise in blood pressure associated with increased Blood Lead Level (BLL), and yet the causal association is still debatable. Previous studies used BLL as a biomarker which inaccurately reflects the actual cumulative exposure. In contrary, this study used both blood and bone lead level.

Researchers usually chose to measure bone lead level in tibia and patella as they represent two different type of bones in term of the rate of turnover. Tibia is made of cortical bone, whereas patella is made of trabecular bone which has a higher rate of turnover.

The hypothesis that they tested was cumulative community-level exposure to lead is probably associated with increased risk of hypertension. In order to test this hypothesis, the authors recruited study participants who were middle-aged to elderly men from the Normative Aging Study. The required data were completely obtained from 840 participants out of whom seven were excluded. The data collected were bone lead measurements from mid-tibial shaft and patella using K-shell X-ray Fluorescence (KXRF) instruments, BLL by analyzing blood sample using Graphite Furnace Atomic Absorption Spectroscopy (GFAAS), blood pressure using mercury sphygmomanometer. Other data collected to account for potential confounders included biographical data, past medical history, family history of hypertension, dietary calcium and sodium intake, educational level, smoking and alcohol consumption. Then, 337, 182 and 314 participants were categorized as normotensive, borderline and hypertensive respectively.

                The overall BLL found to be low between <1 - 35 ug/dl which represent the exposure level found in regular American population in the same age group. There was no statistically significant difference between eligible participant and non-eligible or excluded participants with regard to potential confounders data. The bone lead level in a participant with no reported history of hypertension and normal blood pressure measurements during enrollment found to be directly correlated with increased blood pressure both at baseline and during follow-up after controlling for confounding factors. Tibia lead level was correlated more with systolic blood pressure, while patella lead level was correlated more with hypertension. They potential confounders they accounted for in the statistical model include having baseline increase of blood pressure, history of diagnosed hypertension, age, body mass index and other factors. Selection bias is improbable as study participants who had and had not provided bone sample had similar bone lead and blood pressure measurements.

 

 

 

 

 

 

 

Cumulative Lead Exposure and Prospective Change in Cognition among Elderly Men

                This article addressed the impairment of cognitive function that chronic exposure to lead in low and commonly encountered doses might lead to among older men. This area of science has not been well studied and the increasing in the number of elderly population in our nation raise a significant concern regarding this potential health effects.

They hypothesized that chronic and cumulative exposure to lead in low doses is associated with cognitive function impairment in older men. In order to test this hypothesis, 466 male participants aged 67.4 on average out of 753 were recruited from Normative Aging Study (NAS) and completed Mini-Mental State Examination (MMSE). K-shell X-Ray Fluorescence (KXRF) measurements of Bone Lead Level (BLL) from tibia and patella bone samples as well as blood samples to measure lead level in the circulatory system were obtained. These were used as surrogate markers to estimate the body burden of lead exposure. To evaluate the cognitive functions, MMSE were conducted twice with 3.5 years on average in between and then the change in the score was calculated. After that, they excluded participants with high uncertainty in the measurements and extreme outliers. Then, statistical analyses were run to examine the significance of the association between variables after controlling for potential confounders.

Smokers, older men, less educated tend to have higher lead measurements. The higher the lead level, the more impaired the cognitive functions. The association was more robust and strong with BLL from patella bone measurements, whereas it was weak with tibia bone measurements. On the other hand, there was no significant association found between blood lead level and MMSE score. These findings were relatively consistent after excluding potential confounders such as outliers and participants with missing information. In conclusion, community-level exposure to lead results in higher BLL which is associated with a decrement in cognitive functions in older men.

                There were many limitations and uncertainty to this study that the authors did not control for. The confounders that they adjusted for might affect the MMSE score. Additionally, they were unable to obtain BLL from 27% of the participants and unable to conduct the second MMSE to 38% of participants. Survivor effect might have a role in this result as the more vulnerable subjects may already pass away leading to underestimation of the lead exposure effect.