Growing evidence shows that exposure to lead in the environment is associated with cardiovascular disease, including increased risk of hypertension. However, those studies have looked at lead concentrations in blood, not bone lead, a better indicator of cumulative lead exposure over time. In a new study, researchers at the Harvard School of Public Health (HSPH) and the University of Michigan School of Public Health found that bone lead was associated with a higher risk of death from all causes, particularly from cardiovascular disease. It is the first study to analyze the association between bone lead and mortality.

The study appears online on September 8, 2009, on the website of the journal Circulation and will appear in a later print edition. 

“The findings with bone lead are dramatic. It is the first time we have had a biomarker of cumulative exposure to lead and the strong findings suggest that, even in an era when current exposures are low, past exposures to lead represent an important predictor of cardiovascular death, with important public health implications worldwide,” said Marc Weisskopf, assistant professor of environmental and occupational epidemiology at HSPH and lead author of the study.

Air pollution was the main source of lead in the environment in recent years, though it has been decreasing since leaded gasoline was banned in the U.S. in the mid-1990s. Most of the lead circulating in the body is deposited in bone and remains there for years, unlike blood lead, which has a half life of about 30 days. Since adverse effects from lead on the cardiovascular system would be expected to show up over time, the researchers expected that bone lead would be a better marker of chronic toxicity.

The researchers, led by Weisskopf and senior author Howard Hu, professor of environmental health, epidemiology and internal medicine at the University of Michigan School of Public Health, analyzed data from 868 participants in the Department of Veterans Affairs Normative Aging Study, a study of aging in men that began in 1963. Blood lead and bone lead—analyzed using X-ray fluorescence—were measured for each of the participants. The results showed that the risk of death from cardiovascular disease was almost six times higher in men with the highest levels of bone lead compared to men with the lowest levels. The risk of death from all causes was 2.5 times higher in men with the highest levels of lead compared to those with the lowest levels. The results appeared independent of age, smoking, education, race, alcohol, physical activity, BMI, high density lipoprotein or total cholesterol levels, hypertension or diabetes.

There are a number of mechanisms, such as increased oxidative stress, by which lead exposure may result in cardiovascular mortality, say the authors. They also note that, in addition to high blood pressure, exposure to lead has been associated with widened pulse-pressure (an indicator of arterial stiffening) and heart disease.

Given that bone lead may be a better biomarker of cumulative lead exposure than blood lead, it may be the best predictor of chronic disease from exposure to lead in the environment. “In addition to spurring further public health measures to reduce exposure to lead and to begin monitoring for cumulative exposure, mechanistic and clinical research is needed to determine if opportunities exist to conduct targeted screening and treatment that can further reduce the burden of cardiovascular disease for the millions of adults who have had years of elevated lead exposure in the past,” said Hu.

Reference:    Harvard School of Public Health, Lead in bone associated with increased risk of death from cardiovascular disease in men, Boston, MA, September 9, 2009

The study described was initiated by the Israel Ministry of Health as an effort to respond to and deal with public concern about possible health disorders related to odorous emissions (composed of a great many of organic and inorganic chemicals) from the regional industrial park (IP) in the Negev, southern Israel. Previous ecological studies found that adverse health effects in the Negev Bedouin population were associated with residential proximity to the IP. The objective of the current study was to investigate a hypothesis concerning the link between the IP proximity and life prevalence (LP) of upper respiratory tract chronic diseases (URTCD) and asthma in children aged 0-14 years living in rural Negev, Israel, in small agricultural communities.  

The cross-sectional study was conducted in 7 localities simultaneously during 2002. The following indirect exposure indicators were used: (1) distance (less than 20 km/ more than 20 km) from the IP (‘distance’); (2) presence (yes/no) of the dominant wind direction being from the IP toward a child’s locality (‘wind direction’); and (3) the child’s mother having made odour complaints (yes/no) related to the IP (‘odour complaints’). A 20 km cut-off point was used for ‘distance’ dichotomization as derived from the maximum range of ‘odour complaints’. This gave 3 proximal and 4 distant localities, and division of these by the ‘wind direction’ gave one versus two localities. The study population consisted of 550 children born in the localities. Medical diagnoses were collected from local clinic records. The following were included in the interviewer-administered questionnaire for a child’s parents: (1) demography (the child’s birth date, gender, mother being married or not, parental origin and education, number of siblings); (2) the child’s birth history (pregnancy and delivery) and breast-feeding duration; (3) the child’s parental respiratory health; and (4) environmental factors (parental smoking and occupational hazardous exposure, domestic use of pesticides, domestic animals, outdoor odour related to the IP emissions). For statistical analysis, Pearson’s chi(2), t-tests and multivariate logistic regressions were used, as well as adjusted odds ratios (OR) within a 95% confidence interval.  

The multivariate analysis showed that increased LP of URTCD in children of proximal localities was statistically significant when associated with odour complaints (OR = 3.76 [1.16, 12.23]). In proximal localities, LP of URTCD was higher (at borderline level statistical insignificance p = 0.06) than in distant localities (OR = 2.31 [0.96, 5.55]). The following factors were found to be related to the excess of the LP of URTCD: (1) father’s lower education (by distance: OR = 2.62 [1.23, 5.57]; by wind direction: OR = 4.07 [1.65, 10.03]); (2) in-vitro fertilization (by distance: OR = 3.03 [1.17, 7.87]; by wind direction: OR = 4.34 [1.48, 12.72]). In proximal localities, the increase in asthma LP was associated with: (1) wind direction (OR = 1.95 [1.01, 3.76]); (2) a child’s male gender (OR = 2.95 [1.48, 5.87]); and (3) a child’s mother’s having had an acute infectious disease during pregnancy (OR = 4.84 [1.33, 17.63]).  

An increased LP of chronic respiratory morbidity among children living in small agricultural localities in the Negev was found to be associated with indirect measurements of exposure (distance, wind direction and odour complaints) to IP emissions. These results, in conjunction with previously reported findings in the Negev Bedouin population, indicate a need for environmental protection measures, and monitoring of air pollution and the health of the rural population. 

Reference: Karakis I, Kordysh E, Lahav T, Bolotin A, Glazer Y, Vardi H, Belmaker I, Sarov B., Life prevalence of upper respiratory tract diseases and asthma among children residing in rural area near a regional industrial park: cross-sectional study, School of Public Health, University of Haifa, Haifa, Israel. Rural Remote Health. 2009 Jul-Sep;9(3):1092 

The same mechanism that helps you detect bad-tasting and potentially poisonous foods may also play a role in protecting your airway from harmful substances, according to a study by scientists at the University of Iowa Roy J. and Lucille A. Carver College of Medicine. The findings could help explain why injured lungs are susceptible to further damage.  

The study, published online July 23 in Science Express, shows that receptors for bitter compounds that are found in taste buds on the tongue also are found in hair-like protrusions on airway cells. In addition, the scientists showed that, unlike taste cells on the tongue, these airway cells do not need help from the nervous system to translate detection of bitter taste into an action that expels the harmful substance. 

The hair-like protrusions, called motile cilia, were already known to beat in a wave-like motion to sweep away mucus, bacteria and other foreign particles from the lungs. 

The study is the first to show that motile cilia on airway cells not only have this “clearing” function, but also use the receptors to play a sensory role. The researchers also found that when the receptors detect bitter compounds, the cilia beat faster, suggesting that the sensing and the motion capabilities of these cellular structures are linked. 

“On the tongue, bitter substances trigger taste cells to stimulate neurons, which then evoke a response — the perception of a bitter taste. In contrast, the airway cells appear to use a different mechanism that does not require nerves,” said Alok Shah, a UI graduate student and co-first author of the study. “In the airways, bitter substances both activate the receptors and elicit a response — the increased beating of the cilia — designed to eliminate the offending material.”

Shah and co-first author Yehuda Ben-Shahar, Ph.D., an assistant professor of biology at Washington University who was a postdoctoral fellow at the UI when the study was conducted, worked in the lab of senior study author Michael Welsh, M.D. (photo, upper left), UI professor of internal medicine and molecular physiology and biophysics, who holds the Roy J. Carver Chair of Internal Medicine and Physiology and Biophysics. Welsh also is a Howard Hughes Medical Institute investigator. 

“These findings suggest that we have evolved sophisticated mechanisms to guard ourselves from harmful environmental stimuli,” Ben-Shahar said. “Our work also suggests that losing cilia in the lungs, due to smoking or disease, would result in a reduced general ability to detect harmful inhaled chemicals, increasing the likelihood of further damaging an injured lung.”

In addition to Ben-Shahar, Shah and Welsh, the UI team included Thomas Moninger, assistant director of the UI Central Microscopy Research Facility, and Joel Kline, M.D., UI professor of internal medicine. 

The study was funded by grants from the National Institutes of Health. 

Reference:   University of Iowa, Airway cells use ‘tasting’ mechanism to detect and clear harmful substances, July 24, 2009

CO Exposure could make them more vulnerable to disease

A UCLA study has discovered that chronic exposure during pregnancy to miniscule levels of carbon monoxide damages the cells of the fetal brain, resulting in permanent impairment. The journal BMC (BioMed Central ) Neuroscience published the findings June 22 in its online edition.

“We expected the placenta to protect fetuses from the mother’s exposure to tiny amounts of carbon monoxide,” said John Edmond, professor emeritus of biological chemistry at the David Geffen School of Medicine at UCLA. “But we found that not to be the case.”

The researchers exposed pregnant rats to 25 parts per million carbon monoxide in the air, an exposure level established as safe by Cal/OSHA, California’s division of occupational health and safety.

Dr. Ivan Lopez, UCLA associate professor of head and neck surgery, tested the rats litters 20 days after birth. Rats born to animals who had inhaled the gas suffered chronic oxidative stress, a harmful condition caused by an excess of harmful free radicals or insufficient antioxidants.

“Oxidative stress damaged the baby rats brain cells, leading to a drop in proteins essential for proper function,” said Lopez. “Oxidative stress is a risk factor linked to many disorders, including autism, cancer, Alzheimer’s, Parkinson’s, Lou Gehrig’s disease, multiple sclerosis and cardiovascular disease. We know that it exacerbates disease.”

“We believe that the minute levels of carbon monoxide in the mother rats environment made their offspring more vulnerable to illness,” added Edmond. “Our findings highlight the need for policy makers to tighten their regulation of carbon monoxide.”

Tobacco smoke, gas heaters, stoves and ovens all emit carbon monoxide, which can rise to high concentrations in well-insulated homes. Infants and children are particularly vulnerable to carbon monoxide exposure because they spend a great deal of time in the home.

No policies exist to regulate the gas in the home. Most commercial home monitors sound an alarm only hours after concentrations reaches 70 parts per million – nearly three times the 25 parts per million limit set by Cal/OSHA.

A grant from the University of California’s Tobacco-related Disease Research Program supported the research.

Reference: Elaine Schmidt, UCLA study reveals how tiny levels of carbon monoxide damage fetal brains, UCLA, 6/25/2009

The authors investigated the association of early-life exposure to indoor air pollution with neuropsychological development in preschoolers and assessed whether this association differs by glutathione-S-transferase gene (GSTP1) polymorphisms. A prospective, population-based birth cohort was set up in Menorca, Spain, in 1997-1999 (n = 482).

Children were assessed for cognitive functioning (McCarthy Scales of Children’s Abilities) and attention-hyperactivity behaviors (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) at age 4 years.

During the first 3 months of life, information about gas appliances at home and indoor nitrogen dioxide concentration was collected at each participant’s home (n = 398, 83%). Genotyping was conducted for the GSTP1 coding variant Ile105Val. Use of gas appliances was inversely associated with cognitive outcomes (beta coefficient for general cognition = -5.10, 95% confidence interval (CI): -9.92, -0.28; odds ratio for inattention symptoms = 3.59, 95% CI: 1.14, 11.33), independent of social class and other confounders.

Nitrogen dioxide concentrations were associated with cognitive function (a decrease of 0.27 point per 1 ppb, 95% CI: -0.48, -0.07) and inattention symptoms (odds ratio = 1.06, 95% CI: 1.01, 1.12).

The deleterious effect of indoor pollution from gas appliances on neuropsychological outcomes was stronger in children with the GSTP1 Val-105 allele. Early-life exposure to air pollution from indoor gas appliances may be negatively associated with neuropsychological development through the first 4 years of life, particularly among genetically susceptible children.

Reference: Morales E, Julvez J, Torrent M, de Cid R, Guxens M, Bustamante M, Künzli N, Sunyer J., Association of early-life exposure to household gas appliances and indoor nitrogen dioxide with cognition and attention behavior in preschoolers, Center for Research in Environmental Epidemiology, Barcelona, Catalonia, Spain, Am J Epidemiol. 2009 Jun 1;169(11):1327-36.