Air pollution linked to osteoporosis

New NIEHS-funded research showed that poor air quality was associated with higher risk factors for bone fractures and osteoporosis, especially in low-income communities. Osteoporosis is characterized by low bone mass and density.

The research included two independent, but complementary, analyses. In one, the investigators examined osteoporosis-related fracture hospital admissions among 9.2 million Medicare enrollees in the Northeast and Mid-Atlantic regions of the U.S. between 2003 and 2010. They found that a 4.18 microgram per cubic meter increase in the concentration of particulates less than 2.5 micrometers in size (PM2.5) was associated with a 4.1 percent higher rate of hospital admission for bone fracture, after adjusting for variables that might affect the fracture rate. The association between higher PM2.5 levels and increased bone fractures was evident even at PM2.5 concentrations below the 12 micrograms per cubic meter annual average limit set by the U.S. Environmental Protection Agency. The association was also stronger in communities with lower incomes.

A concurrent analysis examined data from eight years of follow-up among 692 middle-aged, low-income adults in the Boston Area Community Health–Bone Survey group. This analysis showed that participants living in areas with higher levels of PM2.5 and black carbon, which comes from automotive emissions, had lower levels of a hormone that is key for controlling calcium levels in bones. The researchers also found that for each 0.106 microgram per square meter increase in one-year black carbon concentration, participants had a 0.08 percent per year decrease in neck bone mineral density and 0.06 percent per year decrease in radius bone mineral density.

Citation: Prada D, Zhong J, Colicino E, Zanobetti A, Schwartz J, Dagincourt N, Fang SC, Kloog I , Zmuda JM, Holick M, Herrera LA, Hou L, Dominici F, Bartali B, Baccarelli AA. 2017. Association of air particulate pollution with bone loss over time and bone fracture risk: analysis of data from two independent studies. Lancet Planet Health 1(8):e337−e347.

New tumor-promoting pathway for liver cancer discovered

A new study from NIEHS grantees showed that chronic liver inflammation can promote cancer by suppressing one of the body’s natural mechanisms to fight cancer development. The discovery of this new tumor-promoting pathway could lead to new liver cancer treatments.

The researchers studied a new mouse model of liver cancer that more closely mimics the way that human liver cancer develops. In these mice, tumors develop as a natural consequence of nonalcoholic steatohepatitis (NASH), a chronic metabolic disorder that causes liver damage, fibrosis, and cell mutations.

The researchers found that mutations associated with NASH provoke cytotoxic T cells to recognize and attack newly emerging cancer cells. However, chronic liver inflammation led to the accumulation of another type of immune cell known as immunosuppressive lymphocytes. The experiments showed that immunosuppressive lymphocytes use a molecule known as PD-L1 to interfere with cytotoxic T cells, leading to liver tumors in the chronically inflamed mice. In mice lacking tumor-fighting cytotoxic T cells, 27 percent of 15 mice had large liver tumors at six months. However, mice of the same age that retained their cytotoxic T cells had no tumors. Similarly, mice without immunosuppressive lymphocytes had almost no tumors even at 11 months, most likely because cytotoxic T cells could fight the emerging cancer.

The results could help scientists develop new ways to interfere with immunosuppressive lymphocytes to prevent or treat early liver cancer.

Citation: Shalapour S, Lin XJ, Bastian IN, Brain J, Burt AD, Aksenov AA, Vrbanac AF, Li W, Perkins A, Matsutani T, Zhong Z, Dhar D, Navas-Molina JA, Xu J, Loomba R, Downes M, Yu RT, Evans RM, Dorrestein PC, Knight R, Benner C, Anstee QM, Karin M. 2017. Inflammation-induced IgA plus cells dismantle anti-liver cancer immunity. Nature 551(7680):340–345. (Story)

Lead exposure in African-Americans begins before birth

Results from a new NIEHS-supported study revealed that African-American children may experience higher prenatal and early childhood lead levels than white children. The results suggest that testing women for lead during or before pregnancy may help identify risk of lead exposure to their children, particularly for African-American women.

The study included pregnant women living in and around Detroit, Michigan who were recruited into the Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study birth cohort. The researchers analyzed baby teeth from the study participants’ children born between September 2003 and December 2007. High-resolution mapping of the growth rings in baby teeth can reveal the intensity and timing of exposure during different developmental periods. The study included exposure data from the baby teeth of 122 children, 71 of whom were African-American and 51 of whom were white.

The researchers found that African-American children experienced 2.2 times higher lead levels in the second and third trimesters and 1.9 times higher lead levels during their first year of life compared with white children.

African-American children have the highest occurrence of elevated blood lead levels in the U.S. Based on the new findings, the researchers concluded that this disproportionate burden of lead exposure begins in the womb and persists into early childhood.

Citation: Cassidy-Bushrow AE, Sitarik AR, Havstad S, Park SK, Bielak LF, Austin C, Johnson CC, Arora M. 2017. Burden of higher lead exposure in African-Americans starts in utero and persists into childhood. Environ Int 108:221–227.

How particulate matter aggravates COPD

NIEHS grantees have uncovered the key molecular pathway involved in chronic obstructive pulmonary disease (COPD) induced by air pollution exposure. Although cigarette smoke is the most common irritant that causes COPD, at least one-fourth of people with COPD are nonsmokers and thus could have COPD linked to air pollution.

In the new study, the researchers investigated gene expression changes in mouse models with lesions similar to those induced by air pollution and in human bronchial epithelial cells after exposure to diesel exhaust particles. They found that diesel exhaust particles, a major source of particulate matter (PM) air pollution, reduced genes expression for mitochondrial complexes I and V, and induced COPD-like symptoms in the mice. Treatment with taurine and 3-methyladenine completely restored mitochondrial gene expression levels and protected both the cells and animals from PM-induced COPD. This potential therapeutic intervention likely helped reduce harmful effects of inflammation, including mitochondrial oxidative stress and intracellular degradation.

The researchers also identified 1-nitropyrene as a major toxic component of diesel exhaust particles involved in PM-induced COPD. In addition, they observed that, compared with people with normal lung function, COPD patients were more susceptible to PM because of an increased inflammatory response.

Citation: Li X, Yang H, Sun H, Lu R, Zhang C, Gao N, Meng Q, Wu S, Wang S, Aschner M, Wu J, Tang B, Gu A, Kay SA, Chen R. 2017. Taurine ameliorates particulate matter-induced emphysema by switching on mitochondrial NADH dehydrogenase genes. Proc Natl Acad Sci U S A 114(45):E9655–E9664.