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Extramural Papers of the Month

March 2009

Clean Air Extends Life Expectancy

New NIEHS-supported research findings published in the New England Journal of Medicine suggest that improvements in air quality have increased average life expectancy in the U.S. by approximately five months. The researchers tracked particulate matter air pollution in 51 major metropolitan areas from 1978 through 2001 and compared those data to death records and census data. On average, life expectancy increased by 2.72 years with about 15 percent of that increase due to improved air quality. Cities that had the greatest air quality improvements saw the greatest gains in life expectancy. Overall, a reduction of 10 micrograms per cubic meter in the ambient air concentration of particulate matter was associated with an estimated increase in average life expectancy of 0.61 years.

The study signals that efforts to curtail the small, toxic particles known as PM2.5 produced by power plants, factories, cars, and trucks and inhaled by city-dwellers had significant health benefits over those two decades. Clean-air advocates and public health specialists have touted the findings and have said that even stronger standards for air pollutants are needed and justified.

Research over the past few decades, much of which has been particulate matter air pollution, has found that the foreign matter inflames lung tissue and increases the plaque that forms in arteries, contributing to heart and lung disease.

Citation: Pope CA 3rd, Ezzati M, Dockery DW ( Exit NIEHS. 2009. Fine-particulate air pollution and life expectancy in the United States. N Engl J Med 360(4):376-386.

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Variations in Human Gut Microbiome Linked to Obesity

A study partially funded by NIEHS and published in the journal Nature has found that the gut microbial population in humans is unique to each individual with substantial differences between obese and lean people. The researchers analyzed the gut microbiomes of lean and obese, fraternal and identical female twins and their mothers. They found that the collection of bacteria is similar in related individuals, but not identical. The study participants are part of a long-standing study of Missouri-born twins designed to decipher the influence of the environment versus genetics on many aspects of human health.

Peter Turnbaugh, lead author of the study, sequenced the microbial DNA of a subset of obese and lean twin pairs. He found that the obese individuals had an increase in nearly 300 bacterial genes primarily responsible for extracting calories from food and processing nutrients. These findings support earlier work in mice that established a connection between obesity and energy harvested from the diet by gut bacteria.

Family members were more likely to harbor similar communities of bacteria; however the degree of similarity was the same for identical and fraternal twins regardless of whether they lived together or in different regions of the U.S. This finding suggests that early environmental exposures play a key role in determining which bacteria colonize our intestinal tracts.

Citation: Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI ( Exit NIEHS. 2009. A core gut microbiome in obese and lean twins. Nature 457(7228):480-484.

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MicroRNAs Modulate Smoking Damage

A multidisciplinary study conducted at Boston University identified 28 microRNAs that are differentially expressed in bronchial airway epithelial cells from smokers compared to non-smokers. These microRNAs regulate gene expression changes occurring in people who smoke and who get smoking-related diseases, according to the study's senior author Avrum Spira, M.D.

The investigators harvested samples of cells from 10 smokers and 10 non-smokers. The majority of the microRNAs were down-regulated in smokers - suggesting that restoration of expression to more normal levels could protect smokers from smoking-related diseases, such as emphysema and lung cancer. Mir-218 was identified as a key microRNA for controlling a group of genes involved in protection of lung tissues from oxidative damage.

The investigators speculate that mir-218 is crucial in preventing lung injury and thus the potential development of lung disease. Mir-218 activity could also be used as a marker for lung injury and might be useful in predicting which people are more likely to develop lung diseases as a result of smoking.

Citation: Schembri F, Sridhar S, Perdomo C, Gustafson AM, Zhang X, Ergun A, Lu J, Liu G, Zhang X, Bowers J, Vaziri C, Ott K, Sensinger K, Collins JJ, Brody JS, Getts R, Lenburg ME, Spira A ( Exit NIEHS. 2009. MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci U S A 106(7):2319-2324.

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New Treatment Found for Ozone-Caused Wheezing

A collaborative team of researchers at NIEHS and Duke University has discovered a cause of airway inflammation and irritation in response to breathing ozone, a common air urban air pollutant. Ozone exposure causes constriction of breathing passages making normal respiration much more difficult. This is a dangerous condition in people with breathing abnormalities, such as chronic obstructive pulmonary disease and asthma.

Using an animal model, the research team found increased amounts of a sugar known as hyaluronan and found the compound to be directly responsible for the airway constriction and irritation. The researchers think hyaluronan may also contribute to asthma symptoms in humans.

Adding to the importance of this work, the researchers identified several proteins that can alter the hyaluronan effect and that might be useful treatments for asthma. They were able to block the hyaluronan effect by administering a natural protein that binds to hyaluronan and thus prevents it from causing the airway irritation. The researchers conclude that pharmacologic modification of hyaluronan is a potential strategy for treatment of reactive airway disease.

The senior author of the study, John Hollingsworth, M.D., is a recipient of an Outstanding New Environmental Scientist award from NIEHS.

Citation: Garantziotis S, Li Z, Potts EN, Kimata K, Zhuo L, Morgan DL, Savani RC, Noble PW, Foster WM, Schwartz DA, Hollingsworth JW ( Exit NIEHS. 2009. Hyaluronan mediates ozone-induced airway hyperresponsiveness in mice. J Biol Chem [Epub ahead of print]. [Story] (

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March 2009 Cover Page

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