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Lung

Lung refers to several types of diseases or disorders that prevent the from functioning properly. Lung disease can affect respiratory function, or the ability to breathe, and pulmonary function, which is how well lungs work. Chronic lower respiratory diseases are a set of conditions that include chronic obstructive pulmonary disease (COPD), emphysema, and chronic . Together, chronic lower respiratory diseases are a leading cause of in the United States.1 Respiratory diseases, such as COPD and , involve a narrowing or blockage of airways that reduce air flow and affect . What does NIEHS research tell us about lung In other conditions—such as pulmonary , disease? a lung scarring, and , an NIEHS conducts and funds studies to understand in which air sacs fill with fluid—the lungs have the genetic and environmental contributions to lung reduced ability to hold air. disease development, and to identify new ways to prevent and treat lung disease. Lung is a disease marked by the abnormal growth of cells. Though most starts in studies. The NIEHS-supported, the lungs, some cases start in other parts of the landmark Harvard Six Cities Study showed that body and spread to the lungs. fine-particulate air pollution contributes to excess death from lung cancer and cardiopulmonary disease What causes lung disease? in certain U.S. cities.4 As types of lung diseases vary, so do causes. Some Long-term exposure to air pollutants can increase lung diseases are caused by bacterial, viral, or fungal the chance of developing emphysema, a disease . Other lung diseases are associated usually associated with smokers.5 The findings with environmental factors, including asthma, might explain why some people who never smoked emphysema, , and lung cancer. develop lung disease. Outdoor and indoor environmental factors linked to lung disease include , radon gas, air Breathing air pollution can lead to COPD, as shown pollution, and chemicals such as , , by an NIEHS-funded study that found diesel exhaust vinyl chloride, and .2 particles, a major source of air pollution, affected genes involved in stress response in the lungs.6 Cigarette is the overall leading cause of lung cancer. Research shows that smoking just a Two large studies show an association between few cigarettes a day causes long-term lung damage, decreases in levels of air pollutants and some suggesting all levels of smoking are associated with improvement in lung function along with reductions progressive lung damage.3 Breathing secondhand in asthma symptoms.7,8 The findings underscore can also increase a person’s chance of the importance of air pollution reduction policies developing the disease. and strategies on improved air quality and .

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Genetics and lung function. By analyzing data from studies around the world, NIEHS researchers and collaborators identified more than 50 genetic changes that affect the risk of pulmonary disorders in people of European, African, Asian, and Hispanic descent. This information could affect how drugs are developed to treat lung function problems.13 at NIEHS: Cookstoves, Smoke, and Disease Globally, about 3 billion people cook daily meals using stoves fueled by wood, coal, or dung. These cooking methods produce smoke that contributes to Risk of . Respiratory syncytial an estimated 4.3 million annual , with women (RSV) is the leading global cause of lower and young children affected most. Cookstove smoke infection in infants. Researchers contributes to lung diseases such as acute pneumonia discovered mutations in a gene called in children under 5, lung cancer, , and receptor with collagenous structure, or MARCO, 9 COPD, as well as . NIEHS contributed to the severity of RSV. The findings may invested about $9 million in research related to help identify people who have a greater chance of cookstoves and their health effects, primarily in developing this disease. community-based intervention studies in Guatemala, Hexavalent chromium and lung changes. Ecuador, Nepal, Pakistan, Ghana, and the U.S. Drinking contaminated with hexavalent chromium, an industrial chemical, can lead to genetic changes in lung cells. Chromium is considered a human lung .10 Lung on a chip. NIEHS supported the development of a three-dimensional model of a breathing human lung on a microchip to test effects of environmental exposures and safety of new drugs.11

Lung cancer treatment. Non-small-cell lung cancer / Shutterstock.com Eremina Svetlana is often resistant to . Related to this type of cancer, NIEHS researchers found that silencing For more information on the a gene called INO80 led to reduced tumor growth, National Institute of Environmental Health Sciences, potentially leading to better treatment options and go to www.niehs.nih.gov. improved patient outcomes.12

1 Health, United States. 2018. U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. National Center for Health Statistics. 2 Reid PT, Innes JA. Respiratory disease. In: Walker BR, Colledge NR, Ralston SH, Penman ID, eds. Davidson's Principles and Practice of . 22nd ed. Philadelphia, PA: Churchill Livingstone; 2014:chap 19. 3 Oelsner EC, et al. 2019. Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study. Lancet Respir Med. doi: 10.1016/S2213-2600(19)30276-0. 4 Dockery, DW et al. 1993. An association between air pollution and mortality in six U.S. cities. N Engl J Med 329:1753-1759. 5 Wang M, et al. 2019. Association between long-term exposure to ambient air pollution and change in quantitatively assessed emphysema and lung function. JAMA 322(6):1-11. 6 Li X, et al. 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. 7 Berhane K, et al. 2016. Association of changes in air quality with bronchitic symptoms in children in California, 1993-2012. JAMA 315(14):1491-1501. 8 Gauderman WJ, et al. 2015. Association of improved air quality with lung development in children. N Engl J Med 372:905-913. 9 High M, et al. 2016. Determinants of host susceptibility to murine respiratory syncytial virus (RSV) disease identify a role for the innate immunity scavenger receptor MARCO gene in human infants. EBioMedicine 11:73−84. 10 Wise SS, et al. 2018. Hexavalent chromium-induced chromosome instability drives permanent and heritable numerical and structural changes and a DNA repair- deficient phenotype. Cancer Res 78(15):4203−4214. 11 Huh D, et al. 2010. Reconstituting -level lung functions on a chip. Science 328(5986):1662-1668. 12 Zhang S, et al. 2017. INO80 is required for oncogenic transcription and tumor growth in non-small cell lung cancer. Oncogene 36(10):1430-1439. 13 Wyss AB, et al. 2018. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function. Nat Commun 9(1):2976.