Environmental tobacco smoke and newborn lung development
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Environmental tobacco smoke (ETS) is defined as the combination of sidestream smoke released from the burning end of a cigarette and that portion of mainstream smoke exhaled by smokers. Health effects associated with exposure to ETS have been clearly demonstrated, but still remain somewhat controversial. In 1993 the U.S. Environmental Protection Agency declared environmental tobacco smoke (ETS) to be a human carcinogen that kills approximately 3,000 nonsmokers a year. Young children are also affected by ETS exposure with increases in the incidence of pneumonia, bronchitis, and middle ear infection. For children with asthma, ETS exposure increases the severity and frequency of asthmatic attacks. However, the cause(s) for greater and more adverse health risks associated with ETS exposure in children compared with adults is (are) unknown. 
 
 
 
 
 
 We propose to study in our laboratory the effects of exposure to ETS on the maturation and function of the lung airways during fetal and early postnatal development in rats. This species is ideal to study due to its rapid fetal and postnatal growth to adulthood over a period of approximately 70 days. We have found that ETS exposure during the fetal and early postnatal periods is associated with a significant increase in lung airway narrowing, similar to that seen in asthmatic children. Also associated with these hyperactive airways is a dramatic increase in pulmonary neuroendocrine cells (PNECs), which compose a small fraction of the cells lining the lung airways. The function of PNECs is unknown; however, they are thought to be important in the pulmonary response to substances that are inhaled into the lungs and help to regulate airway tone and function. 
 
 
 
 
 
 It is our hypothesis that PNECs may be directly responsible for increased airway responsiveness (such as that seen in asthma) by either releasing bronchoconstrictive mediators or by increasing the mass of airway smooth muscle through smooth muscle cell proliferation. We propose to test this hypothesis in rats using environmental tobacco smoke (ETS) with exposure occurring during critical periods of lung growth and development from fetal to early adulthood in the rat. An important observation from our laboratory has been that when rats are exposed to ETS in utero (via the mother) followed by direct exposure for the first 3 weeks of life, their lungs remain markedly hyperresponsive when measured at 8 weeks of age, despite the absence of ETS exposure for the preceding 5 weeks. The discovery of this change in the lungs due to smoke exposure in newborn rats is highly analogous to the development of childhood asthma in humans. This animal model affords us the opportunity to examine whether there is a critical period during lung development when exposure to ETS leads to increased airway hyperresponsiveness and whether changes in airway PNEC number and/or function might be responsible for these observed changes.