Mouse Lung Structure and Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change Modeling

Abstract

BACKGROUND: Climate change models predict that atmospheric carbon dioxide [CO 2 ] levels will be between 700 and 900 ppm within the next 80 y. Despite this, the direct physiological effects of exposure to slightly elevated atmospheric CO 2 (as compared with ∼ 410 ppm experienced today), especially when exposures extend from preconception to adulthood, have not been thoroughly studied. OBJECTIVES: In this study we aimed to assess the respiratory structure and function effects of long-term exposure to 890 ppm CO 2 from preconception to adulthood using a mouse model. METHODS: We exposed mice to CO 2 ( ∼ 890 ppm) from prepregnancy, through the in utero and early life periods, until 3 months of age, at which point we assessed respiratory function using the forced oscillation technique, and lung structure. RESULTS: CO 2 exposure resulted in a range of respiratory impairments, particularly in female mice, including higher tissue elastance, longer chord length, and lower lung compliance. Importantly, we also assessed the lung function of the dams that gave birth to our experimental subjects. Even though these mice had been exposed to the same level of increased CO 2 for a similar amount of time ( ∼ 8 wk), we measured no impairments in lung function. This suggests that the early life period, when lungs are undergoing rapid growth and development, is particularly sensitive to CO 2 . DISCUSSION: To the best of our knowledge, this study, for the first time, shows that long-term exposure to environmentally relevant levels of CO 2 can impact respiratory function in the mouse.

Air Pollution and the Airways: Lessons from a Century of Human Urbanization

“…Carbon dioxide is produced by the combustion of fossil fuels or forest fires [5,18]. One recent study explored the effect of carbon dioxide alone in mice and established that it leads to a range of respiratory impairments such as higher elastance in the lung and lower lung compliance [77]. This study also showed that during early life when the lungs are still growing and under development, they are most sensitive to carbon dioxide which might lead to alveolar destruction and other lung structures [77].…”

“…One recent study explored the effect of carbon dioxide alone in mice and established that it leads to a range of respiratory impairments such as higher elastance in the lung and lower lung compliance [77]. This study also showed that during early life when the lungs are still growing and under development, they are most sensitive to carbon dioxide which might lead to alveolar destruction and other lung structures [77]. Combined with exposure to organic dust, low levels of carbon dioxide can alter immune responses leading to more airway inflammation and induction of pro-inflammatory cytokines [78,79].…”

Long‐term exposure of mice to 890 ppm atmospheric CO2 alters growth trajectories and elicits hyperactive behaviours in young adulthood

“…The environmental exposures have been detailed in (Larcombe et al 2021). In brief, adult female and male mice were randomly assigned to one of two experimental conditions; control mice (Con) were housed at 465 ± 27 ppm atmospheric CO 2 (standard housing atmospheric conditions) and the experimental group (CO 2 ) were housed at 889 ± 123 ppm atmospheric CO 2 (900 ppm was aimed at for as the predicted atmospheric conditions, exposure averaged to 889 ppm for the duration of the experiment, see Larcombe et al (2021) for more details). Both groups were allowed to acclimatise to their assigned atmospheric condition for a period of 2 weeks.…”

“…We have recently provided the first evidence, to our knowledge, that exposure of mice to 890 ppm CO 2 from pre‐pregnancy and early life through to 3 months of age elicits changes in respiratory structure and function with haematological measures indicative of borderline respiratory acidosis (Larcombe et al . 2021). The respiratory changes were observed only in female offspring and were possibly driven by exposure in early life.…”

Spatially explicit analyses of environmental and health data to determine past, emerging and future threats to child health

“…A recent study exposing pregnant mice and their newborn to concentrations of just below 900 ppm found higher tissue elastance, longer chord length and lower lung compliance in the offspring. 19 The IPCC Shared Economic Pathway 6 will approach these CO 2 concentrations and Shared Socioeconomic Pathway 8.5 will pass them by the end of this century. 20 Environmental degradation drives poorer child health in Africa.…”