Ultrafine Particulate Matter Air Pollution Exposure Aggravates Pulmonary Responses to Influenza Infection During Pregnancy

Abstract

Air pollution, including gases, metals, and airborne particles (particulates) can pose a significant risk to public health, and collectively cause many different types of toxicity. Over recent years, toxicology research dedicated to air pollution has focused heavily on particulate matter (PM) – respirable air pollution particles of different sizes, capable of reaching the lungs and other organs. PM is divided into subclasses based upon size, including those < 10 microns in diameter (PM10); those < 2.5 microns in diameter (PM2.5); and those < 0.1 microns in diameter (PM0.1), also termed ultrafine particles (UFPs). The former two classes have regulations in place set by EPA and/or WHO, while the latter class does not. This is particularly disturbing due to the small size of UFPs. The health consequences of UFPs are still under active investigation.

UFPs and air pollution in general can have several interactions with other exposures, such as respiratory viruses including influenza. Many pollutants and respiratory viruses produce damage to tissues through a combination of inflammation, immune system effects, and oxidative stress. Co-exposures to both UFPs and viral infections may result in more adverse interactions between the two exposures, especially during susceptible periods such as pregnancy. During pregnancy, there are unique changes in the immune system that allow the fetus to grow without spontaneous rejection. This shift is also actively stimulated by PM exposure. This bias reduces the extent of influenza clearance. Immunological shifts would translate to higher viral titer in the lungs, severe inflammation of the lungs, and elevated levels of pro-inflammatory cytokines relative to non-pregnant groups.

Very few drugs are optimized for pregnant women, and there is a substantial lack of investment in new drug development and clinical trials of therapies in pregnancy. One potential way to mitigate the responses caused by UFP and influenza co-exposure in pregnant populations is through incorporation of phytochemicals into the diet. An important family of phytochemicals are the isothiocyanates. Specifically, sulforaphane (SFN) has been the major focus of isothiocyanate research, due to strong indirect antioxidant actions from induction of the NRF2-KEAP1 antioxidant transcription factor pathway. For this reason, SFN has been investigated as an indirect nutraceutical for mitigating conditions caused by oxidative stress. However, the incorporation of SFN and phytochemicals more broadly into the diet to mitigate toxic outcomes is still under debate. Therefore, we have launched a toxicological investigation utilizing a C57Bl/6N rodent model that seeks to define (a) the impact of UFPs on influenza infection severity in pregnancy; and (b) the ability of nutraceutical administration during the pregnant period to broadly detoxify UFP exposures.