Immune effects of airborne pollutants on pregnancy, offspring and respiratory diseases in preclinical models: Therapeutic potential of non‐digestible oligosaccharides

Abstract

Air pollution refers to the release of harmful pollutants into the atmosphere, posing significant risks to human health. Alarmingly, nine out of ten individuals reside in regions that exceed WHO's recommended air pollutant safety thresholds with the most profound impact felt in low- and middle-income countries. The classifications of air pollution include ambient air pollution (AAP) and household air pollution (HAP), both of which exact a heavy toll on global well-being. In the years 2019 and 2020, AAP and HAP were accountable for 4.2 and 3.8 million deaths across the globe, respectively. HAP encompasses the chemical, biological, and physical contamination of indoor air and environmental cigarette smoke (CS) is a significant contributor to HAP. The rise in exposure to both HAP and AAP has emerged as a major environmental health crisis with compelling evidence linking these pollutants to a higher prevalence of pollution-related diseases, including conditions like allergic asthma. Remarkably, the Environmental Protection Agency has revealed that indoor air quality within homes and offices can be up to five times more polluted than outdoor air, and sometimes even a staggering 100 times more contaminated. The escalating pervasiveness of air pollution and its far-reaching health ramifications underscore the significance of this thesis. The core objective of this research is to explore the detrimental consequences of prenatal and postnatal exposure to cigarette smoke (HAP), using both in vitro and in vivo models. This thesis unfolds with evidence showcasing that maternal exposure to cigarette smoke during pregnancy and lactation leads to airway hyperresponsiveness and an elevation in inflammatory cell accumulation in the lungs of pregnant individuals compared to their non-pregnant counterparts. Notably, maternal cigarette smoke exposure, both pre- and postnatally, triggers noteworthy modifications in immune responses within the offspring. An intriguing finding within this investigation is the potential role of epidermal growth factor (EGF) as a link between maternal cigarette smoke exposure and infant immune hypersensitivity. We further showed that maternal cigarette smoke exposure skews immune responses in offspring towards an imbalanced state, culminating in heightened allergic immune responses. This is evidenced by increased infiltration of eosinophils and neutrophils in the offspring's lungs, coupled with altered lung function parameters. The study also points out that prenatal and postnatal cigarette smoke exposure leads to elevated Th2 cell frequency and augmented Th2 cytokine levels in bronchoalveolar lavage fluid, thereby contributing to exacerbated allergic manifestations in the lung. By using in vitro models, we further demonstrated that chronic exposure to air pollution could results in elevated immune response against the allergen stimulation. Notably, certain non-digestible oligosaccharides (NDOs) possess prebiotic and immune-modulating properties. The research identifies that a specific NDO mixture, used as a nutritional supplement, could mitigate lung emphysema induced by lipopolysaccharide (LPS) exposure. Consequently, NDOs emerge as promising candidates for infant formula supplementation, capable of bolstering the immune system and safeguarding against the adverse impacts of early-life exposure to air pollution on both respiratory and immune systems.