Why Do Intrauterine Exposure to Air Pollution and Cigarette Smoke Increase the Risk of Asthma?

Abstract

The prevalence of childhood asthma is increasing worldwide and increased in utero exposure to environmental toxicants may play a major role. As current asthma treatments are not curative, understanding the mechanisms underlying the etiology of asthma will allow better preventative strategies to be developed. This review focuses on the current understanding of how in utero exposure to environmental factors increases the risk of developing asthma in children. Epidemiological studies show that maternal smoking and particulate matter exposure during pregnancy are prominent risk factors for the development of childhood asthma. We discuss the changes in the developing fetus due to reduced oxygen and nutrient delivery affected by intrauterine environmental change. This leads to fetal underdevelopment and abnormal lung structure. Concurrently an altered immune response and aberrant epithelial and mesenchymal cellular function occur possibly due to epigenetic reprograming. The sequelae of these early life events are airway remodeling, airway hyperresponsiveness, and inflammation, the hallmark features of asthma. In summary, exposure to inhaled oxidants such as cigarette smoking or particulate matter increases the risk of childhood asthma and involves multiple mechanisms including impaired fetal lung development (structural changes), endocrine disorders, abnormal immune responses, and epigenetic modifications. These make it challenging to reduce the risk of asthma, but knowledge of the mechanisms can still help to develop personalized medicines.

Airway Remodeling in Asthma

“…Besides fibroblasts, smooth muscle cells in asthmatic airways also produce increased amounts of ECM, including collagens and fibronectin (70)(71)(72). Known environmental risk factors such as biomass fuels, cigarette smoke, and rhinovirus have been shown to stimulate the productions of ECM proteins by airway epithelial cells, ASM and fibroblasts (73)(74)(75)(76)(77). Additionally, it has been reported that the degradation products of matrix proteins, sometimes referred to as "matrikines, " regulates the remodeling process; for example, tumstatin, a type IV collagenderived matrikine, modulates ASM production of ECM proteins (71).…”

Particulate Matter, an Intrauterine Toxin Affecting Foetal Development and Beyond

“…Apart from the abovementioned well-accepted factors causing foetal underdevelopment, air pollution has also been increasingly recognised as a major intrauterine toxin [ 9 , 10 ]. The World Health Organisation (WHO) has raised the alarms regarding the gravity of poor air quality on human health in the global setting, based on the studies suggesting the detrimental health effects of direct exposure to PMs derived from fossil fuel, biomass burning and traffic [ 11 ].…”

“…For example, it has been found that living less than 200 m from a major road, meaning exposure to traffic-related air pollution, causes an increased risk of developing asthma and low lung function in children [ 20 , 24 , 25 , 26 ]. The small size gives such PMs the advantage of accessing the bloodstream in the alveoli and passing blood organ barriers, including the blood–placental barrier [ 9 ]. As such, PM 2.5 can potentially circulate in foetal blood, although the foetal level compared with the maternal level is currently unclear.…”

Beneficial Effects of Naringenin in Cigarette Smoke-Induced Damage to the Lung Based on Bioinformatic Prediction and In Vitro Analysis

“…The overall incidence of COPD is significantly higher in smokers [ 9 ]. Additionally, cigarette smoking is the major cause of lung cancer [ 10 ]; cigarette smoke exposure during pregnancy is harmful to fetal development and increases the risk of childhood asthma [ 11 ]. Obviously, cigarette smoking has already caused serious lung health problems.…”