Environmental determinants of allergy and asthma in early life

Abstract

Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children.

Keywords: Environment; air pollution; allergen; allergy; asthma; endotoxin; exposure; infection; microbiome; tobacco smoke.

Figure 1. Interplay of Early Life Exposures that Impact Allergic Disease Development

Allergic disease development is influenced by many different factors. This figure displays several of the identified environmental triggers that increase susceptibility to allergic disease. A) Common behaviors and determinants that influence an individual's microbiome and external microbial environment, thereby influencing susceptibility to allergic disease. B) Allergens that have been linked to development of atopy. C) Air pollution exposures that not only influence lung function but also contribute to the immune response. Collectively, this Venn diagram demonstrates the overlapping contributions of each exposure. The center of the figure shows the questions that have yet to be elucidated, including how any of the numerous combinations of these common exposures influence the onset of disease or impact severity of disease.

Figure 2. Potential Interventions Reducing Risk of Allergic Disease Development

A) Certain modifications can positively influence an individual's microbiome or select for a protective external microbial environment. B) Reducing the quantity of allergen exposure may reduce development of allergic disease. C) Although the highest pollutant exposures occur from exposure to environmental tobacco smoke, mitigating industrial and traffic related air pollution will have to come from national and local regulatory agencies throughout the world. The center of the figure highlights the questions that have yet to be elucidated. Could these interventions impact the incidence of allergic disease, and if so, which are the most pragmatic, cost-effective, and have the highest potential impact in different societies?