Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases.

The unparalleled burden of a diverse range of chronic noncommunicable diseases (NCDs) is a major global challenge in the 21st century. Chronic low-grade inflammation is a common feature of virtually all NCDs, indicating a central role of the immune system. Furthermore, as the most common and earliest-onset NCD, the epidemic of allergic diseases points to specific vulnerability of the developing immune system to modern environmental change. Indeed, many environmental risk factors implicated in the rise of other NCDs have been shown to mediate their effects through immune pathways. The innate immune system provides a clear example of this convergence, with evidence that physical activity, nutrition, pollutants, and the microbiome all influence systemic inflammation through Toll-like receptor pathways (notably Toll-like receptor 4), with downstream effects on the risk of insulin resistance, obesity, cardiovascular risk, immune diseases, and even mood and behavior. Common risk factors will likely mean common solutions, and interdisciplinary strategies to promote immune health should be an integral part of NCD prevention, with a greater focus early in the life course before disease processes are established. In this context allergic disease provides a very important early target to assess the effectiveness of environmental strategies to reduce immune dysregulation.