Reviews and feature article
Early-life environmental determinants of allergic diseases and the wider pandemic of inflammatory noncommunicable diseases

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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.

Section snippets

A global health challenge of pandemic proportions

Dramatic environmental and lifestyle changes of the modern age pose a significant threat to human health. An unparalleled increase in a diverse range of chronic noncommunicable diseases (NCDs) is one of the major global challenges of the 21st century. This growing burden of NCDs currently poses the greatest threat to health in both developed and developing regions and is a major barrier to human development. The dominant focus of the NCDs agenda is usually on “the big four”: cardiovascular

Inflammation as a common feature of many NCDs: A central role of the immune system

Chronic low-grade inflammation is a common feature of virtually all NCDs, highlighting the central multisystem interactions of the immune system.2 The specific vulnerability of the immune system to recent environmental changes is also reflected in the dramatic increase in virtually all inflammatory disorders and, in particular, immune diseases, such as allergy and autoimmunity. Furthermore, clinical expression of allergy within the first months of life and detectable immune dysregulation at

Early life: A critical time of risk and opportunity

Prevention is the ultimate approach to reducing the burden of NCDs, and the greatest potential for this lies in early life. There is already substantive evidence that initiatives to promote a healthy start to life can reduce the risk of both early and later NCDs, with wide social and economic benefits.6, 7 The early environment in both pregnancy and early childhood can determine physiologic, structural, immune, metabolic, and behavioral development and modify response patterns that influence

Common risk factors mean common solutions: The need for interdisciplinary collaboration

Although genetic factors can determine individual susceptibility and patterns of disease, only environmental change can account for the rapid increase in NCDs. This also suggests common risk factors and the need for common solutions. Moving forward, there is a clear imperative for coordinated interdisciplinary strategies, particularly those focused on early life. There are a number of good examples of immunomodulatory interventions explored for allergy prevention that might have additional

Epigenetics, genetics, and evolutionary perspectives

The TH2 responses that characterize allergic disease are not inherently pathological and only cause disease when excessive or misdirected. Provoking new thoughts and challenging long-held concepts that TH2 responses have primarily evolved to defend against helminthes, Palm et al73 have recently proposed that the very rapid, acute IgE-mediated responses are equally, if not more likely, to have evolved to protect against a broader diverse range of environmental irritants, toxins, venoms,

Thinking beyond health to find solutions

Our current global health crisis is a major threat to social and economic development worldwide, and it is increasingly important that we (working in health) collaborate with other sectors in finding solutions to the many global challenges facing humanity and our planet. Human health is inexorably linked with the health of our natural environment. Threats, including global warming, decreasing biodiversity, and modern pollutants, have repercussions for food, water, and energy security. Equally,

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    Supported by a Practitioner Fellowship from the National Health and Medical Research Council (NHMRC) of Australia.

    Disclosure of potential conflict of interest: S. L. Prescott has received grants from the National Health and Medical Research Council and is a board member for Nestlé, Danone, and ALK-Abelló.

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