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Why Study the Developing Immune System ?

When a child is born, she/he is immediately exposed to an new environment. The child, in an instant, goes from breathing fluid to breathing air as the tiny lungs start drawing oxygen from the air. The near instant conversion from breathing fluid to air is one of the great miracles at birth and, also one of the most important initial transitions for the child's emerging immune system. Yet, while in the womb, the child's immune system is both influenced by and inherited from the mother. As the child continues to grow in the womb, she/he is exposed to the immune response of the mother, who, in turn is responding to various exposures. Once the child is born, his/her immune system that has been developed has to now adapt to new exposures.

Moms and dads are being told to limit the child exposure to 'things that have the potential to cause harm'. Yet they are also told to make sure the enviroment is not too clean so that the child's immune system can learn and therefore develop. People are being told that it is harmful to have an enviroment that is too clean or not clean enough. Yet they are not being told what does 'too clean look like or what does it mean 'not clean enough'. With this seemingly contradictory advice, it is unclear to many families how to create the best environment for their children.

Does not clean refer to a certain level of pollution, dust, dirt, dampness and chemicals imbedded in various plastics? At what levels does the child experience health sympotms that will lead to ongoing concerns?

What do scientist actually know about the the developing immune system that can provide guidance to families, policy makes and government regulations ? It begins with knowing something about the The Development of the Origins of Health and Disease (DOHaD) Hypothesis.

What is Known About Healthy Lung Development ?

Most scientist believe that immune system and lung development occurs largely in utero and during early childhood.The Developmental Origins of Health and Disease (DOHaD) Hypothesis proposes that environmental exposures influence developmental pathways during critical periods of pre-and post-natal life, and subsequently induce permanent changes leading to disease susceptibility. The DOHaD theory suggests that predictive adaptive responses of the fetus to in utero environmental cues promote a phenotype (childs innate immune system) that is optimally suited for the postnatal environment. In other words, what mom experiences during pregnancy will be similar to what the child will be exposed to during the first 18 months of life. This is termed the in-utero-prediction.

CHILD_HypothesisIf the in utero prediction turns out to be poor, there will be a mismatch between the phenotype and the actual environment experienced. Some scientists have suggested that this may explain why the same environment can pose a risk to some infants yet be beneficial to others. The imprinting of environmental experiences on infant gene expression via epigenetic mechanisms is increasingly thought to underlie the DOHaD hypothesis. How do scientists test to see if this idea is indeed accurate? (citation)

Clearly, measuring every potential exposure would be ideal, but is just not possible. However, recognized key elements that have been shown to influence lung development include indoor and outdoor air pollutants, specific chemicals, early infections, adequate nutrition and psychosocial environments along with drugs taken during pregnancy. The individual and combined impact of these factors likely depends not only on individual genetic profiles, but also on the critical timing of exposure. This, in turn, will influence the trajectory and pattern of immunological, physiological and microbiome development, leading to manifestation of individual phenotypes from which chronic, complex diseases emerge.

Exploring these multiple and complex factors simultaneously in a quantitative and longitudinal manner is essential to understanding how allergy and asthma develop.Studies of the origins of allergy and asthma must be rooted in a broad-based, longitudinal design which recognizes both pre- and post-natal environmental exposures as well as genotypes. This is why the CHILD Study was undertaken and we are hopeful to contribute to knowing more and sharing this knowledge with moms and dads.


Why Undertake a Healthy Child Development Study that Focuses on Asthma and Allergy?

Allergy and asthma are the most prevalent conditions of childhood and early adulthood, representing the 'canary in the mine' for future chronic diseases.

The allergic state ('atopy') results from interactions of susceptibility genes (nature) with environmental stimuli (nurture) in many individuals worldwide, leading to hayfever, asthma, eczema, food and occupational allergic diseases. Allergic disease, (along with obesity, which shares many common biological causes), is one of the most common childhood health problems, placing a tremendous psychosocial and economic burden on Canada and throughout developed and, in recent years, developing nations. This is reflected in decreased quality of life, as well as substantial direct healthcare and indirect costs. Moreover, many private and public health plans in Canada do not adequately meet the needs of patients for whom medical management is important.

Economic disincentives to adherence to best medical advice and poorly designed drug plans contribute to an increased burden of disease and less than optimal health outcomes. With our healthcare system facing unavoidable economic constraints, AllerGen is committed to contributing to health policies that promote adherence to management guidelines for allergic disease and asthma and lead to better health outcomes and overall cost savings. Ongoing research is required to assess and guide this commitment. Atopy can unpredictably become worse and lead to chronic allergic/inflammatory diseases, which have increased markedly in prevalence in the Western world and in rapidly-industrializing countries over recent decades. Several large epidemiologic studies–e.g., the International Study of Asthma and Allergies in Childhood (ISAAC), the European Community Respiratory Health Survey (ECRHS), and AllerGen's own research–continue to demonstrate that in Canada and globally the prevalence rates in children remain very high for hayfever (30-40%), asthma (15-20%) and food allergy (7.5-8%). There is evidence that certain chronic diseases in adults may arise, in part, as downstream health consequences of 'immune deviation' and inflammation, and manifest first as allergy and asthma in childhood.

In a 2007 report on children's health, "Reaching for the Top", commissioned by the federal Minister of Health, and prepared by Dr. Kellie Leitch, the Minister's Advisor on Healthy Children and Youth, listed asthma and allergies among the top five priorities to be addressed and supported by increased federal and provincial funding. A January 2011 follow-up conference on this topic, The Sandbox Project, confirmed Dr. Leitch's original recommendation of support for "… a Longitudinal Cohort Study to provide data on the health of Canadian children and youth to help understand environmental factors impacting children's health."

The CHILD birth cohort study is generating important new public health and policy information to examine the origins of allergy, asthma and associated environmental, nutritional and genetic triggers, from pregnancy and throughout childhood. The goal of the CHILD Study is to reveal the causes of allergic diseases through research into the health consequences of exposure to environmental triggers of allergy in air, food and water in the home environment and even as early as in pregnancy. CHILD will deliver valuable data on pregnant mothers' exposures to allergenic food components, pollens, infections, pollutants, toxicants and all types of psychosocial stress.

CHILD will also set the stage for decades of future analysis and discovery of new diagnostic tests, therapies, public health measures, food and housing standards and regulations, and other innovations to better manage, prevent and even reverse or cure these chronic conditions that impose tremendous health and economic burdens and other impacts on society, especially in an era of rising health costs.

Allergy and asthma cost the Canadian economy billions of dollars in healthcare costs and lost productivity. There is an increasing economic and social burden of allergic diseases, especially on families and their children and in the workforce.

According to the Phase III ISAAC Study (2003), 47% of Canadian children have suffered from allergic rhinitis; 39% have experienced wheezing; 22.4% have been diagnosed with asthma; and 19% have experienced atopic eczema.

According to Health Canada, non-food allergies are now the most common chronic condition in Canadians 12 years of age and older. The economic impact of these diseases in Canada is in excess of $15 billion annually, when one includes the cost of ambulatory care, in-patient stays, emergency department (ED) visits, physician and facility payments, prescribed medications and productivity losses at school, work and at home. This annual cost is comparable to the economic impact of arthritis and other chronic conditions. Ontario data show that 14% of all asthma-related ED visits occur in children between birth and four years of age, and that 21% of asthma cases were children and adolescents up to 19 years of age. Globally, asthma is more prevalent among the developed countries and in major city centres. Among the countries with lower prevalence rates, such as India and China, which represent 37% of the global population, recent research suggests that as these countries industrialize and modernize, allergy, asthma and related immune disease rates are rising rapidly, mirroring the experience of more developed countries. A recent analysis by Teresa To, The Hospital for Sick Children in Toronto, reveals that for Ontarians, the lifetime risk of developing chronic asthma is one in three – the same as the risk of developing cancer and diabetes. However, unlike cancer and diabetes, the substantial lifetime risk of asthma begins early in life and persists throughout the life span, triggering heightened disease burden, productivity loss and other economic costs.

The CHILD Study, linking with AllerGen, provides a significant opportunity to work in global networks to accelerate the translation of research into practice, and knowledge to action, to improve allergic disease and asthma awareness, education, management and control – all of which will have lasting benefits to individuals and society through minimization of downstream, long-term impacts associated with this prevalent childhood chronic disease.


Reading List - Developmental Origins of Health and Disease Hypothesis

  • Wadhwa PD, Buss C, Entringer S, Swanson JM. Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms. Semin Reprod Med 2009; 27(5):358-368.

  • Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr 2007; 27:363-388.

  • Martino D, Prescott S. Epigenetics and prenatal influences on asthma and allergic airways disease. Chest 2011; 139(3):640-647.

  • Gluckman PD, Hanson MA, Beedle AS. Early life events and their consequences for later disease: a life history and evolutionary perspective. Am J Hum Biol 2007; 19(1):1-19.

  • Hanson M, Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD. Developmental plasticity and developmental origins of non-communicable disease: Theoretical considerations and epigenetic mechanisms. Prog Biophys Mol Biol 2011; 106(1):272-280.

  • Lin KW, Li J, Finn PW. Emerging pathways in asthma: Innate and adaptive interactions. Biochim Biophys Acta 2011.

  • Minnicozzi M, Sawyer RT, Fenton MJ. Innate immunity in allergic disease. Immunol Rev 2011; 242(1):106-127.