Childhood immune illnesses presage lifelong disease patterns.

What did they do?

Using distinct examples gathered from research studies, the authors make insightful connections among what is known about early life exposures, childhood disease and adult disease risk. They use these connections to develop an overarching perspective on immune-based disease. This review builds upon a series of related papers written by several of the authors.

What did they find?

The authors explain several examples of childhood diseases that are linked to environmental exposures early in life and an increased risk for adult disease. The disease patterns center around four key immune system categories: allergy, autoimmune, inflammation and infection.

For instance, childhood asthma is an entryway disease caused or exacerbated by early exposure to tobacco smoke, traffic exhaust and other pollutants. A person with asthma is at increased risk for several seemingly unrelated conditions during his or her life. These include skin allergies, ear infections, increased respiratory infections, behavioral disorders, disorders involving the sense of smell, obesity and lung cancer. But, in fact, all of these later conditions share immune dysfunction as an underlying cause.

Similarly, environmental factors like the mother's diet, diet during infancy and early childhood, or developmental exposure to tobacco smoke are known causes of metabolic syndrome. The early signs of metabolic syndrome – such as insulin resistance, high blood pressure, obesity, elevated triglyceride levels or altered cholesterol – involve an ongoing, low-grade immune response in the form of inflammation. Inflammation occurs when immune cells and an increased blood supply gather in tissue. People with metabolic syndrome are at increased risk for serious later life conditions like stroke, heart disease, type 2 diabetes or chronic kidney disease.

The authors use these kinds of examples to make the case that "significant illnesses such as asthma and type 1 diabetes are not only the end result of environmental exposures interacting with genetic background; they are the entryway into even larger environmentally associated health concerns."

What does it mean?

In this review, the authors provide evidence that several significant human diseases are related to early life exposures that negatively affect how the immune system develops and matures. This negative impact sets up a lifelong trajectory of immune dysfunction and increasing susceptibility to more serious diseases.

Because allergies, asthma and other immune-related diseases are on the rise, there is a critical need to understand the causes and outcomes of immune dysfunction. Based on their examples, the authors propose a "pattern of disease" hypothesis to explain the dramatic global rise in such chronic and debilitating diseases. This major shift in how disease is perceived may lead to better understanding, prevention and treatments.

This type of theoretical research is tremendously valuable because it can push forward new ideas for medicine and health care, ultimately identifying new research directions and strategies for disease prevention.

Historically, diseases caused by immune dysfunction are viewed as separate conditions treated by physicians with varied expertise. Patients would see a different specialist for atherosclerosis, considered a cardiovascular condition; asthma, a respiratory disease; celiac disease, a digestive malfunction; psoriasis, a skin condition; and multiple sclerosis and dementia, brain and nervous system disorders. The authors point out that an immunologist in conjunction with the other medical experts might offer a more holistic treatment for each of these conditions.

Appying their hypothesis of disease patterns, the authors conclude there are two opportunities to break the lifelong disease cycle associated with immune dysfunction.

The first is prevention. Reducing developmental exposure to environmental hazards could prevent entire patterns of disease. Especially important is to protect pregnant women and children from pollutants – a task that becomes more critical as water, air and soil are increasingly contaminated through human activities.

The second opportunity involves interrupting the disease pattern after the childhood entryway disease is diagnosed. Patients and their doctors could predictively screen for conditions for which the patient has an increased risk. The authors recommend that medical care should be directed at both controlling the underlying immune dysfunction and managing the immediate symptoms of the childhood condition.

Currently, chemicals and pharmaceutical drugs are not required to undergo testing for developmental effects on the immune system. Rather, current testing standards only check for effects that suppress – and not those that stimulate – the immune system. Inappropriate immune stimulation can lead to autoimmune diseases, dysregulated inflammation or allergic disease. Given the importance of the developing immune system to lifelong health and well-being, the authors strongly recommend that developmental immune system toxicity testing become a priority in the safety assessment of chemicals and drugs.