The Allergy-Asthma Connection

February 2016

Clinical trial patient taking test to evaluate lung function. Many patients with food allergy also have asthma and other atopic diseases.

During the last few decades, a dramatic rise in allergies and asthma on a global level has created an urgent need within the medical community to halt this increase. In response, the Sean N. Parker Center for Allergy and Asthma Research at Stanford University has teamed with Stanford’s Division of Pulmonary and Critical Care Medicine, expanding its mission to find the causes and cures for both allergies and asthma.

Why are allergies and asthma increasing in the population? Can we predict who will develop allergies or asthma and how severe their symptoms will be? How can these diseases be prevented? Who will experience progression of the diseases? Who will outgrow them? Can we cure patients with asthma or allergies? These are just some of the vital questions that physicians and scientists at the Center and around the world are tirelessly pursuing. What we have found is that allergy and asthma are interconnected, employing some of the same underlying mechanisms.

There appears to be a natural progression of onset of allergic diseases, termed the Allergic March

The Allergic March – from Allergy to Asthma

Common allergic diseases include atopic dermatitis (eczema), allergic rhinitis (hay fever), food allergies, and allergic asthma. Interestingly, there appears to be a natural progression of these diseases, suggesting the presence of common mechanisms of action.

Often, the first manifestation of allergic disease is eczema, occurring during infancy or early childhood. It is found in 10-20% of all children. Food allergies also develop early in life. These early allergic diseases are often followed by asthma and hay fever. In fact, studies have shown that two-thirds of patients with eczema develop hay fever and one-third develop asthma. The natural progression of these diseases from eczema to food allergies to asthma to hay fever is termed the Allergic March, alternatively known as the Atopic March. Not all children follow this trend and there are variations. Some children outgrow their allergies and asthma and some develop asthma and allergies for the first time in adulthood.  

Dysfunction in the Immune System Gives Rise to Disease

Both allergies and asthma are caused by a dysfunction of the immune system—an amazing system that works hard to keep us healthy and protect us from the dangers present in the environment or within ourselves. Our immune system is a sophisticated defense system with a wide range of armaments in its repertoire. It can distinguish harmless substances from harmful ones and one’s own healthy cells from foreign or damaged ones. Moreover, it protects us from bacteria, viruses, parasites, and other foreign substances. Immune cells, small chemical molecules, and large biomolecules within our body stay vigilant and are poised to attack invaders. Many of these cells and molecules circulate within the body and are recruited to seek and destroy foreign substances in diverse organs such as the skin, gut, nose, or lungs.

However, this system is not infallible and dysfunctions within the system can give rise to diseases like allergies and asthma, which may be triggered by the overreaction of immune cells to harmless substances in the environment, such as pollen, pet dander, insect allergens, environmental pollutants, or even some common foods. On exposure to these allergens, the body’s defense system is activated. In asthma and many allergic diseases, the immune system starts to produce excessive amounts of IgE—a type of antibody that is commonly detected by skin prick tests or blood tests.

Allergic diseases employing IgE-mediated response mechanisms to common allergens are called “atopic diseases” – coined after the Greek word atopy meaning “different.” However, not all allergic diseases are IgE-mediated. The mechanism of non-IgE mediated allergic diseases, such as eosinophilic esophagitis and food protein-induced enterocolitis syndrome, however, are poorly understood and are being actively investigated.

The Rise of Atopic Diseases

In the last few decades alone, marked increases in atopic diseases have been observed. Scientists have come up with a number of hypotheses involving dietary, genetic, epigenetic, environmental, and lifestyle factors–in-utero and during childhood–that may be responsible for the increase.

Individuals with a certain mutation in the filaggrin gene have been found to be at increased risk for eczema. This gene has an important function in the epidermis or upper layer of the skin. Scientists at the Sean N. Parker Center for Allergy and Asthma Research have also found that increased exposure to environmental pollutants leads to the formation of chemical tags (epigenetic modifications) on the DNA of a key gene, Foxp3, involved in asthma. Epigenetic modifications, which act as on and off switches, regulate the expression of genes and may be one factor involved in the rapid rise in asthma and allergic disease.

Although atopic diseases have a genetic component and are more prevalent in individuals with a family history of allergic disease, the observed rapid increases in allergic diseases cannot be explained by changes in genes alone.  Atopic diseases are complex and likely caused by a number of factors rather than a single cause. For example, dietary changes in the past decades are thought to have changed the type of microbes in the gut, making us more susceptible to allergies.

Another theory that attempts to explain the increase in atopic disease is the hygiene hypothesis. This hypothesis suggests that as we have adopted modern lifestyles limiting our exposure to natural substances in the environment, our excessive cleanliness prevents our bodies from adapting to the environment when we are still in the womb, infants, or young children. Frequent exposure to the outdoors and regular contact with animal and pets — as was common in earlier generations — is thought to have protected us from allergies and asthma by increasing our exposure to different microbes and substances in the environment and desensitizing us to common environmental allergens.

Leading the Way

The Center continues to spearhead innovative research in allergies and asthma. In addition to integrating the Center within the Division of Pulmonary and Critical Care Medicine, we are continuing to collaborate with key partners with the goal of advancing research, training, education, community outreach, and patient care. By comprehensive, robust, and collaborative science, we plan to find the causes and cures for allergies and asthma. Read more about the Center, its key accomplishments, its vision and mission in an interview with Dr. Kari Nadeau, the Director of the Center.

By Vanitha Sampath

Vanitha Sampath received her PhD in Nutrition from the University of California at Davis. At the Sean N. Parker Center for Allergy and Asthma Research, as a medical writer and content manager, she enjoys being in the midst of groundbreaking research in asthma and allergy and is committed to communicating the scientific advances of the Center and spreading awareness of its mission and vision. 

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