Asthma and Allergic Diseases

By Sashankh Parthasarathy

BIG QUESTION

Are Asthma and allergic diseases in general caused by genetic factors or environmental factors?

More specifically, is one born with asthma or is it acquired?

Smaller questions - What is asthma? And why is it so important that

we are aware of it? - Is there a cure for it?

Why I chose this topic

Although I have never had asthma, I have many allergies I was curious as to what was going on inside my body when

I was in one of my allergy periods In regards to my big question, I never understood what

caused my allergies. Was it something in my surroundings or was it something

inside of me?

Overview

The Basics of Allergies The Basics of Asthma The Sides of Asthma - Environmental Factors - Genetic Factors More Facts about Asthma My Interview Conclusion

What is an Allergy?

An allergy is an overreaction of the body’s immune system to a foreign substance, which is called an allergen.

An allergen can be ingested, injected, inhaled into the lungs, or absorbed by the skin.

Once an allergen has been introduced to the body, the body can react by producing a variety of symptoms, such as coughing/sneezing; itchy, watery eyes; a runny nose; and a scratchy throat.

In extreme cases, a person may experience a rash, hives, low blood pressure, difficulty in breathing, an asthma attack, or even death.

Allergies are characterized by the specific allergens that trigger symptoms, as well as the method by which the allergy can be introduced.

Although allergies and their symptoms can be managed, there is no known cure

What is Asthma?

Asthma is a small inflammatory disease of the small airways of the lung. The airways are tubes that carry air into and out of your lungs. People who have asthma have inflamed airways. The inflammation makes the airways swollen and very sensitive. The airways tend to react strongly to certain inhaled substances. When

the airways react, the muscles around them tighten. This narrows the airways, causing less air to flow into the lungs.

The swelling also can worsen, making the airways even narrower. Cells in the airways might make more mucus than usual.

Mucus is a sticky, thick liquid that can further narrow the airways.

Asthma is a chronic disease, which means you live it every day and once you have it, it never goes away

Figure A shows the location of the lungs and airways in the body. Figure B shows a cross-section of a normal airway. Figure C shows a cross-section of an airway during asthma symptoms.

The Environment

What sort of effect does the environment have in causing asthma and allergic diseases?

Contact with allergens, certain irritants, or exposure to viral infections as an infant or in early childhood when the immune system in developing have been linked to developing asthma.

Irritants and air pollution may also play a significant role in adult-onset asthma.

Environmental Factors

Respiratory infections such as colds, flu, sore throats, and sinus infections. These are the number one asthma trigger in children.

Physical Exercise - The kind of physical activities that can bring on asthma symptoms include not only exercise, but also laughing, crying, holding one's breath, and hyperventilating.

Work Conditions – Poor working conditions is also cited as a cause of asthma as the person may be exposed to dangerous chemicals.

To conclude, the environment plays a huge role in provoking asthma.

More About Asthma

Atopic Asthma is the most common form of the disease, and is predominantly seen in the Western world. Asthma affects 1 child in 7 in some societies and affects as many as 300 million people worldwide; this is expected to increase to 400 million by 2025. Asthma is estimated to account for 1 in every 250 deaths worldwide, resulting in 250,000 deaths each year worldwide .

A rural lifestyle is consistently associated with a low prevalence of asthma.

Asthma is more common in affluent societies. However, the tide is beginning to turn as more and more areas become modernized and industrialized. With more urban areas, there could possible more cases of asthma.

Gender-wise, asthma is more common in boys than girls in youth. However, in adults, there are more cases of asthma being in women than in men.

Allergic diseases cause widespread morbidity, leading to impaired work productivity and school performance, reduced quality of life, and

substantial medical and non-medical costs.

More About Asthma

Allergic rhinitis, clinically defined as a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation, affects 10% to 20% of the population, with an estimated over 500 million affected people worldwide.

Atopic dermatitis, a chronic inflammatory pruritic skin disease, affects 10% to 20% of children and 1% to 3% of adults worldwide.

Food allergy, defined as an adverse immune response to food proteins, affects up to 6% of young children and 3% to 4% of adults

Genetics Side

Now, we can take a look at another side of asthma – the genetics behind it.

Is asthma caused by genetic predispositions? Meaning, is asthma hereditary? Can it be passed down from generation to generation?

Genetics

Latest research states that asthma runs strongly in families, which suggests that this disease may be hereditary.

Research shows that children with one asthmatic parent are 3-6 times more likely to develop asthma and children with two asthmatic parents are 10 times to develop asthma.

One way to verify this is to use a process called positional cloning Positional cloning is a process of gene identification that begins by

finding genetic regions on chromosomes inherited by the disease. Thus far, five gene complexes have been somewhat linked to

asthma. These include ADAM33,PHF11, DPP10,GRPA, and SPINK5. While the specific function of these genes are still obscure, it is

suggested that they deal with the threat and damage from the external environment

Many of the genes identified by candidate gene studies (such as IL13) also have an effect in the cells that make up the mucus.

As we know, the buildup of mucus in the airways of the lungs leads to asthma attacks.

Genetics

PLA2G7 gene - The protein encoded by this gene is a secreted enzyme

that catalyzes the deterioration of platelet-activating factor to biologically inactive products

What the hell does that mean?

Basically, it is proved that mutations in this gene can cause a person to be more susceptible to asthma. It is an enzymatic deficiency that worsens the body’s response to inflammatory agents.

It can be associated with several disease states including inflammatory intestinal disorders, asthma and atopy.

Asthmatic individuals may show irritating respiratory symptoms.

Genetics – More Genes

IL-4Ra gene - another important candidate gene that is located in a linked region of chromosome 16q. Plays a key role in allergic inflammation

ADAM-33 – located on chromosome 20. Known to be associated with bronchial hyper-responsiveness and a decline in lung functions over time strongly point to its involvement in the structural airway components of asthma.

TNF-a is a powerful inflammatory cytokine. A cytokine is a small protein released by cells that has a specific effect on the interactions

between cells. The cytokines family include interferons, which trigger inflammation and respond to infections.

The TNF-a gene is located on chromosome 6p within the MHC complex.

On chromosome 5q there are many candidate genes for asthma and allergy such as the interleukin 4 and b2- adrenergic receptor genes.

Linkage has been replicated in all these regions and for most of them multiple candidate genes have been suggested as the reason for the linkage.

However, no DNA sequence variations that alter protein expression or function have been definitively labeled as “asthma mutations

My Interview

http://www.dnalc.org/view/15400-Chromosome-5-genes-involved-in-asthma-and-other-allergies-Matt-Ridley.html

For this project, I wanted to ask someone who actually knows a little more about the subject rather than just looking everything up on the internet. I asked my doctor back in India, who is an expert in asthma and allergic diseases. Besides from giving me an overview of what I was researching, he gave me his answer to my big question.

* Most of the information that he gave me is used throughout this presentation.

His Stance

I believe that asthma is an amalgam of both genetic factors and environmental factors. Familial concordance of a disorder can be due to shared environment as well as shared genes. Twin studies can help to determine the relative contribution of shared environment and shared genes to a phenotype. In twin studies the concordance of the phenotype in monozygotic and dizygotic twins is compared and when possible, concordance is also compared in twins who were reared together or apart. As for the environment itself, it plays a huge role in provoking asthma. As we all know, asthma is classified as an allergic disease and most allergies are caused by something outside of us. By outside, I mean that ordinary things such as peanuts or flowers or the weather can trigger allergies.

Where the research is now Another important question concerns whether the

enormous expense being committed by major pharmaceutical companies to finding asthma genes will lead to diagnostic or therapeutic innovation.

A number of major pharmaceutical companies have taken the risk, and potentially they will be able to determine the function of novel genes in linked regions, identify whole new pathways of disease production, and develop specific effective inhibitory agents that will prevent or modify disease expression

It is unclear whether their enormous investment in gene discovery will ever be repaid

The Cure

While this is sidetracking from the main question, another important questions that has been asked about asthma is whether it can cured or not.

While asthma cannot be cured, it may be managed to improve quality of life and symptoms. 

Treatment involves fast acting bronchodilators or rescue medications for the subtle symptoms. 

If symptoms are frequent or more severe, daily controller or prevention medications may be needed to decrease ongoing airway inflammation and thus minimize symptoms.

What can we conclude from all of this?

Since there are multiple genes that have some sort of effect on triggering asthma, asthma is known as a polygenic.

Conclusion

What can conclude from all this? Prior to this project, I thought asthma was mainly triggered by

environmental factors. But now after all this research and interviews that I have done, I

can safely say that asthma and allergic diseases in general are caused by both genetic factors and environmental factors. The genes present in the body have the same amount of influence in causing asthma as the environment does.

Limitations Well, I probably should’ve gotten more perspectives. I did use a

lot of articles, but I only did one interview. In the future, I will conduct more interviews and get more personal opinions.

What else would I like to learn? More about the genetics aspect of it. There are many more genes

that are involved in asthma and I’d like to learn more about it.

http://www.who.int/genomics/about/Asthma.pdf http://

www.everydayhealth.com/asthma/bronchitis-or-asthma.aspx

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http://www.aafa.org/display.cfm?id=8&cont=6 http://

www.emedicinehealth.com/asthma_faqs/page5_em.htm http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181014/ http://

www.aaaai.org/about-the-aaaai/newsroom/asthma-statistics.aspx

http://www.cdc.gov/VitalSigns/asthma/ http://

www.yale.edu/ynhti/curriculum/units/1999/6/99.06.02.x.html