UTMB researchers receive $3M asthma grant

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UTMB researchers receive $3M asthma grant

By Ted Streuli

The Daily News

Published August 15, 2001

GALVESTON - There is nothing more precious than air. Though we can survive

for days without food or water, we can live mere minutes without air. And

when our supply of that most necessary gas is threatened, we panic.

It's a fear asthma patients live with every day.

When a patient suffers an attack, the tube that carries air to the lungs

constricts, making it hard to breathe. Symptoms include tightness in the

chest, wheezing and shortness of breath. Severe attacks result in trips to

the emergency room, causing missed days at work or school and significant

medical bills.

Scientists at the University of Texas Medical Branch in Galveston, about 65

of them in all, are trying to put an end to the disease.

UTMB recently received a $3 million grant for asthma research from the

National Institute of Allergy and Infectious Diseases. That made UTMB one of

just Asthma and Allergic Diseases Research Centers in the United States.

UTMB beat out such noteworthy medical institutions as s Hopkins to get

the highly competitive grant.

Growing problem

Asthma is a disease on the rise.

Although physicians and scientists know more than ever about the disease,

the number of asthma patients continues to increase.

Health officials estimate 150 million people suffer from asthma worldwide

and the disease is responsible for 100,000 deaths each year.

The incidence of self-reported asthma in the United States rose 75 percent

from 1980 to 1994. From 1994 to 1998, the number of cases went up another 26

percent - from 13.7 million to 17.3 million cases.

Although Texas ranks just below the national average for prevalence of the

disease - it afflicts about 6 percent of the population here as opposed to

6.4 percent nationally - the state follows only California and New York in

number of cases

About one-third of those patients are children.

Asthma acts like an allergy and could be called an allergy of the lungs.

But not all asthma attacks can be traced to an allergic trigger.

Exercise, for example, can induce an asthmatic reaction. So while there is

overlap between allergies and asthma, there's a portion of the disease that'

s clearly not an allergic reaction.

There is hope on the horizon, however.

Eleven UTMB researchers - or " investigators " as they call themselves - are

studying asthma, its triggers and ways to stop it.

Each project tackles the problem from a different perspective, but the

investigators routinely meet to share information.

The asthma paradox

Dr. Rafeul Alam, the director of the Allergy and Immunology division at UTMB

's Department of Internal Medicine and one of the asthma investigators,

noted the irony of the numbers of sufferers increasing at a time when

knowledge about the disease also is increasing.

" Asthma has come into the national focus in the last few years, in part

because of this paradox, " he said. " Medicine is making great progress, but

in asthma we're going backwards. The number of people becoming sick is

increasing - that's the asthma paradox. "

Alam said researchers think the increase in asthma might be a result of

industrialization and what he called " westernization. "

The theory is that technology and modern, tightly sealed indoor environments

are increasing exposure to more of the triggers that set off an asthma

attack.

Human beings haven't changed dramatically, " said Alam, " so the logical place

to look for a cause is the environment. This dilemma has to be solved in two

ways - the environment and the human being and the interaction between the

two. "

One study showed that while the Berlin Wall separated Germany there was a

higher rate of allergies and asthma in West Germany, even though it had

cleaner air. When the wall came down, the incidence rate evened out.

" That raised an awareness, " said Alam. " Something is going wrong. We have to

look at it or it may go out of control. "

Looking for answers

Alam said the UTMB investigators are trying to understand the disease and

why the body reacts as it does.

" We focus on real basic research at the cellular and molecular level, " he

said. " If we don't have an understanding of the basics, we don't have an

understanding of the disease. "

Dr. Allan Brasier, UTMB's Leon Bromberg professor of medicine, has studied

asthma since 1985.

" The major advance in understanding asthma is that this airway reactivity is

the result of inflammation, " said Brasier. " The recognition of that

inflammation has revised how asthmatics are treated. What we don't know is

what causes the inflammation in the first place. "

What scientists know is that when a trigger appears in the lung, the cells

there, called epithelial cells, produce a protein that advises the body's

immune system of a potential problem.

In a healthy person, the immune system decides whether the problem poses a

great enough risk to warrant a full-scale attack and either sends cells -

called T lymphocyte, or T cells for short - to deal with the intruder or

chooses to ignore the problem.

Even if the immune system decides to launch an attack, the cells it sends to

the lung normally go in, deal with the intruder and leave. But something in

that process goes haywire in asthmatics.

" The T cells say, 'I know what you are, but you're benign and not worth the

time,' " said Alam. " In asthma patients, the T cells make the wrong decision

and attack, sending in soldiers. "

Those soldiers, white blood cells called eosinophils, work with other cells

to attack the intruder, then leave - unless the person has asthma. In an

asthmatic, those cells stay, changing the makeup of the lung.

" The big question is, What causes some people to have those cells? " said

Brasier. " That's the $64 million question. "

Eosinophils - the soldiers - store toxic ammunition that's released when

they're called to the airway to attack the intruder.

That causes the airway's smooth muscle to constrict, restricting the flow of

air. The cells can also destroy the airway's lining - creating easier access

for allergens - or cause the airway to swell.

Alam's work

The 11 investigators and their staffs of two to 10 students and scientists

are each searching for a way to interrupt that process.

Alam's research led to one patented inhibitor and he has an application for

a second patent being reviewed. But it takes five to 10 years to go from the

basic research being conducted in Galveston to the market. Drugs must got

through clinical trials.

" The goal is to narrow it down until we come up with an inhibitor that is

most selective in the cells it affects, " said Alam. " We can never predict

which one will become a clinically useful drug.

" Our main goal is to understand the processes, how they work and how they go

out of control. If we have that understanding we can come up with an

intelligent inhibitor that will be much more powerful than any of the ones

we have now. "

Alam's approach is to find a way to block the communication between the T

cells and the soldiers, eosinophils.

" In my laboratory we try to understand how these proteins activate

eosinophils to come into the airways and release the toxic molecules, " said

Alam.

Alam said that continued research might lead to an inhibitor that affects

only the eosinophils.

Brasier's work

Brasier is looking for a way to keep the soldiers from entering the airway

while allowing other, helpful cells to pass through.

His research is focused on the eosinophils' attraction to a virus known as

RSV or respiratory syncytial virus.

All humans are infected with RSV by the time they're 3 years old and get it

repetitively throughout their lives.

In a non-asthmatic, the symptoms amount to a bad cold, and the patient

recovers quickly. But when a child with asthma is infected with RSV the

first time, the results can be harrowing. A severe infection can leave the

patient with chronic wheezing for five to 10 years.

Asthma can be brought on by environmental, genetic and viral influences, and

Brasier's work is limited to the virus.

Thanks to technology that's become available within the last two years

called a DNA microarray, Brasier is able to examine 10,000 genes in one

experiment.

" We can get a lot of information on how the cell sees and responds to the

virus, " said Brasier.

The research led to Brasier and another UTMB investigator, o Garofalo,

being able to identify the hormones that attract eosinophils.

" That gives us a lot of information about how the alarm signals are sent out

and which ones we might want to block, " Brasier said.

Even though asthma is on the rise, scientists believe they're on the right

path to find better treatments, a cure and perhaps a vaccination.

" My prediction is that at some point all children will be vaccinated against

allergies and asthma, " said Alam. " But initially it will be looked at within

the high-risk population. If it works with them, it would be given to

everyone. "