Asthma Symptoms Linked To Infection.

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Pittsburgh Post Gazette, PA - June 10, 2003

http://www.post-gazette.com/healthscience/20030610hasthma2.asp

Asthma symptoms linked to infection

By Anita Srikameswaran, Post-Gazette Staff Writer

About a decade ago, a young woman with severe asthma was referred to a

Denver doctor.

She already had undergone myriad tests and was taking several

medications, including powerful oral steroids, with little success. The

doctor, , of the National Jewish Medical and Research

Center, inspected the lung tissue with a special scope and took a biopsy.

When looking at a specimen under powerful magnification, noticed

what appeared to be the squiggles of a bacteria called Mycoplasma

pneumoniae. Genetic testing of other samples confirmed the presence of

the bacteria, which is a common cause of pneumonia in people younger than

40.

The patient did not have pneumonia, but decided to see what would

happen if the low-grade infection was treated.

Slowly but surely, her once-disabling asthma symptoms got better. Now

working, she no longer requires oral steroids, hospitalizations or even

visits the emergency room.

" She went from being essentially housebound to working, married with

kids, " said. " Her quality of life tremendously improved. "

The doctor began exploring the links between Mycoplasma and asthma. Last

year, in a study in the medical journal Chest, and his colleagues

found evidence of low-grade airway infection with Mycoplasma or another

bacteria called Chlamydia (not the sexually transmitted kind) in 31 out

of 55 patients with chronic, stable asthma. Six weeks of antibiotic

treatment led to significant lung function improvements for infected

patients.

" Unfortunately, we don't have an antibiotic that really kills these

organisms, " said. " We just have antibiotics that suppress them. So

it's really a long-term treatment. "

's work " remains controversial, " said Dr. Bill Calhoun, director of

the Asthma Allergy and Airway Research Center at the University of

Pittsburgh Medical Center. " [but] more and more of us now believe he's on

to something pretty important. "

He noted that scientists at the University of Wisconsin have launched a

large study to look more closely at how viruses and bacteria contribute

to asthma.

Asthma's toll

According to the U.S. Centers for Disease Control and Prevention, the

number of asthma patients doubled between 1982 and 1998. The condition

accounts for 14.5 million lost workdays among adults and 14 million lost

school days among children, and costs $14 billion annually.

Those figures have inspired researchers to work harder to uncover the

causes and workings of asthma, which could be many diseases that produce

the same symptoms.

To unravel the complicated interactions between the bacteria, allergy and

asthma, turned to mouse experiments.

In asthma, the airways get inflamed, meaning red, warm and swollen. They

are also hyperreactive, or " twitchy " as some doctors put it, so irritants

such as cold air or perfume can make them narrow, obstructing airflow.

's team noted that asthma patients with Mycoplasma infection had a

six-fold higher number of mast cells, which are associated with

allergies, in their lung tissue compared with uninfected asthma patients.

In some situations, Mycoplasma infection seems to encourage airway

inflammation, said.

If a mouse is infected with Mycoplasma bacteria, its airways become

hyperreactive and inflamed for about two weeks, and it gets over the

illness. The mouse is then sensitized to Mycoplasma allergen. The

previous infection seems to block the airway's hyperreactive response

upon subsequent exposure to the allergen.

However, explained, if a mouse becomes sensitized to the allergen

before being infected with Mycoplasma, the airways are much more reactive

than they were with either the allergen or the bacteria alone.

" Now we have a chronic model of 'asthma' in a mouse, " he said. " Timing is

everything here. "

That pathway illustrates the hygiene hypothesis, which says that

youngsters who are exposed to many germs are less likely to develop

asthma and allergy than children who grow up in very clean environments.

Because of the Mycoplasma work of and others, " I think it's

important for people with new-onset asthma to be evaluated for the

possibility of an infectious component, " said UPMC's Calhoun.

He recently treated five members of a family who developed persistent

asthma symptoms within four months of each other, soon after they all

took a plane trip. Calhoun performed immunological tests on them that

suggested Mycoplasma exposure and treated the family with antibiotics.

All of them got substantially better and only the father, who had a

history of childhood asthma, still has an occasional attack.

It's not unusual for patients with new-onset asthma to mention having a

bad cold or bronchitis shortly before their breathing difficulties began.

" Most physicians and people feel that's just a virus, " said. " But

many of these upper respiratory infections are really secondary to

Mycoplasma pneumoniae infection and not a virus. So a lot of 'viral

colds' could be Mycoplasma. "

Large epidemiologic studies would have to be done to ascertain what

proportion of asthma sufferers carry Mycoplasma or Chlamydia. also

is trying to develop a simple diagnostic test that would be less invasive

than using the special scope.

The genetic component

Not every one who gets Mycoplasma infection winds up with asthma, of

course. Those who do likely already have a genetic predisposition for the

condition.

Research into the genetics of the syndrome has been booming in the past

five years, Calhoun said. More than 20 susceptibility genes have been

identified and there are likely more. But having a gene or two doesn't

always translate into actual disease. Scientists are still working on

deciphering the interactions between various genes that could lead to

breathing problems.

According to Dr. Nash of Children's Hospital, genetic research will

eventually show that all cases of asthma are not the same.

" There are definitely going to be different diseases that follow

different courses and maybe, in time, have different therapies directed

toward them, " he predicted. " Right now if you wheeze, you have asthma and

you get pretty much a standard therapy. "

Doctors do know that " if both mom and dad have asthma, the chances are

about two-thirds to three-quarters that any child will have asthma, "

Calhoun said. Knowing that could lead parents to make choices, such as

quitting smoking, to reduce their child's risk of becoming ill.

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Controlling symptoms

_________________

Twenty million Americans had asthma in 2001, according to the National

Center for Health Statistics. There were 465,000 hospitalizations and

almost 4,500 deaths due to the disease in 2000.

More than two-thirds of asthma patients are older than 18, said Dr. Bill

Calhoun, director of the Asthma, Allergy and Airway Research Center at

the University of Pittsburgh School of Medicine. Many of them developed

symptoms as adults.

Calhoun is leading the local arm of a multicenter study of people who

have severe asthma that cannot be sufficiently controlled with standard

therapies.

A recent national survey found that two-thirds of patients who had daily

symptoms considered their asthma to be well or completely controlled.

" I find that really troubling, " Calhoun said. " If I had something that

bothered me every day, I wouldn't consider that at all well controlled. "

Guidelines from the National Institutes of Health indicate that

appropriately treated patients shouldn't have asthma episodes that

require using rescue medications more than twice a week. Getting that

symptom-free often requires inhaled steroids, which reduce airway

inflammation.

Ninety percent of asthma sufferers should be using steroid inhalers, but

only a third to a half actually do, Calhoun said. That's partly because

the severity of the symptoms can change from week to week and neither

patients nor their doctors may recognize when it's getting worse.

Dr. Nash of Children's Hospital prescribes inhaled steroids as a

first-line therapy. A nighttime cough, classically between midnight and 4

a.m., is a very specific sign of asthma, he noted.

For more information about the Severe Asthma Research Program, call

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-- Anita Srikameswaran

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Anita Srikameswaran can be reached at anitas@p... or

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