Some inhalers can worsen asthma, researchers find

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Some inhalers can worsen asthma, researchers find

Wednesday, March 24, 2004

By LEE BOWMAN

SCRIPPS HOWARD NEWS SERVICE

http://seattlepi.nwsource.com/health/166020_medi24.html

An ingredient found in some inhalers used to treat asthma actually acts

to worsen inflammation of the lungs over time, researchers have found.

The discovery, presented yesterday before the annual meeting of the

American Academy of Allergy, Asthma and Immunology in San Francisco,

helps explain why long-term use of inhalers has proved counterproductive

for some patients.

" We need to do further studies to understand the mechanisms, but the

findings suggest the current combination therapies involving these drugs

may not be realizing their full potential, " said Ameredes, a

research assistant professor in medicine and cell biology at the

University of Pittsburgh School of Medicine, who presented the findings.

The drug albuterol, one of a class of medicines called beta-agonists,

has been widely prescribed for asthma. It is combined with steroids to

prevent and treat asthma by relaxing and opening the muscles surrounding

air passages in the lungs.

But many asthmatics and their doctors have noticed that if the inhalers

are used too often, for too long, they can actually worsen lung function

and increase inflammation.

Beta-agonist molecules, like most molecules, have two mirror-image

forms, called isomers. Although they have the same chemical composition,

each isomer is arranged differently, much like a right hand and a left hand.

In albuterol, one of the isomers, called R-albuterol, is the active

version that binds to receptors in lung muscles to prompt them to relax.

The other isomer, called S-albuterol, has been thought to be inactive,

although researchers have noted that it takes three or four times longer

to break down in the body than the active half of the drug.

" We wanted to look at the different mechanisms of these compounds from

the perspective of the isomers, " Ameredes said, " thinking they may

explain the paradoxical airway constriction and worsening of asthma in

some patients that is severe enough to land them in the emergency

department. "

Until recently, it had not been possible to separate the two different

shapes of albuterol molecule to study the effects of the isomers.

That hurdle was overcome several years ago, but other researchers have

focused on the effects of the two compounds on airway muscles alone.

Ameredes and colleagues at Pittsburgh's Asthma, Allergy and Airway

Research Center tested airway muscle cells with the two compounds to see

whether they enhanced or nullified the anti-inflammatory effects of

steroids given at the same time.

" We found that with R-albuterol, in combination with a steroid

(dexamethasone), the muscle cells reduced production of an important

chemical signal that promotes inflammation, " Ameredes said. " We also

found that S-albuterol did not have these effects, and in fact, resulted

in increased production of that same pro-inflammatory cell signal. "

" It seems that at least some of the paradoxical responses we've observed

in asthmatics may derive from these pro-inflammatory effects, " he added.

One formulation of albuterol that contains only the active isomer is

already being used to treat asthma. It's called levalbuterol, but so far

is only being sold in a form that's administered using mechanical

nebulizers.

The drug is sold under the brand name Xopenex, marketed by Sepracor Inc.

The company recently completed human tests on the drug using the more

portable multidose inhalers, however, and is seeking approval from the

Food and Drug Administration to sell the product under prescription for

patients age 6 years and older.

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