Johns Hopkins Gazette: November 6, 1995

The War on Asthma:
Uncommon Theory Gets Unlikely Boost

Michael Purdy
JHMI Office of Public Affairs

     Hopkins scientists who favor a radical theory about the
causes of asthma have dramatic new experimental support: they've
made non-asthmatic persons wheeze.

     The researchers think constricted muscles in the asthmatic
lung fail to relax in response to deep breaths, while muscles in
a normal lung do. To test the theory, they asked non-asthmatic
volunteers to avoid taking deep breaths during a standard test
for asthma.

     "The non-asthmatics suddenly began to have breathing
difficulties remarkably similar to those of asthmatics," said
Alkis Togias, an assistant professor in the Department of
Medicine, who led the study. The findings will be published in
the November issue of The Journal of Clinical Investigation.
"This strongly supports the unconventional asthma theory that we
favor," he said, which could help open up new possibilities for
treatment and monitoring of asthma.

     In an asthma attack, smooth muscles that line the air
passages of the lungs become constricted, impairing breathing. 
For years, scientists have speculated that this resulted from an
unusual reaction in the muscles to inhaled irritants or
allergens, such as pollutants or pollen. But attempts to
demonstrate this link have been unsuccessful so far, Togias said.

     "We believe muscles around the breathing passages of both
asthmatics and non-asthmatics react the same way to inhaled
irritants--they contract, closing up the air tubes," Togias said.
"We suspect that non-asthmatics overcome this reaction by using
deep breaths to relax the muscles and open up the air passages,
and that asthmatics lack this ability." 

     To test the theory, Hopkins physicians used an inhalant drug
that, in small doses, provokes breathing problems in asthmatics.
Small doses of this drug normally produce little to no response
in non-asthmatics.  

     To disable what they think is the lung's primary recovery
mechanism, researchers asked non-asthmatics to avoid deep breaths
during a series of exposures to the drug. All the non-asthmatics
developed breathing difficulties remarkably similar to those of

     "We've shown that the smooth muscle of the non-asthmatic
responds exactly the same to the inhalant as the smooth muscle of
asthmatics," Togias notes.  "This is just the reaction we would
expect if asthma is caused by an impairment of muscle relaxation
triggered by deep breaths."

     Experiments in animals have shown that deep breaths relax
smooth muscle.

     Surprisingly, though, the breathing difficulties continued
even after non-asthmatics were allowed to inhale deeply again. 
Togias speculates that multiple inhalations without a deep breath
may have allowed constriction to build up to a point where the
natural relaxation mechanisms triggered by deep breaths were no
longer as effective even for non-asthmatics.

     Further studies of these relaxation mechanisms could help
solve the mystery and lead to better treatments for asthma.

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