Johns 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 Hopkins 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," says Alkis Togias, M.D., who led the study, which was funded by the National Institutes of Health. "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.
Attempts to link asthma with irritants or allergens have been unsuccessful so far, according to Togias
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, according to Togias.
"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," says Togias. "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 of the non-asthmatics developed breathing difficulties remarkably similar to those of asthmatics.
"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.
Other authors on the study were Gwen Skloot, M.D., a pulmonary fellow, and Solbert Permutt, M.D., director of Hopkins' pulmonology research division. The study was published in the November issue of The Journal of Clinical Investigation.
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