An inactive agent used in beta-agonist inhalers to treat asthma can reverse the beneficial anti-inflammatory effects of inhaled steroids, according to a recent study.
The findings may explain the paradoxical airway constriction and worsening of asthma in patients with continued use of beta-agonists such as albuterol.
Researchers at the University of Pittsburgh School of Medicine tested human airway smooth muscle cells to determine the effect of different isomers of albuterol—the active (R)-albuterol and the inactive (S)-albuterol—in combination with a simultaneously applied inhaled steroid. Recent advances allowed the separation, testing, and clinical administration of these compounds.
The researchers, led by Bill Ameredes, PhD, research assistant professor of medicine and assistant professor of cell biology and physiology, in the division of pulmonary, allergy, and critical care medicine, found that the active isomer amplified the anti-inflammatory effects of the steroid dexamethasone by reducing human airway smooth muscle cell production of a pro-inflammatory chemical signal.
The team found less favorable results for the inactive isomer. (S)-albuterol resulted in increased production of the same pro-inflammatory cell signal, Ameredes says.
“Thus, the reductions normally produced by the steroid were nullified by the inactive isomer of the beta-agonist. These results indicate that (S)-albuterol may diminish the beneficial anti-inflammatory effects of steroids by a mechanism that is not currently understood, and suggest that some of the paradoxical responses observed in asthmatics may derive from the pro-inflammatory effects of the (S)-isomer,” Ameredes says. He adds that the (S)-isomer of albuterol stays in the body three to four times longer than the beneficial (R)-isomer.
While Ameredes cautions that further research is needed, he says that some consideration should be given “to the possibility that current combination therapies involving racemic beta-agonists may not be realizing their full potential.
“It is possible that future focus on the therapeutic and nontherapeutic effects of isomers may reveal new combinatorial applications that can be beneficial to many sufferers of obstructive inflammatory lung diseases like asthma,” he says.
The study was presented March 23 at the annual meeting of the American Academy of Allergy, Asthma, and Immunology in San Francisco.