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Previous Findings Regarding Widely Used Asthma Treatment Challenged

ScienceDaily (Jan. 14, 2008) — A new study published recently in The Lancet reveals that one of the most commonly used asthma medicines -- long-acting beta-agonists -- may not be associated with adverse events in people based on their genotype (gene variation), as previous studies had shown.

The study analyzed the effects of long-acting beta-agonist therapy, used in combination with inhaled corticosteroids, in asthmatics who have a specific beta-2 adrenergic receptor (ADRB2) genotype.

Investigators analyzed data from two clinical trials performed by AstraZeneca Pharmaceuticals LP. In each trial, patients were randomized to receive one of two different long-acting beta-agonists. In the case of each of the therapies, asthma symptoms and control improved, but no differences were observed based on the ADRB2 genotype.

"These results are extremely important because previous studies on short-acting beta-agonists showed evidence for an adverse genotypic effect," said Eugene R. Bleecker, M.D., Thomas H. Davis Professor of Medicine, co-director of Center for Human Genomics at Wake Forest Baptist, and lead-investigator for the study. "Smaller studies on long-acting beta-agonists have produced conflicting results."

Current guidelines recommend the use of combination therapy, with long-acting beta-agonists and inhaled corticosteroids, to control moderate to severe persistent asthma.

"With over 2,000 patients in this study receiving combination therapy, it was reassuring that no adverse safety effects could be attributed to an individual's genotype," said Bleecker.

Ten percent of the U.S. population suffers from asthma. Each year, approximately 4,000 people die with asthma as the underlying cause.

Co-investigators were Deborah A. Meyers, Ph.D., professor of pediatrics, co-director of Center for Human Genomics, and section head of Medical Genetics at Wake Forest, Dirkje Postma, M.D., professor of pulmonary medicine, University of Groningen, The Netherlands, and Helen J. Ambrose, Ph.D., Mitch Goldman, M.D., and Rachel Lawrence, B.Sc., of AstraZeneca Pharmaceuticals LP.

Conflict of interest statement: There was no pharmaceutical support of the analysis. Bleecker has received grant support to perform clinical trials from AstraZeneca, has served as a consultant AstraZeneca, and has presented Continuing Medical Education and other lectures sponsored by AstraZeneca. Meyers has received grant funding from AstraZeneca for directing a two-day postgraduate course on human genetics and pharmacogenetics in 2006 and 2007. Postma has received research funding from AstraZeneca. Ambrose, Goldman and Lawrence are employees of AstraZeneca and hold stock in the company. All the pharmaceutical industry grant support was administered through their respective University/Medical Centers for the above authors and no financial support was received by any of the authors for the studies presented in this report.


Adapted from materials provided by Wake Forest University Baptist Medical Center.
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