Asthma drug increases risk for patients : study

Washington, July 17: The use of bronchodilators, a popular asthma medication, increases the risk of hospitalisation and death of the users, a study indicates.

Previous evidence had indicated that the drugs might cause adverse reactions in a small number of patients, but the latest study on the effects of the drug, after an analysis of 19 previous studies on the same, suggests the danger might exist for a wider range of patients.

According to the study published in the 'Annals of Internal Medicine,'Bronchodilators (beta-agonists) work by relaxing the muscle bands that tighten around airways, rapidly opening the airways and letting more air into the lungs. Long-Acting Bronchodilators (LABAs), such as Advair, Foradil, and Serevent, work slowly over a 12-hour period.

The active ingredient in Serevent is salmeterol, while Advair is a combination of salmeterol and fluticasone, an inhaled corticosteroid. The active ingredient in Foradil is Formoterol.

This latest study is not the first to raise concerns over the drugs. Previous trials showed an increase in asthma-related deaths and life-threatening experiences in patients on the medication. A research on patients using salmeterol studied 26,000 participants for six months and found a four-fold increase in the number of asthma-related deaths.

After a review of the drugs in July 2005, a Food Drug Administration (FDA), (the regulatory authority of drugs in the United States) advisory committee recommended new black box warning labels on Advair, Serevent, and Foradil.

In November, the manufacturers of the drug (GlaxoSmithKline for Advair and Serevent, and Novartis for Foradil) were asked to adhere to the warning labels.

In March, FDA and GlaxoSmithKline agreed to new labeling changes to Advair and Serevent, warning that the drugs should only be used after other medications have been tried and failed. FDA is still in negotiations with Novartis over the labeling of Foradil. The new meta-analysis published now summarised the data from 19 previous trials involving a total of 33,826 participants with asthma. The study found that the risks for severe exacerbations and asthma-related deaths were increased between two- and four-fold.

The study says ''We must also look at the absolute risk increase to put this into clinical perspective. We found that the absolute increase in asthma-related deaths was estimated to be .06 per cent to .07 per cent over six months, indicating that long-acting beta-agonists cause an excess of approximately one death per 1,000 patient-years of use.'' According to the study salmeterol ''may be responsible for about 4,000 to 5,000 asthma-related deaths that occur in the US each year.'' However, the researchers did admit to some limitations adherent in their analysis.

''Standard meta-analytic results for ORs (odds ratio) and risk differences can be uncertain when the numbers of events per study are small, as is the case with asthma-related deaths,'' they stated.

''The accurate assessment of asthma-related deaths in this analysis was further hindered by the fact that many trials did not provide this information.'' In an accompanying editorial in that issue of the Annals of Internal Medicine, Dr Jeffrey Glassroth said that, while LABAs are obviously potent, complex drugs that must be used with care, there are factors that have yet to be fully examined.

''The study does not completely address the possible roles of disease severity, co-treatments, and adherence in causing serious adverse outcomes, presumably because too few studies reported this information,'' the editorial states.

Meanwhile, several studies are being conducted on the beta-agonists at GlaxoSmithKline, including research into genetic risk factors and how genes play a part in patients' response to the medication.

UNI