Dual therapy works best for controlling asthma

A combination of airway-opening drugs and inhaled inflammation-reducing steroids works better at preventing severe asthma attacks than a normal dose of steroids alone, according to a new review of recent studies.

However, higher doses of steroids seem to be just as effective as the combination therapy in preventing these attacks, a second review concludes.

The studies focus on the effects of long acting beta-2 agonist (LABA) drugs. Unlike “rescue” inhalers, which can immediately open airways during an asthma attack, LABA medications keep bronchial airways relaxed and open over a 12-hour period. The drugs include salmeterol, which is sold under the brand name Serevent and is also an ingredient in the Advair inhaler, and formoterol, sold under the brand name Foradil.

Asthma patients who used both LABA medication and an inhaled steroid were significantly less likely to have a severe asthma flare-up requiring treatment with an injected or swallowed steroid than patients taking the steroid alone, according to Muireann Ni Chroinin, M.D., of the Norfolk and Norwich University Hospital in England, and colleagues.

The reviews appear in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The rate of severe attacks dropped from 27 percent to 22 percent in patients taking the combination therapy. Ni Chroinin and colleagues calculate that 18 patients would need to be treated with LABA for one year to prevent at least one patient from having such an attack.

Combination therapy also improved overall lung function, increased the number of days where patients said they felt free of asthma symptoms and decreased the patients’ use of rescue inhalers, compared to inhaled steroids alone, the researchers found.

For patients who continue to have asthma symptoms while using an inhaled steroid medication, “the addition of long-acting beta-2 agonist is superior to remaining on similar doses of inhaled steroids alone,” Ni Chroinin says.

In a second review, Ilana Greenstone, M.D., of McGill University Health Center in Canada and colleagues concluded that a double dose of inhaled steroids worked just as well as combination therapy in reducing the rate of severe asthma attacks.

But the combination therapy “clearly leads to greater improvement in lung function and symptoms than a two- to two-and-a-half-fold higher dose of inhaled corticosteroids,” according to Greenstone. There was a 12 percent increase in symptom-free days among patients taking LABA and steroids, compared to those taking the higher steroid dose. Patients on the combination therapy also reduced their rescue inhaler use by as much as one less “puff” per day.

There were no significant differences in side effects between the combination therapy and higher steroid doses except for a three-fold increase in the rate of tremor, or uncontrolled muscle contractions, in the patients taking LABA medications, the researchers found.

Ni Croinin and colleagues reviewed 26 studies that included 8,147 patients. Greenstone and colleagues analyzed 30 studies that included 9,509 patients. Only eight of the studies in the Ni Croinin review and three studies in the Greenstone review focused on children with asthma.

“I think the lack of data for pediatrics is certainly a problem which may limit the use of LABA in that age group. There just aren’t enough studies to make evidence-based clinical decisions,” Greenstone says.

The Cochrane reviewers say their work may help physicians decide when or if to prescribe LABA medications to asthma patients already taking inhaled steroids.

“My sense is that there is a tendency to initiate combination therapy with inhaled corticosteroids and LABAs,” rather than start with steroids and add LABA drugs later on in patients with uncontrolled asthma, says Jerry Krishnan, M.D., an asthma researcher and assistant professor of medicine and epidemiology at the Johns Hopkins University School of Medicine. “This practice is likely to be driven in part by the step-down approach, where more aggressive therapy is initiated, then stepped down once control is achieved.”

Almost all the studies reviewed by both Ni Croinin and Greenstone and colleagues were sponsored by the manufacturers of either LABA medications or inhaled steroids. Francine Ducharme, M.D., an author on both reviews, has received speaking and consulting fees from AstraZeneca (producer of formoterol and the steroid budesonide), GlaxoSmithKline (producer of the steroids fluticasone and beclomethasone and salmeterol), and Novartis (producer of formoterol).