Research Update: Children with Mild Asthma May Benefit from Intermittent Treatment

Children who have asthma but are experiencing few or no symptoms often stop using daily asthma medications, much to their doctors’ chagrin. However, results of a new study suggest taking medication at the onset of symptoms is better than taking nothing at all.

Standard treatment for mild asthma includes daily use of a low-dose inhaled corticosteroid to tamp down inflammation that causes symptoms such as coughing and wheezing, as well as a rescue inhaler with albuterol to treat the symptoms.

In the study, researchers at Washington University School of Medicine in St. Louis and at four other U.S. medical centers found that children with asthma who discontinued daily therapy could still get good results in controlling mild asthma by using the rescue inhaler (albuterol) followed by a low-dose inhaled corticosteroid only when they were having symptoms.

“While standard treatment was still more effective in preventing symptoms, this alternative is preferable to discontinuing the medication entirely,” says Robert C. Strunk, MD, the Donald Strominger Professor of Pediatrics at Washington University School of Medicine.

Dr. Strunk and Leonard B. Bacharier, MD, both Washington University pediatric asthma specialists at St. Louis Children’s Hospital, were co-authors on the study, published online Feb. 15 in The Lancet.

“We found that if a child is perfectly controlled on low-dose inhaled corticosteroid, an alternative to stopping the medication might be to use the inhaled steroid only when needed,” Dr. Strunk says. “But simply discontinuing inhaled corticosteroids increases markedly the risk of asthma exacerbations.”

Children would have to carry two inhalers with this method, he says, but the children in the study adapted well.

In the study, called TReating children to prevent EXacerbations of Asthma (TREXA), researchers conducted a 44-week double-blind trial on 288 children ages 6-18 who had mild asthma that was well controlled using a daily low-dose inhaled corticosteroid. The children were randomly divided into four groups. The first group used a low-dose inhaled corticosteroid (beclomethasone) daily and as a rescue inhaler in addition to albuterol when needed for symptoms. The second group also used beclomethasone daily but had a placebo rescue inhaler in addition to albuterol. The third group had a placebo daily and beclomethasone as a rescue inhaler in addition to albuterol, and the fourth group had placebo inhalers for daily and rescue use as well as albuterol.

Results of the trial showed that 28 percent of children in the group using the daily low-dose inhaled corticosteroid and a placebo rescue inhaler had exacerbations, or asthma attacks, during the trial that required oral corticosteroids to reduce inflammation. About one-third of children in the group that received daily beclomethasone and rescue beclomethasone had exacerbations, and about 35 percent of children in the group that received a daily placebo and rescue beclomethasone had exacerbations. In the children who did not use beclomethasone either daily or with symptoms, nearly half had exacerbations, despite also using albuterol.

While the childrens’ asthma was in control nearly 90 percent of the time, nearly one-fourth of children in the group that used two placebos and albuterol required two courses of oral steroids for exacerbations within a six-month period, compared with less than 9 percent of children who received beclomethasone either daily or as a rescue medication.

Parents often stop giving their child the daily, inhaled corticosteroid because symptoms are well controlled or because the drug has been shown to slow growth, Strunk says. In the TREXA study, children in the groups that received daily beclomethasone grew 1.1 centimeters less on average than those in the groups that did not, a drawback that justifies the search for alternative treatments for mild asthma, the researchers say.

“Discontinuing inhaled corticosteroids causes an increase in exacerbations in children with mild persistent asthma,” Dr. Bacharier says. “Daily inhaled corticosteroids are the most effective treatment for preventing exacerbations. Using inhaled corticosteroids as a rescue medication with albuterol may be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone and avoids daily inhaled corticosteroids administration and growth impairment.”

This is the first study in which low-dose inhaled corticosteroids were used at the same time as a rescue inhaler together with albuterol in school-age children. Between 7 percent and 12 percent of children have asthma, which is the No. 1 cause of hospitalizations in children.

Washington University School of Medicine enrolled 42 children in the trial. Other trial locations were the University of Wisconsin – Madison; National Jewish Medical and Research Center in Denver; University of Arizona in Tucson; and Kaiser Permanente in San Diego.

Martinez FD, Chinchilli VM, Morgan WJ, Boehmer SJ, Lemanske RF, Mauger DT, Strunk RC, Szefler SJ, Zeiger RS, Bacharier LB, Bade E, Covar RA, Friedman NJ, Guilbert TW, Heidarian-Raissy H, Kelly HW, Malka-Rais J, Mellon MH, Sorkness, CA, Taussig L. Preventing Exacerbations in Mild Persistent Childhood Asthma: Use of Beclomethasone Diproprionate as Rescue Therapy in a Randomized, Placebo-Controlled Trial. The Lancet. Online Feb. 15, 2011.

Funding for the study was provided by the National Heart, Lung, and Blood Institute. TEVA Pharmaceutical Industries Ltd. provided the beclomethasone dipropionate-HFA and placebo.