Embargoed for Release: March 2, 2010, 11:45 AM EST
Embargoed for Release: March 2, 2010, 11:45 AM EST
A new study has found the addition of long-acting beta-agonist therapy to be the most effective of three step-up, or supplemental, treatments for children whose asthma is not well controlled on low doses of inhaled corticosteroids alone.
The study was designed to provide needed evidence for selecting step-up care for such children and was supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. Researchers also identified patient characteristics, such as race, that can help predict which step-up therapy is more likely to be the most effective for a child with persistent asthma.
The study found that almost all of its participants had a different response to the three different treatments. Although adding the long acting beta-agonist step-up was one and one-half times more likely to be the best treatment for most of the study group, many children responded best to other two treatments instead.
The results were presented March 2 at the American Academy of Asthma, Allergy and Immunology 2010 Annual Meeting in New Orleans and are published online in the New England Journal of Medicine.
"These results fill an important gap in our asthma guidelines," said NHLBI Acting Director Susan B. Shurin, M.D., a board-certified pediatrician. "At the time the guidelines were written, there were very few comparison studies conducted in children whose asthma was poorly controlled with low-dose inhaled corticosteroids. Now that we have these study data, we can more confidently make recommendations for these children."
The NHLBI's Guidelines for the Diagnosis and Management of Asthma (EPR-3) recommend three treatment options for children with mild to moderate persistent asthma - for example, those experiencing symptoms at least two days per week - whose asthma is not well controlled on low doses of inhaled corticosteroids. These treatments, which were featured in the study, are adding a long acting beta agonist to the low-dose inhaled corticosteroids; adding a leukotriene receptor antagonist to the low-dose inhaled corticosteroids; and doubling the dose of inhaled corticosteroids. These recommendations were based on data collected from adults.
The study, called Best Add on Therapy Giving Effective Responses (BADGER), compared how effectively the three different step-up treatments improved asthma control in 182 children ages 6 to 18 years. All participants had mild to moderate persistent asthma that was not controlled on low-dose inhaled corticosteroids. Participants received each of the three treatments, with each treatment period lasting 16 weeks.
Responses were measured based on three factors: number of asthma episodes requiring oral corticosteroids, number of days of well controlled asthma, and lung function as measured by the amount of air exhaled in one second.
Overall, adding a long-acting beta-agonist to inhaled corticosteroids was significantly more likely (1.5 times) to be the best step-up therapy as compared to adding a leukotriene receptor antagonist to inhaled corticosteroids or to doubling inhaled corticosteroids.
Nearly all the children responded differently to the three treatments, with 45 percent of children responding best to adding a long-acting beta-agonist, 28 percent responding best to adding leukotriene receptor antagonist, and 27 percent responding best to doubling the dose of inhaled corticosteroids.
The study also identified several patient characteristics that increased the likelihood of identifying which step-up treatment would be more effective for an individual child. For example, African-American study participants were equally likely to respond best to long-acting beta-agonist step-up or inhaled corticosteroids step-up, and least likely to respond best to leukotriene receptor antagonist step-up. For white participants, the addition of a long-acting beta-agonist was clearly the most likely step-up therapy to give the best response, with inhaled corticosteroids step-up the least favorable therapy.
In addition, a long-acting beta-agonist was more likely to be the most effective step-up therapy among children who started the study with high scores on the Asthma Control Test, a five-item health survey used to measure asthma control, and among those who did not have eczema, an allergic skin condition.
"This study underscores the fact that individuals respond differently to different therapies – childhood asthma treatment is not one-size-fits-all," said Robert F. Lemanske, Jr., M.D., of the University of Wisconsin Hospital-Madison, one of the principal investigators of the study and lead author of the paper. "It is important to monitor the child's response closely and, if necessary, adjust therapy with one of the other options within this step of care before moving to a higher step of care."
The benefit of adding a different class of medication may be because of a possible ceiling effect for low-dose inhaled corticosteroids in some children, Dr. Lemanske said.
The observed overall best performance of long-acting beta-agonist step-up should be weighed against the increased risk of severe worsening of asthma symptoms leading to hospitalization and, in rare cases, death, as noted in the U.S. Food and Drug Administration approved labeling for long-acting beta agonists. Although there were no safety differences among the treatments during this study, the researchers assert the BADGER trial was not designed or powered to evaluate long-term safety of long-acting beta-agonists in children.
"This is the kind of study that will advance strategies for personalized medicine and improve treatment for children who have asthma," said James Kiley, Ph.D, director of the NHLBI Division of Lung Diseases.
According to the Centers for Disease Control and Prevention, almost 7 million children in the United States have asthma, a leading cause of hospitalizations and school absenteeism. Common asthma symptoms include wheezing, shortness of breath, chest tightness, and coughing. While there is no cure for asthma, most children who receive effective treatment are able to control symptoms.
The study was conducted by researchers with the NHLBI's Childhood Asthma Research and Education Network (CARE) centers. The CARE Network was established in 1999 to evaluate treatments for children with asthma; study sites are Penn State College of Medicine, Hershey, Pa.; National Jewish Health, Denver; University of Wisconsin - Madison; University of California, San Diego/Kaiser Permanente Medical Center; Washington University School of Medicine, St. Louis, Mo.; and University of Arizona College of Medicine, Tucson.
CARE centers also received support for this study from the National Center for Research Resources and the National Institute of Allergy and Infectious Disease, both part of NIH. Medications were provided by GlaxoSmithKline and Merck, Inc.
To arrange an interview with an NHLBI spokesperson, please contact the NHLBI Communications Office at (301) 496-4236 or email firstname.lastname@example.org. To arrange an interview with Dr. Lemanske, please call (608) 263-6184.