Embargoed for Release: May 10, 2006, 5:00 PM EDT
Embargoed for Release: May 10, 2006, 5:00 PM EDT
Daily treatment with inhaled corticosteroids can reduce breathing problems in pre-school-aged children at high risk for asthma but they do not prevent the development of persistent asthma in these children, according to new results from the Childhood Asthma Research and Education (CARE) Network supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.
Studies in older children and adults show that the most effective long-term control medicine for persistent asthma (symptoms more than two days a week or more than twice a month at night) is inhaled corticosteroids, which reduce airway swelling and help prevent asthma symptoms (e.g., asthma attacks). The Prevention of Early Asthma in Kids (PEAK) multicenter clinical trial, published in the May 11, 2006, issue of the New England Journal of Medicine, answers a question that pediatricians and researchers have been asking for years: Can medicine that treats the inflammation of asthma be used to prevent the disease if given early enough in at-risk patients?
"Asthma is an enormous public health problem, and this study was designed to see if we could stop the development of asthma in its tracks -- while the lungs are still developing ' in young children known to be at high risk," said NHLBI Director Elizabeth G. Nabel, MD. "Although this study shows that inhaled corticosteroids do not prevent chronic asthma, it provides clear evidence that inhaled corticosteroids benefit even some of our youngest patients."
A breathing disease in which the airways are inflamed, asthma is the most common chronic childhood illness in the United States. In 2004, nearly 9 million children had been diagnosed with asthma, including 1.5 million under the age of 5 years, according to the Centers for Disease Control and Prevention (CDC). In addition, children 4 years old or younger have the highest rates of hospitalization (59 per 10,000) and emergency room use (162 per 10,000) due to asthma of any age group. Overall, CDC estimates that more than 20 million Americans have been diagnosed with asthma.
Researchers have found that in most cases of chronic asthma, symptoms such as frequent coughing, wheezing (a whistling or squeaky sound during breathing) or shortness of breath begin during the first three years of life. Declines in lung function can occur this early as well. However, few studies have been conducted in children under 4 years of age.
In the PEAK trial, 285 children ages 2 to 3 years at high risk for asthma were randomly selected to receive either daily treatment of inhaled corticosteroid treatment (fluticasone propionate [Flovent] 88 mcg twice daily, using a metered-dose inhaler with a valve spacer and mask) or placebo for two years. All children in the study received additional medication to treat symptoms if they occurred. After two years, daily use of inhaled corticosteroids (or placebo) was stopped, and all participants were observed for an additional year to determine if the earlier treatment had lasting effects. Researchers report no significant differences between the participants in the treatment group and participants in the control (placebo) group during this observation period.
"We found that inhaled corticosteroids did not alter the natural course of disease in children who began daily treatment at 2 or 3 years of age," noted Theresa W. Guilbert, MD, lead author of the paper and assistant professor of pediatrics at the Arizona Respiratory Center of the University of Arizona College of Medicine in Tucson. "After a year without treatment, the children who had received inhaled corticosteroids had roughly the same frequency and severity of asthma-related symptoms and similar levels of lung function as the children who had not been treated."
During the two-year treatment period, however, children treated with the daily inhaled corticosteroids had significantly fewer and less severe asthma symptoms than their peers who were given placebo. For example, children treated with inhaled corticosteroids had on average 2 days of symptoms per month compared to 4 days of symptoms per month in the placebo group. They also had a lower rate of severe asthma exacerbations requiring additional treatment with oral corticosteroids and had less need for leukotriene receptor antagonists or additional inhaled steroid treatments.
The researchers found that the inhaled corticosteroids appeared to slow the growth of the children in the treatment group; however, this effect appeared to be temporary. The difference in growth rate was significant between the two groups during the first year of the study, but not during the second year of treatment. During the third-year observation period, the children who had been regularly treated with inhaled corticosteroids grew more quickly than the children who had not received inhaled corticosteroids. Overall, the children in the placebo group grew an average of 1.1 cm more than the children in the treatment group after two years, but by the end of the three-year study, the difference in average increase in height dropped to 0.7 cm.
"Another helpful outcome of the PEAK study is that it demonstrated that the asthma predictive index used in the study can help identify children who are at high risk for asthma-related problems," noted Lynn M. Taussig, MD, chair of the CARE Network, special advisor to the Provost, University of Denver and past president and chief executive officer of National Jewish Medical and Research Center.
The asthma predictive index showed that children at risk are those with frequent wheezing who also have either
"Perhaps the asthma predictive index can be used as a tool to help parents and pediatricians recognize vulnerable children early, in order to begin treatment and help the children have as many symptom-free, active and playful days as possible," said Taussig.
The results of PEAK are similar to a large, five-year study of older children (ages 5 to 12 years), which demonstrated that inhaled corticosteroids are generally safe and effective for children with mild-to-moderate asthma. Like PEAK, the NHLBI-supported Childhood Asthma Management Program (CAMP) showed a slight reduction in growth rate among children taking inhaled corticosteroids only during the first year of treatment. Also like PEAK, the benefits of treatment stopped when the treatment was discontinued.
Guidelines from the National Asthma Education and Prevention Program recommend inhaled corticosteroids or another daily long-term control medication in older children and adults with persistent asthma to prevent symptoms and quick-relief medication such as inhaled bronchodilator to treat acute asthma symptoms if they occur. The results of the PEAK study provide strong support for extending the use of inhaled corticosteroids, for the same reasons, to pre-school children at high risk for asthma.
PEAK was conducted by investigators at National Jewish Medical and Research Center, Denver, CO; University of Wisconsin - Madison; University of California San Diego and Kaiser Permanente, San Diego; Washington University, St. Louis, MO; and University of Arizona College of Medicine, Tucson. The Data Coordinating Center was at the Pennsylvania State University College of Medicine, Hershey, PA.
Medications and devices used in the study were donated by GlaxoSmithKline, Inc., Research Triangle Park, NC; Muro Pharmaceutical, Inc., Tewksbury, MA; Merck & Co., Inc., West Point, PA; Schering-Plough Corporation, Kenilworth, NJ; Lincoln Diagnostics, Decatur, IL; Monaghan Medical, Plattsburgh, NY.
To interview Virginia Taggart, MPH, NHLBI project officer for PEAK, please contact the NHLBI Communications Office at (301) 496-4236. To interview Dr. Guilbert, please contact Liz Beckett, coordinator of community affairs at the Arizona Respiratory Center, University of Arizona, at (520) 626-6387. To interview Dr. Taussig, please contact (303)-871-2815.