Inhaled Corticosteroids Benefit Young Children with Frequent
Wheezing but Do Not Prevent Development of Chronic Asthma
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
- one of the following: eczema (a chronic skin disease characterized by itchy,
inflamed skin), allergic reactions to airborne substances such as dust mites,
or a parent with asthma; OR
- two of the following: food allergy, wheezing unrelated to colds, or elevated
levels of eosinophils (a type of white blood cell).
"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.
Resources
Part of the National Institutes of Health, the National Heart, Lung, and
Blood Institute (NHLBI) plans, conducts, and supports research related to the
causes, prevention, diagnosis, and treatment of heart, blood vessel, lung,
and blood diseases; and sleep disorders. The Institute also administers national
health education campaigns on women and heart disease, healthy weight for children,
and other topics. NHLBI press releases and other materials are available online
at: www.nhlbi.nih.gov.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit www.nih.gov. |
