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 http://www.nih.gov.
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