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Corticosteroid Treatment in Pediatric Asthmatics
Jessica Farmer
Research in Allied Health
Abstract
Asthma is a chronic respiratory problem that affects about 1 out of 4 American
citizens, and it is estimated that there are about 9 million children under the age of 18 that
have been diagnosed with asthma according to the American Lung Associations. Asthma
causes constriction and inflammation of the airways with increased production of mucus
making it hard for the person to breathe. Inhaled corticosteroids suppress airway
inflammation, and are effective in controlling asthma in children. Even though this is
seen as true, the use of inhaled corticosteroids has been debated due to the side effects
they could possible cause. A major concern lies with the idea that these drugs could stunt
a child’s growth. This research looks into whether inhaled corticosteroids truly stunt a
child’s growth if taken long-term, thus helping decide whether inhaled corticosteroids
should be retained as a drug of choice in treating pediatric asthma.
Problem statement
In this study, I am going to try to prove that corticosteroid treatment of asthmatic children
does not cause growth suppression whether male or female.
Introduction
Asthma is the most common chronic disorder in childhood, currently affecting 6.8
million children under 18 years of age (American Lung Association). Asthma is a Greek
word which means to breathe hard.
“It is a condition of altered dynamic state of
respiratory passages due to the action of diverse stimuli resulting in airways obstruction
of varying degree and duration, and reversible partially or completely spontaneously or
under treatment” (Kuzemko, 1). One means of treatment is corticosteroids which were
isolated by Tadeusz Reichstein in 1936, and was first synthesized by Lewis H. Sarett in
the 1950’s. It is a drug that is synthesized from cholesterol from the adrenal cortex and
blocks the inflammation caused by asthma. Corticosteroids can be administered topically,
orally, or through inhalation, but for the purposes of this research there will be a focus on
inhaled corticosteroids. Although it has shown to be an effective treatment in both adults
and children; some believe that it may cause suppression of growth in children.
Review of Literature
There are multiple forms of inhaled corticosteroids that include: budesonide,
fluticasone propionate, flunisolide, and triamcinolone among others, and dependent on
the specific ones, they can be administered via inhalation, oral, or topically. With review
of multiple studies, the most safe and effective means of administering corticosteroids is
inhalation. “Inhaled corticosteroids are recommended as first-line therapy for persistent
asthma in children as well as adults” (Allen 2002, 208). “The exact mechanism of action
of corticosteroids in pulmonary diseases is not well defined” (Benedictis 1996, 44).
“Anti-inflammatory and immunosuppressive properties may by due to their inhibitory
effect on cytokine expression and effects, thus blocking the interaction between the cells
of the immune system” (Benedictis, 44). The Benedictis study also states that one week
of treatment with corticosteroids can reverse the seasonal increase in airway reactivity in
patients with grass pollen allergy. There are different severities of asthma, and as a child
grows the severity will either increase or decrease. “Disease severity may also affect the
relationship between therapeutic and systemic effects. The observation that doses of ICS
causing growth suppression in children with mild-moderate disease do not slow growth
when administered to some severely affected patients supports greater deposition and
absorption of drug via less obstructed airways” (Allen 209).
“Numerous studies have established that inhaled corticosteroids (ICSs) improve
pulmonary function, reduce the need for reliever medications, improve quality of life,
improve exercise tolerance, and reduce hospitalization rates in children with asthma of all
ages”(Berger 2004, 387). The National Asthma Education and Prevention Program
(NAEPP) has included ICS in guideline recommendations for children 5 year and under.
The most effective means of administration for children less than 5 years of age is the
nebulizer which does not require hand or respiratory coordination, although intake of
nebulized medication is affected by the device used, its flow rate, the drug concentration,
formulation & viscosity, and the patient’s tidal breathing.
The next administration
method that is recommended is the pressurized metered dose inhaler with spacer although
not recommended for patients who are under 4 years of age. Budesonide inhalation
suspension was the first ICS formulation, and the only one to date, to be approved in the
United States for jet nebulizer use in the treatment anti-inflammatory symptoms of
asthma in children 12 months to 8 years of age, and its efficacy was proved through
studies in the United States, Europe, and Israel (Berger 2004, 389).
Through the
nebulizer the medication is diluted with a saline or can be mixed with albuterol,
cromolyn, or fenoterol among a few others in order to create optimal effects in the
treatment of childhood asthma (Berger 392). ICS administration proved to be effective in
reducing the number of days and nights a child went without symptoms. “Long-term
safety study of budesonide that included children as young as 2 years with severe
persistent asthma demonstrated no effect with 3 to 5 years of treatment with budesonide,
on HPA axis function measured by concentrations of pre-stimulation and post-stimulation
corticotrophin
plasma
cortisol,
24-hour
serum
cortisol,
and
urinary cortisol
excretion”(Berger 394). There was a slightly higher incidence of contact dermatitis
found, and the most frequently reported adverse effects included respiratory infection,
otitis media, rhinitis, and sinusitis. There were not significant differences in growth or
height velocity or standard height between ICS and other asthma therapies. “The benefits
of ICS treatment generally outweigh the potential risks, and a more favorable cost-benefit
ratio is particularly apparent for treatment of more severe asthma with these agents.
Further reduction of risk is possible by titration to the lowest effective dose” (Berger
369).
The adverse effect of growth suppression is due to “inhibited intestinal calcium
absorption, increase urinary calcium excretion, and promote bone resorption, all of which
can negatively affect bone formation and growth.
Small amounts of exogenous
corticosteroid in excess of normal physiologic requirements are capable of suppressing
childhood growth” (Allen 211). Most of the studies that have been reviewed have found
regulation of doses based on the individual decreases these effects.
A study by Szefler (2004) states, “Despite evidence supporting the efficacy of
ICU therapy in pediatric patients, under use of ICS’s in the United States has been
documented” (83). A major concern with corticosteroids is the adverse effect of growth
suppression in children.
Bahceciler’s (2002) study states “many asthmatic children
experience pre-pubertal growth retardation and delayed onset of puberty,” and in this
study there was an insignificant correlation between ICS treatment and bone mineral
density and AP spine measurements.
The Moudiou (2003) study found, “As a group, asthmatic children were no
different than their healthy peers with respect to both height and weight”(669), although
pubertal asthmatic girls were found to be significantly shorter than their control
counterparts.
“A probable explanation was that they presented delay in pubertal
maturation, a phenomenon well-described in asthmatic children”(669).
ICSs are also effective when used in combinations with other medications. The
combination of fluticasone propionate (FP) and salmeterol (SA) show a reduction in
rescue albuterol use compared to FP alone and shows no safety risks. Efficacy was
measured by the individual’s progress by comparing the number of emergency room
visits, hospitalizations, and severity of asthma before and during combination therapy.
With use of the combination, emergency room visits, hospitalization, and frequency of
wheezing were all reduced (Sekhsaria 2004, 579). A study by Carroll (2006) found
similar results and stated, “studies in children have linked the use of chronic ICS to
decreased hospitalization for asthma…these studies are consistent with studies of adult
patients
with
asthma
that
have
linked
ICS
use
with
decreased
risk
of
hospitalization”(Carroll 1215).
While the other studies discussed have shown insignificant occurrences of the
adverse effects, the study by Anthracopoulos (2007) had some significant findings that
differed from the rest. The test group used for this study came in for at least five visits in
order to measure differences in height, weight, and efficacy of treatment. On the first
visit, baseline data was collected. On the second and third visits they found a decrease in
height standard deviation score, but adversely on the fourth and fifth visits there was an
increase in height standard deviation score. “It (height) was adversely affected mostly
during the first 6 months but was compensated for after the first 12 months of treatment.
Catch-up growth was observed during the second and third year of treatment”(468).
They found no differences in the variables: height standard deviation, height velocity
standard deviation, and body mass index standard deviation between the different
treatments: budesonide or fluticasone propionate (Anthracopoulos 466). In the same
aspect “the effect of inhaled corticosteroids on linear growth and ultimate height may be
different in early childhood due to the rapid somatic growth during this period of human
development” (Kaditis 2003, 248).
Methods
The proposed study is to assess the effects of use of inhaled corticosteroids in
pediatrics patients. The sample population would come from pediatric wings of area
hospitals. The criteria for participation would be: patients who are 4 to 17 years of age
who have moderate to severe asthma without any other chronic diseases.
Before anything begins, the study methods and scale of measure would be
submitted to East Tennessee State University IRB, once passed the research process
would continue.
HIPPA regulations would be followed, and written, informed consent would be
obtained from the parents in order to review the patient’s history and conduct pre- and
posttests, lab work and physical exams that would include using strategically compiled
surveys given to the parents about changes in their child’s symptoms and behaviors,
obtaining the child’s height before treatment and periodically during and after the
treatment is given. Threats to validity and reliability were addressed.
Study protocol would follow the one done by Berger and Shapiro (2004) who
completed an open-label study of 257 participants who were treated with fluticasone,
50μg or 100μg twice daily via Diskhaler. Adverse effects were seen in 10% of patients
(n=26). The trial was extended in the same open-label fashion where 192 patients were
re-randomized and given 200μg once daily or 100μg twice daily. In this extension,
adverse effects occurred in 4-6% of patients in each group. No significant differences in
height velocity adjusted for age and sex or height standard deviation scores adjusted for
sex were observed between patients who received fluticasone (n=34) or cromoglycate
(n=26) for the year duration. While the first 2 groups and the second 2 groups could be
compared separately using the T-test for independent samples, all four groups’
measurements of adverse effects would be compared using the analysis of variance under
a parametric, interval data.
Results/Discussion
The data showed that the children treated with fluticasone 200μg per day had
significantly (P=.002) fewer days and nights without symptoms than those who received
the placebo. The medication related adverse effects were seen in 10% (n= 26) patients.
Of these, 8 have asthma related events, 4 experienced hoarness, 4 had oral candidiasis, 2
had a cough, and 2 had throat problems.
There was no significant difference found in height velocity of the children in the
study adjusted for age and sex were observed. The urinary function was tested and
showed minimal adrenal effects with the dry powder inhalers. 36% of patients had
abnormal morning cortisol levels. Overall, each of the four groups tolerated inhaled
corticosteroid treatment well.
Conclusion
Inhaled corticosteroids have been proven as an effective suppressor of airway
inflammation in both adult and pediatric patients. The reason they are not prescribed as
often as they could be is due to the idea that a side effect in children is growth
suppression. The literature reviewed along with this study show that there is not a
significant difference between the growth rate and or height velocity of asthmatic
children who receive daily doses of inhaled corticosteroids as opposed to other symptom
controlling drugs.
References
Allen, David B. (2007). Safety of Inhaled Corticosteroids in Children. Pediatric
Pulmonology, 33, 208-220.
Anthracopoulos, Michael B., Anastasios Papadimitriou, Demosthenes B. Panagiotakos,
Garyfalia Syridou, Eleni Giannakopoulou, Andrew Fretzayas, Polyxeni
Nicolaidou, Kostas N. Priftis (2007). GrowthDeceleration of Children on Inhaled
Corticosteroids Is Compensated for After the First 12 Months of Treatments.
Pediatric Pulmonology. 42. 465-470.
Bahceciler, (2002). Inhaled Corticosteroids & Bone Density of Children with Asthma.
Journal of Asthma. 39. 151-157.
Benedictis, Fernando M., Gerard J. Canny, Henry Levison (1996). The Role of
Corticosteroids in Respiratory Diseases of Children. Pedicatric Pulmonology. 22.
44-57.
Berger, William E., Gail G. Shapiro (2004). The use of inhaled corticosteroids for
persistent asthma in infants and young children. Annals of Allergy, Asthma, and
Immunology. 92. 387-400.
Carroll, Christopher L., Anita Bhandari, Craig M. Schramm, Aaron R. Zucker (2006).
Chonic Inhaled Corticosteroids Do Not Affect the Course of Acute Severe
Asthma Exacerbations in Children. Pediatric Pulmonology. 41. 1213-1217.
Kaditis, Athanasios G., Konstantinos Gourgoulianis, Glenna Winnie (2003). AntiInflammatory Treatment for Recurrent Wheezing in the First Five Years of Life.
Pediatric Pulmonology. 35. 241-252.
Moudiou, (2003). Growth of Asthmatic Children Before Long-Term Treatment with
Inhaled Corticosteroids. Journal of Asthma. 40. 667-671.
Sekhsaria, (2004). Efficacy and Safety of Inhaled Corticosteroids in Combination with a
Long-Acting Beta2-Agonist in Asthmatic Children Under Age 5. Journal of
Asthma. 41. 575-582.
Szefler, Stanely J., Ewa Lyzell, Sherahe Fitzpatrick, Mario Cruz-Rivera (2004). Safety
prorfile of budesonide inhalation suspension in the pediatric population:
worldwide experience. Annals of Allergy, Asthma, and Immunology. 93. 83-90.