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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.