---

Dr. Brown is an assistant professor of pharmacy practice at Palm Beach Atlantic University, Lloyd L. Gregory School of Pharmacy, Palm Beach, Florida.

---

Asthma—a condition associated with chronic inflammation, bronchial hyperresponsiveness, and typically reversible bronchospasms— affects children more commonly than adults. The illness leads to missed days at school, frequent emergency department (ED) visits, a reduction in quality of life, increased health care costs, and even death.^1,2 In 2004, 6.2 million children <18 years of age were reported to have asthma, and, of these, 3.9 million children had an asthma attack.³

The highest prevalence of asthma occurs in children aged 5 to 17 years, and ~40% of children who have parents with asthma will develop the condition. In addition, the rate of asthma occurring in children <5 years old increased by more than 160% from 1980 to 1994.^3,4

Despite these alarming statistics, appropriate treatment, monitoring, and patient education can control asthma and its symptoms and allow patients to live fully active lives.

The Role of Corticosteroids

Because inflammation is a hallmark finding in patients with asthma, the use of corticosteroids is a rational treatment option to minimize deleterious effects on the lungs. The use of these drugs in pediatric patients, however, is a common concern among health care providers and parents, particularly with regard to their adverse-event profile.

Frequent concerns relate to a reduction in the rate of linear (ie, vertical) growth and bone mineral density. The risk for these adverse effects is greater in patients receiving systemic corticosteroids, as opposed to inhaled corticosteroids (ICSs). Nonetheless, concern remains regarding the safety of ICSs in children.

In the Childhood Asthma Management Program study, which included 1041 children aged 5 to 12 years with mild-tomoderate asthma, those receiving inhaled budesonide experienced a delay in linear growth of about 1.1 cm during the first year of therapy, compared with those receiving nedocromil or placebo. Growth velocity was similar in all groups during subsequent years of treatment, however. In addition, bone mineral density of the lumbar spine was not reduced in the patients receiving ICS therapy.⁵

Overall, ICSs may decrease the shortterm linear growth rate in children, but the effects are small and may be partially reversible. ICS therapy does not appear to be associated with sustained reductions with continued treatment.^5-7 Additionally, the effect on linear growth does appear to be dose-related, with the highest potential associated with highdose ICS therapy.

ICSs are associated with far fewer adverse effects, however, when compared with systemic corticosteroids, especially for the treatment of severepersistent asthma.⁸

In the Expert Panel Report 3, the National Asthma Education and Prevention Program continues to recommend ICSs for the management of mildpersistent, moderate-persistent, and severe-persistent asthma as the most effective maintenance therapy.⁸ To minimize systemic absorption of ICSs and ultimately to reduce the risk for these adverse effects as well as oral thrush, patients should be counseled to rinse with water and spit following the administration of ICSs. The use of devices such as spacers and valved holding chambers also have been shown to reduce the risk for oral candidiasis.⁸

Albuterol Versus Levalbuterol in Pediatric Patients

Short-acting beta₂ agonists such as albuterol and levalbuterol are used frequently in acute exacerbations, especially in the ED, to quickly alleviate bronchospasms. Albuterol is a 50:50 racemic mixture of the R- and S-enantiomers, whereas levalbuterol consists only of the R-enantiomer, which is responsible for bronchodilation. In addition, levalbuterol has a greater binding affinity to the beta₂ receptor to produce its bronchodilator effects. Airway reactivity associated with albuterol use is attributed to the S-enantiomer in the racemic mixture—which is the reason why levalbuterol was developed.⁹

Because of the increased expense associated with levalbuterol, experts have raised questions regarding its efficacy, compared with that of albuterol. In 1 study, 129 children between 2 and 14 years old, who were seen in the ED for acute moderate or severe asthma attacks, were given weight-based doses of albuterol or levalbuterol via nebulizer for 5 treatments, along with oral systemic corticosteroids following the second dose and ipratropium following the third dose. The researchers noticed no differences between the 2 groups with regard to clinical asthma scores, hospitalization rates, or pulmonary-function test results.¹⁰

Another study with children aged 1 to 18 years, seen in the ED for acute asthma exacerbations, found that those treated with levalbuterol had fewer hospitalizations, compared with those who were treated with albuterol (36% vs 45%, respectively). The length of hospital stay, however, was not significantly different between the 2 groups.^11,12

Although the findings from these studies are mixed, appropriate administration of a short-acting beta₂ agonist, either albuterol or levalbuterol, during an acute asthma exacerbation is most critical to reduce morbidity and mortality.

Administration Technique

Medications used in the management of asthma are available in various devices, including metered dose inhalers (MDIs), dry-powder inhalers (DPIs), and nebulizers. Pediatric patients may be reluctant to use these devices or may experience difficulty when trying to use them appropriately. Proper inhalation technique is vital to ensure adequate drug delivery and to minimize adverse drug reactions. A table listing the steps for appropriate use of MDIs can be found here.

Solutions given via nebulizers may be a better option for younger patients who have difficulty maneuvering devices, because nebulizers do not require significant manual coordination while being administered. The disadvantages of using nebulizers may include a longer period of time to receive treatment, as well as inconvenience, because these devices are not as easily transported from home to school or day care, compared with other devices.

MDIs may be difficult for pediatric patients to actuate appropriately using hand-breath coordination. To increase medication delivery to the lungs, spacers or valved holding chambers may be recommended, because these devices "hold" the dose of medication to allow the patient more time to inhale appropriately.

Pharmacist's Role

Pharmacists can play a vital role in the management of pediatric patients with asthma. Patient education, especially regarding appropriate inhalation technique, is essential to ensure adequate medication delivery. Providing handouts with pictures of appropriate inhaler technique, as well as asking patients to demonstrate technique after proper instruction, may be useful, particularly with children.

Recommendations regarding the use of spacers, valved holding chambers, or face masks may be necessary for pediatric patients who have difficulty with manual coordination of MDIs. In addition, patients who frequently refill shortacting beta₂ agonists such as albuterol (ie, >1 canister every 1-2 months) may be candidates for referral to their primary care physicians, because frequent use of quick-relief medications (ie, >2 days per week for symptom relief) is typically considered an indicator of poorly controlled asthma. Regular use of shortacting beta₂ agonists also is associated with an increased risk for asthma exacerbations.⁸

Emphasis on daily administration of controller medications such as ICSs is important to reduce the risk for asthma attacks. Refill reminders on maintenance medications may increase patient adherence, as some patients may discontinue treatment because they have no symptoms.

Pharmacists may be asked by concerned parents or caregivers about the impact of ICS therapy on linear growth. Proper education about the minimal risks versus the potential benefits of therapy may be warranted. It is important to emphasize that, even though ICS therapy may impact linear growth slightly, there also is a risk for delayed growth in children who have poorly controlled asthma.⁸ Methods to minimize systemic absorption (ie, rinsing with water and spitting after administration and spacer usage) also may be provided.

In addition, pharmacists may be involved in the development of written asthma action plans in conjunction with patients' physicians. These action plans provide steps to be taken based on lung function, which is determined from peakflow meter readings and which helps detect the onset of an asthma attack, even if the patient is feeling well. Written asthma action plans are especially important for those patients who have moderate- to severe-persistent asthma or who have a history of poorly controlled asthma. Development of a written asthma action plan for school also may be warranted.⁸

Increasing awareness of special considerations for pediatric patients with asthma can help improve quality of life, decrease health care costs, maximize functional capacity, and prevent deaths.

References

1. Williams D. Strategies for optimizing treatment of acute and chronic asthma. Introduction: asthma epidemiology and economic impact. Am J Health Promot. 2006;63(10 suppl 3):S3-S4.
2. Schreck DM. Asthma pathophysiology and evidence-based treatment of severe exacerbations. Am J Health Promot. 2006;63(10 suppl 3):S5-S13.
3. American Lung Association. Trends in asthma morbidity and mortality. American Lung Association Web site. www.lungusa.org/atf/cf/~ASTHMA06FINAL.PDF. Accessed September 20, 2007.
4. American Academy of Asthma, Allergy and Immunology. Asthma statistics. www.aaaai.org/media/resources/media_kit/asthma_statistics.stm. Accessed February 5, 2007.
5. Kelly HW, Strunk RC, Donithan M, et al. Growth and bone density in children with mild-moderate asthma: a cross-sectional study in children entering the Childhood Asthma Management Program (CAMP). J Pediatr. 2003;142:286-291.
6. Leone FT, Fish JE, Szefler SJ, West SL. Systematic review of the evidence regarding potential complications of inhaled corticosteroid use in asthma. Chest. 2003;124:2329-2340.
7. Witzmann KA, Fink RJ. Inhaled corticosteroids in childhood asthma. Drugs 2000;59(suppl 1):9-14.
8. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and Management of Asthma. National Heart, Lung, and Blood Institute Web site. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed September 20, 2007.
9. Pleasants RA. Focus on inhaled beta2 agonists: efficacy, safety and patient preference. Pharmacotherapy. 2004;24(5 pt 2):44S-54S.
10. Qureshi F, Zaritsky A, Welsh C, Meadows T, Burke BL. Clinical efficacy of racemic albuterol versus levalbuterol for the treatment of acute pediatric asthma. Ann Emerg Med. 2005;46:29-36.
11. Carl JC, Myers TR, Kirchner HL, Kercsmar CM. Comparison of racemic albuterol and levalbuterol for treatment of acute asthma. J Pediatr. 2003;143:731-736.
12. Blake K. Review of guidelines and the literature in the treatment of acute bronchospasms in asthma. Pharmacotherapy. 2006;26(9 pt 2):148S-155S.