Use of Inhaled Corticosteroids in Children

Inhaled corticosteroids are the single best treatment for inflamed airways in asthma. Studies from both younger and older pediatric age groups show reduction in asthma symptoms, and improved exercise tolerance and many other factors in children using regular ICS.

The C.A.M.P. trial (New Engl J Med 2000, 343:1054-63 - level 1 evidence) looked at 1041 children, aged 5 - 12 years with mild to moderate asthma. These children were treated with either budesonide 200 mcg twice daily or placebo or nedocromil (a mast cell stabilizer). Only the budesonide group showed significant improvement in pulmonary function over time. In addition, patients on the ICS demonstrated decreased hospital utilization, fewer courses of oral prednisone, a greater number of episode-free days, significant improvement of symptoms and less p.r.n. salbutamol use.

In the younger age group, the PEAK trial was recently published (Guilbert et al, New Engl J Med 2006; 354:1985-97 - level 2 evidence). Children age 2 - 3 years, who were at high risk for developing asthma, were treated with regular fluticasone or placebo for two years. Medication was stopped after one year of observation. There was a significant proportion of episode-free days in the group receiving the inhaled corticosteroids compared to the placebo group. Once the medication was stopped, symptoms returned to baseline and were similar to the placebo group. Inhaled corticosteroids did not result in any long term changes in the airways or change in the course of the disease.

There is no evidence that intermittent use of inhaled corticosteroids for intermittent wheezing has any effect on symptoms and does not result in delayed persistent wheeze (Bisgaard et al, New Engl J Med; 354:1998-2005 - level 1 evidence). In this study, for children at high risk of asthma, 14-day treatments of budesonide or placebo, after 2 - 3 days of wheezing, did not result in reduction of symptom-free days or had any other impact on the episodes during the first 3 years of life.

Autoscaling

The Canadian Pediatric Asthma Consensus Guidelines have promoted the concept of "autoscaling" when prescribing ICS.(Becker et al, CMAJ 2005). In general, this means that smaller children have smaller lungs, smaller total volumes and, therefore, will inhale smaller amounts of medication when delivered by an MDI and aerochamber, or dry powder device. The recommendation is that a standard dose of inhaled corticosteroid should be given despite the patientÕs age. One of the best studies looking at this compared a dose of 400 mcg of budesonide administered by metered dose inhaler and aerochamber to 2 - 3 year olds, 4 - 6 year olds and adults. Despite the varying ages, plasma concentrations (a direct reflection of inhaled dose) over time were exactly the same (Anh¿j et al, Am. J. Respir. Crit. Care Med., 62; 2000:1819-1822 0.

Safety Issues

There are two issues with regards to safety of inhaled corticosteroids, especially with regards to growth. In the short term, there is a statistically significant reduction in growth velocity when an inhaled corticosteroid therapy is started. Within 2 - 3 months, the growth velocity becomes similar to that of placebo. Studies have shown no significant impact on long-term growth (Agertoft & Pederson, N Engl J Med 2000; 343:1064-1069 - level 2 evidence). Inhaled corticosteroids have no effect on the immune system. Chronic uncontrolled lung inflammation will lead to lung remodeling with resulting fibrotic changes.

Parents need to understand that the reason for using inhaled corticosteroids is to control the inflammation, which, in the long run, will reduce symptoms and prevent remodeling.

Another issue of safety that is often raised by patients (although not usually in the pediatric age group) is that of the risk of osteoporosis. There are many conflicting studies looking at the use of long term inhaled corticosteroids for asthma and their effect on bone density. One of the problems is with the design of the studies. Many studies are small or do not take into account the severity of the disease, use of oral steroids or the activity level of the patient. Some do not separate the subset of patients with chronic obstructive lung disease. A Cochrane Review on the effects of inhaled steroids on bone metabolism concluded that in patients with asthma or mild COPD, there is no evidence of an effect of inhaled corticosteroids on BMD or vertebral fractures when given at conventional doses for 2-3 years. Higher doses were associated with biochemical markers of increased bone turnover, but data on BMD and fractures at these higher doses are not available.

The length of time a patient should be using ICS depends on the pattern of symptoms that the child manifests. Usually, the patient should attain 6 months of adequate to complete control before discontinuing the medication. If the symptoms are worse during specific times of the year (Winter for example), continuous use during that time, with discontinuation at other times of the year may be appropriate.

During an acute exacerbation of the disease the dose of ICS can be increased and once the symptoms are controlled, the dose can be reduced to the previous level.

- Alan Kaplan

Thanks to Dr. Andrew McIvor for reviewing the draft copy of this article. Thanks to Dr. Andrew McIvor for reviewing the draft copy of this article. Dr. McIvor is Professor of Medicine McMaster University, Staff Respirologist Firestone Institute for Respiratory Research St Joseph's Healthcare Hamilton, Ontario.

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