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COMMENTARY |
Department of Pediatrics
Allergy/Immunology Section
Louisiana State University Health Sciences Center
Shreveport, LA 71130-9323
Abbreviations: ICS, inhaled corticosteroid • HPA, hypothalamic-pituitary-adrenal
As inflammation became recognized as a major component of the pathology of asthma, inhaled corticosteroid (ICS) evolved as the cornerstone for pharmacologic control of the disease. The reward was reduction in asthma morbidity and mortality.1 Nevertheless, pediatricians maintained a concern about the effect of long-term use on growth. Conflicting findings were reported by studies that differed in one or more aspects, eg, the study design, patients’ age, initial severity of asthma, concomitant use of other medications, and degree of asthma control. Even more important is the ICS pharmacologic properties: dose, duration, and delivery system. It is important also to consider the method of assessing the potential adverse effects of ICS. Should the concern be about the growth velocity or the ultimate adult height? The ultracritical investigator may even be concerned about the hypothalamic-pituitary-adrenal (HPA) axis function.
In this issue of Pediatrics, Bacharier et al2 report on the effect of long-term administration of an ICS preparation on the HPA axis function in children with mild to moderate persistent asthma. The study was prospective, for 36 months, on children 5 to 12 years old who received continuous therapy with budesonide Turbuhaler (400 µg/day), inhaled nedocromil (16 mg/day), or inhaled placebo. At 12 and 36 months, the HPA axis function was assessed by the adrenocorticotrophic hormone (ACTH) stimulation test, which revealed 3 major findings. First, the 3 treatment groups did not differ in the cortisol level rise. Second, children who received short courses of prednisone during the 6-month screening period had low cortisol levels at the baseline visit. Third, the test showed a suboptimal response in 4 children (2 in the nedocromil group and 2 in the placebo group), indicating that sporadic "abnormal" responses to the ACTH stimulation do occur even in the absence of corticosteroid intake.
Although these findings may not be extrapolated to other ICS preparations, higher doses, or longer periods, a modest increase in either of the 2 latter variables, if needed, would be favored over poorly controlled asthma. In routine clinical practice, perhaps the prevailing low rate of compliance with long-term use of ICS and the high rate of poor delivery technique are a sort of blessing in disguise!
In a study on prepubescent children with asthma,3 the group as a whole was found to have a diminished growth velocity before starting ICS therapy. After the use of ICS for 5 years, the growth velocity improved in the children whose asthma was controlled. A similar finding was noted by another study in children who received budesonide 600 µg/day for 22 months.4 Although some short-term studies showed a suppressive effect of ICS on growth, a normal adult height is expected.5–7
It is worth noting that individual patients vary in their clinical response to ICS. In patients not responding well to medium doses of ICS, higher doses rarely improved the pulmonary function.8 They may improve by adding a leukotriene receptor antagonist9 or a long-acting inhaled ß-adrenergic agonist for a limited period.10 It also is worth noting that ß-adrenergic agonists are not antiinflammatory. Whenever high doses of ICS are useful, once a satisfactory control is attained for a few months, the dose should be reduced gradually. Prolonged use of high doses should be associated with monitoring for side effects. Glucocorticoid resistance has been described in some severe asthmatics.11
The chlorofluorocarbon-containing metered-dose inhalers are about to be discontinued, and hydrofluoroalkane-based inhalers are being produced, providing a much smaller particle size (1.1 µm) that can reach the small airways in which inflammation is substantial. Patients who were taking chlorofluorocarbon-beclomethasone could be switched to the hydrofluoroalkane preparation at half the dose without worsening of their asthma.12 The recent availability of anti-immunoglobulin E (omalizumab) therapy has been a valuable addition to the armamentarium for allergic asthma control.13
The most effective guard against the need for high doses or multiple medications remains to be the control of provocative factors, eg, specific allergens, irritants, chronic sinusitis, and gastroesophageal reflux. Immunotherapy would be useful in selected patients with aeroallergen sensitivity.
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FOOTNOTES |
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Address correspondence to Sami L. Bahna, MD, DrPH, Department of Pediatrics, Louisiana State University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130-9323. E-mail: sbahna{at}lsuhsc.edu
Dr Bahna is a member of the speakers’ bureaus of AstraZeneca, Aventis, Genentech/Novartis, GlaxoSmithKline, Merck, Pfizer, Sepracor, and UCB Pharma.
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