EDITORIAL
INHALED CORTICOSTEROIDS?
The appearance in 1972 of beclomethasone dipropionate, the first useful corticoid suitable for administration by inhalation, was undoubtedly a milestone in asthma therapy. To a great extent it made systemic corticosteroid administration, which had been used for years, unnecessary. The important side effects of oral corticosteroids made it necessary to limit their use and to seek strategies for minimizing dosage, such as administering the medication early in the morning or on alternate days, which helps to reduce the suppressive effect of these drugs on the hypothalamic-pituitary-adrenal (HPA) axis. On the other hand, prolonged use of corticosteroid, or reiterated use of corticosteroid cycles lasting several days for the treatment of recurrences of severe episodes of asthma not infrequently lead to corticosteroid dependence, which often have serious consequences.
Neither beclomethasone nor more recent drugs, such as budesonide and fluticasone, are free of risk. Without entering into a discussion of the effectiveness or advantages of different preparations, which is difficult to demonstrate (1) because effectiveness can vary in relation with the inhalation system (2) or with the inhalation technique used (3), all three products can cause undesired effects, including delayed growth, effects on the HPA system, and induction of osteoporosis. There is no doubt that these effects correlate with dosage and duration of treatment. A negative influence on bone growth has been demonstrated for all three corticosteroids cited, with small variations between them (4, 5), a finding that should be kept in mind when these medications are administered to children. Several studies have shown depression of the HPA axis (6, 7), which is an important consideration for patients of any age. Finally, osteoporosis has been examined by many studies, including the study by Harmanci et al. that appears in this number of Allergologia et Immunopathologia (8). Apparently, prolonged administration of corticosteroids by inhalation does not cause bone demineralization in children or adults if the maximum recommended dose is not exceeded because this side effect seems to be more dependent on dose than on duration of treatment (9, 19). However, sustained treatment (3 to 8 years) of children 4 to 11 years old with a minimum dose of 400 µg/day of budesonide or beclomethasone has been found to cause a reduction in bone mineral density (11).
Therefore, the true need for these medications should always be weighed, as well as the maximum safe effective dosage and the planned duration of treatment (12). In Spain, the use of inhaled corticosteroids is on the rise in primary care centers, to the extent that we believe that they are being used excessively, for everything from mild episodes of respiratory difficulty to asthma attacks and prolonged coughing. Sometimes doses are excessive and there is no control over duration of treatment, and it is not unusual for these medications to be administered for months. Therefore, it should be kept in mind that the main use of inhaled corticosteroids is to reduce inflammation. According to consensus studies (13, 14), inhaled corticosteroids should be reserved for the treatment of moderate to severe asthma, and maximum dosage for budesonide or beclomethasone should not exceed 400 µg/day in children or 800 µg/day in adults; fluticasone is administered at half these dosages. This dosage should be increased only exceptionally, not only as a way of preventing side effects but also because effectiveness does not seem to be dose-dependent. Treatment should conclude when therapeutic goals are attained, that is, when the frequency and intensity of episodes and inflammation have been reduced, as confirmed by strict control of respiratory function or the use of invasive techniques to study cellularity and the mediators of the inflammatory reaction. Another problem is the optimal age for beginning prolonged treatment with these medications can be considered. Although this always depends on the patient''s condition, there seems to be consensus in accepting this treatment in children four years and older, if an indication exists (15).
Therefore, the answer to the question "Inhaled corticosteroids? is definitely "yes", as long as indications and doses are strictly observed.
F. Muñoz-López
REFERENCES
1.Kamada AK, Szefler SJ. Editorial. How should inhaled glucocorticoids be compared? J Allergy Clin Immunol 1997;99:735-7.
2.Agertoft L, Pedersen S. A randomized, double-blind dose reduction study to compare the minimal effective dose of budesonide Turbuhaler and fluticasone propionate Diskhaler. J Allergy Clin Immunol 1997;99:773-80.
3.Gracia-Antequera M, Morales MM. An intervention to improve the inhalatory technique of children and adolescents with asthma. Allergol et Immunopathol 1999;27:255-60
4.Saha MT, Laippala P, Lenko HL. Growth of asthmatic childen is lower during than before treatment with inhaled glucocorticoids. Acta Pediatr 1997;86:138-42.
5.Aller BD. Influence of inhaled corticosteroids on growth: a pediatric endocrinologist''s perspective. Acta Pediatr 1998;87:123-9.
6.Clark DJ, Clark RA, Lipworth BJ. Adrenal suppression with inhaled budesonide and fluticasone propionate given by large volume spacer to asthmatic children. Thorax 1996;51:941-3.
7.Todd G, Dunlop K, McNaboe J, et al. Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate. Lancet 1996;348:27-9.
8.Harmanci E, et al. The comparison of the effects of fluticasone propionate and budesonide on clinical indices and bone mineral density in the asthmatic patients: a one year treatment study. Allergol et Immunopathol 1999;27:298-303.
9.Toogood JH, Baskerville JC, Markov AE, Hodsman AB, Fraher LJ, Jennings B, et al. Bone mineral density and the risk of fracture in patients receiving long-term inhaled steroid therapy for asthma. J Allergy Clin Immunol 1995;96:157-66.
10.Tangsinmankong N, Bahna SL, Good RA. Osteoporosis for the allergist. Ann Allergy Asthma Immunol 1999;82:5-14.
11.Boot AM, Jongse JC, Verbene AAPH, Pols HAP, Muinck Keizer-Schrama SMPF. Bone mineral density and bone metabolism of prepuberal children with asthma after long-term treatment with inhaled corticosteroids. Pediatr Pulmonol 1997;24:379-84.
12.Muñoz-López F. Alergia respiratoria en la infancia y adolescencia. Barcelona. 2ª ed.: Springer-Verlag; 1999.
13.National Institute of Health. Guideline for Diagnosis and Management of Asthma. Draft. Meeting of the American Academy of Asthma. Allergy and Immunology 1997.
14.Warner JO, Naspitz CK (editors). Third International Pediatric Consensus Statement on Management of Childhood Asthma. Pediatr Pulmonol 1998;25:1-17.
15. Pedersen S, Warner JO, Price JF. Early use of inhaled steroids in children with asthma. Clin Exp Allergy 1997;27:995-1006.
