Significant variability in response to inhaled corticosteroids for persistent asthma

Stanley J. Szefler, Richard J. Martin, Tonya Sharp King, Homer A. Boushey, Reuben M. Cherniack, Vernon M. Chinchilli, Timothy J. Craig, Myrna Dolovich, Jeffrey M. Drazen, Joanne K. Fagan, John V. Fahy, James E. Fish, Jean G. Ford, Elliot Israel, James Kiley, Monica Kraft, Stephen C. Lazarus, Robert F. Lemanske, Elizabeth Mauger, Stephen P. PetersChristine A. Sorkness

Research output: Contribution to journalArticle

Abstract

Background: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. Objective: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. Methods: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV1 and PC20; risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 μg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 μg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 μg/day. Results: Maximum FEV1 response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC20 improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV1 response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV1/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC20, in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years). Conclusions: Near-maximal FEV1 and PC20 effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.

Original languageEnglish (US)
Pages (from-to)410-418
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume109
Issue number3
DOIs
StatePublished - Jan 1 2002

Keywords

  • Asthma
  • Beclomethasone dipropionate
  • Exhaled nitric oxide
  • Fluticasone propionate
  • Inhaled corticosteroid
  • Methacholine response
  • Pulmonary response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Szefler, S. J., Martin, R. J., King, T. S., Boushey, H. A., Cherniack, R. M., Chinchilli, V. M., Craig, T. J., Dolovich, M., Drazen, J. M., Fagan, J. K., Fahy, J. V., Fish, J. E., Ford, J. G., Israel, E., Kiley, J., Kraft, M., Lazarus, S. C., Lemanske, R. F., Mauger, E., ... Sorkness, C. A. (2002). Significant variability in response to inhaled corticosteroids for persistent asthma. Journal of Allergy and Clinical Immunology, 109(3), 410-418. https://doi.org/10.1067/mai.2002.122635