Significant variability in response to inhaled corticosteroids for persistent asthma

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• 作者：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
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2002
• 出版时间：March 2002
• 年：2002
• 卷：109
• 期：3
• 页码：410-418
• 全文大小：515 K

文摘

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. (J Allergy Clin Immunol 2002;109:410-8.)