Significant variability in response to inhaled corticosteroids for persistent asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:109

Article

Szefler, SJ ; Martin, RJ ; King, TS ; Boushey, HA ; Cherniack, RM ; Chinchilli, VM ; Craig, TJ ; Dolovich, M ; Drazen, JM ; Fagan, JK ; Fahy, JV ; Fish, JE ; Ford, JG ; Israel, E ; Kiley, J ; Kraft, M ; Lazarus, SC ; Lemanske, RF ; Mauger, E ; Peters, SP ; Sorkness, CA

关键词: asthma;    beclomethasone dipropionate;    exhaled nitric oxide;    fluticasone propionate;    inhaled corticosteroid;    methacholine response;    pulmonary response;   

DOI  :  10.1067/mai.2002.122635

来源: Elsevier

【 摘 要 】

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 mug/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 mug/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 mug/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%) responses 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.

【 授权许可】

Free