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 FEV 1 and PC 20; 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 FEV 1 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 PC 20 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%) FEV 1 response, in contrast to poor (1/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC 20, in contrast to poor (1 and PC 20 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
JournalThe Journal of Allergy and Clinical Immunology
Volume109
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Metered Dose Inhalers
Adrenal Cortex Hormones
Asthma
Beclomethasone
Dry Powder Inhalers
Hydrocortisone
Chlorofluorocarbons
Therapeutics
Methacholine Chloride
Vital Capacity
Multicenter Studies
Fluticasone
Odds Ratio

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Szefler, S. J., Martin, R. J., King, T. S., Boushey, H. A., Cherniack, R. M., Chinchilli, V. M., ... Sorkness, C. A. (2002). Significant variability in response to inhaled corticosteroids for persistent asthma. The Journal of Allergy and Clinical Immunology, 109(3), 410-418. https://doi.org/10.1067/mai.2002.122635

Significant variability in response to inhaled corticosteroids for persistent asthma. / Szefler, Stanley J.; Martin, Richard J.; King, Tonya Sharp; Boushey, Homer A.; Cherniack, Reuben M.; Chinchilli, Vernon M.; Craig, Timothy J.; Dolovich, Myrna; Drazen, Jeffrey M.; Fagan, Joanne K.; Fahy, John V.; Fish, James E.; Ford, Jean G.; Israel, Elliot; Kiley, James; Kraft, Monica; Lazarus, Stephen C.; Lemanske, Robert F.; Mauger, Elizabeth; Peters, Stephen P.; Sorkness, Christine A.

In: The Journal of Allergy and Clinical Immunology, Vol. 109, No. 3, 2002, p. 410-418.

Research output: Contribution to journalArticle

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 2002, 'Significant variability in response to inhaled corticosteroids for persistent asthma', The Journal of Allergy and Clinical Immunology, vol. 109, no. 3, pp. 410-418. https://doi.org/10.1067/mai.2002.122635
Szefler, Stanley J. ; Martin, Richard J. ; King, Tonya Sharp ; Boushey, Homer A. ; Cherniack, Reuben M. ; Chinchilli, Vernon M. ; Craig, Timothy J. ; Dolovich, Myrna ; Drazen, Jeffrey M. ; Fagan, Joanne K. ; Fahy, John V. ; Fish, James E. ; Ford, Jean G. ; Israel, Elliot ; Kiley, James ; Kraft, Monica ; Lazarus, Stephen C. ; Lemanske, Robert F. ; Mauger, Elizabeth ; Peters, Stephen P. ; Sorkness, Christine A. / Significant variability in response to inhaled corticosteroids for persistent asthma. In: The Journal of Allergy and Clinical Immunology. 2002 ; Vol. 109, No. 3. pp. 410-418.
@article{cf470c10bed24f868e814077a6916bfe,
title = "Significant variability in response to inhaled corticosteroids for persistent asthma",
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 FEV 1 and PC 20; 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 FEV 1 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 PC 20 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{\%}) FEV 1 response, in contrast to poor (1/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC 20, in contrast to poor (1 and PC 20 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.",
keywords = "Asthma, Beclomethasone dipropionate, Exhaled nitric oxide, Fluticasone propionate, Inhaled corticosteroid, Methacholine response, Pulmonary response",
author = "Szefler, {Stanley J.} and Martin, {Richard J.} and King, {Tonya Sharp} and Boushey, {Homer A.} and Cherniack, {Reuben M.} and Chinchilli, {Vernon M.} and Craig, {Timothy J.} and Myrna Dolovich and Drazen, {Jeffrey M.} and Fagan, {Joanne K.} and Fahy, {John V.} and Fish, {James E.} and Ford, {Jean G.} and Elliot Israel and James Kiley and Monica Kraft and Lazarus, {Stephen C.} and Lemanske, {Robert F.} and Elizabeth Mauger and Peters, {Stephen P.} and Sorkness, {Christine A.}",
year = "2002",
doi = "10.1067/mai.2002.122635",
language = "English (US)",
volume = "109",
pages = "410--418",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Significant variability in response to inhaled corticosteroids for persistent asthma

AU - Szefler, Stanley J.

AU - Martin, Richard J.

AU - King, Tonya Sharp

AU - Boushey, Homer A.

AU - Cherniack, Reuben M.

AU - Chinchilli, Vernon M.

AU - Craig, Timothy J.

AU - Dolovich, Myrna

AU - Drazen, Jeffrey M.

AU - Fagan, Joanne K.

AU - Fahy, John V.

AU - Fish, James E.

AU - Ford, Jean G.

AU - Israel, Elliot

AU - Kiley, James

AU - Kraft, Monica

AU - Lazarus, Stephen C.

AU - Lemanske, Robert F.

AU - Mauger, Elizabeth

AU - Peters, Stephen P.

AU - Sorkness, Christine A.

PY - 2002

Y1 - 2002

N2 - 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 FEV 1 and PC 20; 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 FEV 1 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 PC 20 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%) FEV 1 response, in contrast to poor (1/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC 20, in contrast to poor (1 and PC 20 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.

AB - 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 FEV 1 and PC 20; 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 FEV 1 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 PC 20 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%) FEV 1 response, in contrast to poor (1/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC 20, in contrast to poor (1 and PC 20 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.

KW - Asthma

KW - Beclomethasone dipropionate

KW - Exhaled nitric oxide

KW - Fluticasone propionate

KW - Inhaled corticosteroid

KW - Methacholine response

KW - Pulmonary response

UR - http://www.scopus.com/inward/record.url?scp=0036126690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036126690&partnerID=8YFLogxK

U2 - 10.1067/mai.2002.122635

DO - 10.1067/mai.2002.122635

M3 - Article

C2 - 11897984

AN - SCOPUS:0036126690

VL - 109

SP - 410

EP - 418

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -