Quadrupling Inhaled Gluococorticoid Dose To Abort Asthma Exacerbations

Tricia McKeever, Kevin Mortimer, Andrew Wilson, Samantha Walker, Christopher Brightling, Andrew Skeggs, Ian D. Pavord, David B. Price, Lelia Duley, Mike Thomas, Lucy Bradshaw, Bernard Higgins, Rebecca Haydock, Eleanor J Mitchell, Graham Devereux, Timothy Harrison

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Abstract

BACKGROUND
Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.

METHODS
We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.

RESULTS
A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.

CONCLUSIONS
In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965.)
Original languageEnglish
Pages (from-to)902-910
Number of pages9
JournalThe New England Journal of Medicine
Volume378
Issue number10
Early online date3 Mar 2018
DOIs
Publication statusPublished - 8 Mar 2018

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Asthma
Glucocorticoids
Self Care
Random Allocation
Biomedical Technology Assessment
National Institutes of Health (U.S.)
Referral and Consultation
Confidence Intervals
Delivery of Health Care
Incidence
Therapeutics
Research

Cite this

McKeever, T., Mortimer, K., Wilson, A., Walker, S., Brightling, C., Skeggs, A., ... Harrison, T. (2018). Quadrupling Inhaled Gluococorticoid Dose To Abort Asthma Exacerbations. The New England Journal of Medicine, 378(10), 902-910. https://doi.org/10.1056/NEJMoa1714257

Quadrupling Inhaled Gluococorticoid Dose To Abort Asthma Exacerbations. / McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian D.; Price, David B.; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor J; Devereux, Graham; Harrison, Timothy.

In: The New England Journal of Medicine, Vol. 378, No. 10, 08.03.2018, p. 902-910.

Research output: Contribution to journalArticle

McKeever, T, Mortimer, K, Wilson, A, Walker, S, Brightling, C, Skeggs, A, Pavord, ID, Price, DB, Duley, L, Thomas, M, Bradshaw, L, Higgins, B, Haydock, R, Mitchell, EJ, Devereux, G & Harrison, T 2018, 'Quadrupling Inhaled Gluococorticoid Dose To Abort Asthma Exacerbations', The New England Journal of Medicine, vol. 378, no. 10, pp. 902-910. https://doi.org/10.1056/NEJMoa1714257
McKeever T, Mortimer K, Wilson A, Walker S, Brightling C, Skeggs A et al. Quadrupling Inhaled Gluococorticoid Dose To Abort Asthma Exacerbations. The New England Journal of Medicine. 2018 Mar 8;378(10):902-910. https://doi.org/10.1056/NEJMoa1714257
McKeever, Tricia ; Mortimer, Kevin ; Wilson, Andrew ; Walker, Samantha ; Brightling, Christopher ; Skeggs, Andrew ; Pavord, Ian D. ; Price, David B. ; Duley, Lelia ; Thomas, Mike ; Bradshaw, Lucy ; Higgins, Bernard ; Haydock, Rebecca ; Mitchell, Eleanor J ; Devereux, Graham ; Harrison, Timothy. / Quadrupling Inhaled Gluococorticoid Dose To Abort Asthma Exacerbations. In: The New England Journal of Medicine. 2018 ; Vol. 378, No. 10. pp. 902-910.
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abstract = "BACKGROUNDAsthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.METHODSWe conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.RESULTSA total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45{\%}) in the quadrupling group as compared with 484 (52{\%}) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95{\%} confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.CONCLUSIONSIn this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965.)",
author = "Tricia McKeever and Kevin Mortimer and Andrew Wilson and Samantha Walker and Christopher Brightling and Andrew Skeggs and Pavord, {Ian D.} and Price, {David B.} and Lelia Duley and Mike Thomas and Lucy Bradshaw and Bernard Higgins and Rebecca Haydock and Mitchell, {Eleanor J} and Graham Devereux and Timothy Harrison",
note = "Supported by the Health Technology Assessment Programme of the National Institute for Health Research. We thank the trial participants, all the staff at the trial sites and the Nottingham Clinical Trial Unit who managed the trial, the members of the independent trial steering committee (Philip Ind [chair], consultant respiratory physician, Imperial College Healthcare NHS Trust; Adel Mansur, consultant physician, Birmingham Heartlands Hospital; Jacqui Cooper, chronic obstructive pulmonary disease–respiratory team leader, Keyworth Primary Care Centre; and Kim-Leng Hills, patient representative), and the members of the independent data monitoring committee (Steven Julious [chair], professor of medical statistics, University of Sheffield; Ian Sabroe, professor of inflammation biology, University of Sheffield; and Stephen Scott, consultant respiratory physician, Countess of Chester Hospital).",
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AU - McKeever, Tricia

AU - Mortimer, Kevin

AU - Wilson, Andrew

AU - Walker, Samantha

AU - Brightling, Christopher

AU - Skeggs, Andrew

AU - Pavord, Ian D.

AU - Price, David B.

AU - Duley, Lelia

AU - Thomas, Mike

AU - Bradshaw, Lucy

AU - Higgins, Bernard

AU - Haydock, Rebecca

AU - Mitchell, Eleanor J

AU - Devereux, Graham

AU - Harrison, Timothy

N1 - Supported by the Health Technology Assessment Programme of the National Institute for Health Research. We thank the trial participants, all the staff at the trial sites and the Nottingham Clinical Trial Unit who managed the trial, the members of the independent trial steering committee (Philip Ind [chair], consultant respiratory physician, Imperial College Healthcare NHS Trust; Adel Mansur, consultant physician, Birmingham Heartlands Hospital; Jacqui Cooper, chronic obstructive pulmonary disease–respiratory team leader, Keyworth Primary Care Centre; and Kim-Leng Hills, patient representative), and the members of the independent data monitoring committee (Steven Julious [chair], professor of medical statistics, University of Sheffield; Ian Sabroe, professor of inflammation biology, University of Sheffield; and Stephen Scott, consultant respiratory physician, Countess of Chester Hospital).

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N2 - BACKGROUNDAsthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.METHODSWe conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.RESULTSA total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.CONCLUSIONSIn this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965.)

AB - BACKGROUNDAsthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma.METHODSWe conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma.RESULTSA total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group.CONCLUSIONSIn this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965.)

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