Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations

D. J. Jackson, L. B. Bacharier, D. T. Mauger, S. Boehmer, A. Beigelman, J. F. Chmiel, A. M. Fitzpatrick, J. M. Gaffin, W. J. Morgan, S. P. Peters, W. Phipatanakul, W. J. Sheehan, M. D. Cabana, F. Holguin, F. D. Martinez, J. A. Pongracic, S. N. Baxi, M. Benson, K. Blake, R. CovarD. A. Gentile, E. Israel, J. A. Krishnan, H. V. Kumar, J. E. Lang, S. C. Lazarus, J. J. Lima, D. Long, N. Ly, J. Marbin, J. N. Moy, R. E. Myers, J. T. Olin, H. H. Raissy, R. G. Robison, K. Ross, C. A. Sorkness, R. F. Lemanske

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (highdose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the highdose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P = 0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellowzone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P = 0.06). CONCLUSIONS In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129.)

Original languageEnglish (US)
Pages (from-to)891-901
Number of pages11
JournalNew England Journal of Medicine
Volume378
Issue number10
DOIs
StatePublished - Mar 8 2018
Externally publishedYes

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Glucocorticoids
Asthma
Inhalation
National Heart, Lung, and Blood Institute (U.S.)
Albuterol
Growth
Treatment Failure
Maintenance
Confidence Intervals
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jackson, D. J., Bacharier, L. B., Mauger, D. T., Boehmer, S., Beigelman, A., Chmiel, J. F., ... Lemanske, R. F. (2018). Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. New England Journal of Medicine, 378(10), 891-901. https://doi.org/10.1056/NEJMoa1710988

Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. / Jackson, D. J.; Bacharier, L. B.; Mauger, D. T.; Boehmer, S.; Beigelman, A.; Chmiel, J. F.; Fitzpatrick, A. M.; Gaffin, J. M.; Morgan, W. J.; Peters, S. P.; Phipatanakul, W.; Sheehan, W. J.; Cabana, M. D.; Holguin, F.; Martinez, F. D.; Pongracic, J. A.; Baxi, S. N.; Benson, M.; Blake, K.; Covar, R.; Gentile, D. A.; Israel, E.; Krishnan, J. A.; Kumar, H. V.; Lang, J. E.; Lazarus, S. C.; Lima, J. J.; Long, D.; Ly, N.; Marbin, J.; Moy, J. N.; Myers, R. E.; Olin, J. T.; Raissy, H. H.; Robison, R. G.; Ross, K.; Sorkness, C. A.; Lemanske, R. F.

In: New England Journal of Medicine, Vol. 378, No. 10, 08.03.2018, p. 891-901.

Research output: Contribution to journalArticle

Jackson, DJ, Bacharier, LB, Mauger, DT, Boehmer, S, Beigelman, A, Chmiel, JF, Fitzpatrick, AM, Gaffin, JM, Morgan, WJ, Peters, SP, Phipatanakul, W, Sheehan, WJ, Cabana, MD, Holguin, F, Martinez, FD, Pongracic, JA, Baxi, SN, Benson, M, Blake, K, Covar, R, Gentile, DA, Israel, E, Krishnan, JA, Kumar, HV, Lang, JE, Lazarus, SC, Lima, JJ, Long, D, Ly, N, Marbin, J, Moy, JN, Myers, RE, Olin, JT, Raissy, HH, Robison, RG, Ross, K, Sorkness, CA & Lemanske, RF 2018, 'Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations', New England Journal of Medicine, vol. 378, no. 10, pp. 891-901. https://doi.org/10.1056/NEJMoa1710988
Jackson DJ, Bacharier LB, Mauger DT, Boehmer S, Beigelman A, Chmiel JF et al. Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. New England Journal of Medicine. 2018 Mar 8;378(10):891-901. https://doi.org/10.1056/NEJMoa1710988
Jackson, D. J. ; Bacharier, L. B. ; Mauger, D. T. ; Boehmer, S. ; Beigelman, A. ; Chmiel, J. F. ; Fitzpatrick, A. M. ; Gaffin, J. M. ; Morgan, W. J. ; Peters, S. P. ; Phipatanakul, W. ; Sheehan, W. J. ; Cabana, M. D. ; Holguin, F. ; Martinez, F. D. ; Pongracic, J. A. ; Baxi, S. N. ; Benson, M. ; Blake, K. ; Covar, R. ; Gentile, D. A. ; Israel, E. ; Krishnan, J. A. ; Kumar, H. V. ; Lang, J. E. ; Lazarus, S. C. ; Lima, J. J. ; Long, D. ; Ly, N. ; Marbin, J. ; Moy, J. N. ; Myers, R. E. ; Olin, J. T. ; Raissy, H. H. ; Robison, R. G. ; Ross, K. ; Sorkness, C. A. ; Lemanske, R. F. / Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. In: New England Journal of Medicine. 2018 ; Vol. 378, No. 10. pp. 891-901.
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abstract = "BACKGROUND Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (highdose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ({"}yellow zone{"}). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the highdose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95{\%} confidence interval, 0.8 to 2.1; P = 0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellowzone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16{\%} higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P = 0.06). CONCLUSIONS In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129.)",
author = "Jackson, {D. J.} and Bacharier, {L. B.} and Mauger, {D. T.} and S. Boehmer and A. Beigelman and Chmiel, {J. F.} and Fitzpatrick, {A. M.} and Gaffin, {J. M.} and Morgan, {W. J.} and Peters, {S. P.} and W. Phipatanakul and Sheehan, {W. J.} and Cabana, {M. D.} and F. Holguin and Martinez, {F. D.} and Pongracic, {J. A.} and Baxi, {S. N.} and M. Benson and K. Blake and R. Covar and Gentile, {D. A.} and E. Israel and Krishnan, {J. A.} and Kumar, {H. V.} and Lang, {J. E.} and Lazarus, {S. C.} and Lima, {J. J.} and D. Long and N. Ly and J. Marbin and Moy, {J. N.} and Myers, {R. E.} and Olin, {J. T.} and Raissy, {H. H.} and Robison, {R. G.} and K. Ross and Sorkness, {C. A.} and Lemanske, {R. F.}",
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TY - JOUR

T1 - Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations

AU - Jackson, D. J.

AU - Bacharier, L. B.

AU - Mauger, D. T.

AU - Boehmer, S.

AU - Beigelman, A.

AU - Chmiel, J. F.

AU - Fitzpatrick, A. M.

AU - Gaffin, J. M.

AU - Morgan, W. J.

AU - Peters, S. P.

AU - Phipatanakul, W.

AU - Sheehan, W. J.

AU - Cabana, M. D.

AU - Holguin, F.

AU - Martinez, F. D.

AU - Pongracic, J. A.

AU - Baxi, S. N.

AU - Benson, M.

AU - Blake, K.

AU - Covar, R.

AU - Gentile, D. A.

AU - Israel, E.

AU - Krishnan, J. A.

AU - Kumar, H. V.

AU - Lang, J. E.

AU - Lazarus, S. C.

AU - Lima, J. J.

AU - Long, D.

AU - Ly, N.

AU - Marbin, J.

AU - Moy, J. N.

AU - Myers, R. E.

AU - Olin, J. T.

AU - Raissy, H. H.

AU - Robison, R. G.

AU - Ross, K.

AU - Sorkness, C. A.

AU - Lemanske, R. F.

PY - 2018/3/8

Y1 - 2018/3/8

N2 - BACKGROUND Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (highdose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the highdose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P = 0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellowzone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P = 0.06). CONCLUSIONS In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129.)

AB - BACKGROUND Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (highdose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the highdose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P = 0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellowzone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P = 0.06). CONCLUSIONS In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129.)

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