Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma

Nathan Rabinovitch, David T. Mauger, Nichole Reisdorph, Ronina Covar, Jonathan Malka, Robert F. Lemanske, Wayne J Morgan, Theresa W. Guilbert, Robert S. Zeiger, Leonard B. Bacharier, Stanley J. Szefler

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background Predictors of improvement in asthma control and lung function to step 3 therapy in children with persistent asthma have not been identified despite reported heterogeneity in responsiveness. Objective We sought to evaluate potential predictors of asthma control and lung function responsiveness to step 3 therapy. Methods A post hoc analysis from the Best Add-On Giving Effective Response (BADGER) study tested the association between baseline biological, asthma control, pulmonary function, and demographic markers and responsiveness to step-up to a higher dose of inhaled corticosteroid (ICS step-up therapy) or addition of leukotriene receptor antagonist (LTRA step-up therapy) or long-acting β2-agonist (LABA step-up therapy). Results In multivariate analyses higher impulse oscillometry reactance area was associated (P =.048) with a differential FEV1 response favoring LABA over ICS step-up therapy, whereas higher urinary leukotriene E4 levels were marginally (P =.053) related to a differential FEV1 response favoring LTRA over LABA step-up therapy. Predictors of differential responses comparing ICS with LTRA step-up therapy were not apparent, probably because of suppression of allergic markers with low-dose ICS treatment. Minimal overlap was seen across FEV1 and asthma control day predictors, suggesting distinct mechanisms related to lung function and asthma control day responses. Conclusion Levels of impulse oscillometry reactance area indicating peripheral airway obstruction and urinary leukotriene E4 levels indicating cysteinyl leukotriene inflammation can differentiate LABA step-up responses from responses to LTRA or ICS step-up therapy. Further studies with physiologic, genetic, and biological markers related to these phenotypes will be needed to predict individual responses to LABA step-up therapy.

Original languageEnglish (US)
Pages (from-to)350-356
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number2
DOIs
StatePublished - Feb 2014

Fingerprint

Asthma
Lung
Oscillometry
Therapeutics
Leukotriene E4
Leukotriene Antagonists
Airway Obstruction
Genetic Markers
Adrenal Cortex Hormones
Multivariate Analysis
Biomarkers
Demography
Inflammation
Phenotype

Keywords

  • Asthma
  • Best Add-On Giving Effective Response
  • children
  • fraction of exhaled nitric oxide
  • impulse oscillometry
  • inhaled corticosteroids
  • leukotriene E
  • leukotriene receptor antagonist
  • long-acting β-agonist

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rabinovitch, N., Mauger, D. T., Reisdorph, N., Covar, R., Malka, J., Lemanske, R. F., ... Szefler, S. J. (2014). Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma. Journal of Allergy and Clinical Immunology, 133(2), 350-356. https://doi.org/10.1016/j.jaci.2013.07.039

Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma. / Rabinovitch, Nathan; Mauger, David T.; Reisdorph, Nichole; Covar, Ronina; Malka, Jonathan; Lemanske, Robert F.; Morgan, Wayne J; Guilbert, Theresa W.; Zeiger, Robert S.; Bacharier, Leonard B.; Szefler, Stanley J.

In: Journal of Allergy and Clinical Immunology, Vol. 133, No. 2, 02.2014, p. 350-356.

Research output: Contribution to journalArticle

Rabinovitch, N, Mauger, DT, Reisdorph, N, Covar, R, Malka, J, Lemanske, RF, Morgan, WJ, Guilbert, TW, Zeiger, RS, Bacharier, LB & Szefler, SJ 2014, 'Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma', Journal of Allergy and Clinical Immunology, vol. 133, no. 2, pp. 350-356. https://doi.org/10.1016/j.jaci.2013.07.039
Rabinovitch, Nathan ; Mauger, David T. ; Reisdorph, Nichole ; Covar, Ronina ; Malka, Jonathan ; Lemanske, Robert F. ; Morgan, Wayne J ; Guilbert, Theresa W. ; Zeiger, Robert S. ; Bacharier, Leonard B. ; Szefler, Stanley J. / Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma. In: Journal of Allergy and Clinical Immunology. 2014 ; Vol. 133, No. 2. pp. 350-356.
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abstract = "Background Predictors of improvement in asthma control and lung function to step 3 therapy in children with persistent asthma have not been identified despite reported heterogeneity in responsiveness. Objective We sought to evaluate potential predictors of asthma control and lung function responsiveness to step 3 therapy. Methods A post hoc analysis from the Best Add-On Giving Effective Response (BADGER) study tested the association between baseline biological, asthma control, pulmonary function, and demographic markers and responsiveness to step-up to a higher dose of inhaled corticosteroid (ICS step-up therapy) or addition of leukotriene receptor antagonist (LTRA step-up therapy) or long-acting β2-agonist (LABA step-up therapy). Results In multivariate analyses higher impulse oscillometry reactance area was associated (P =.048) with a differential FEV1 response favoring LABA over ICS step-up therapy, whereas higher urinary leukotriene E4 levels were marginally (P =.053) related to a differential FEV1 response favoring LTRA over LABA step-up therapy. Predictors of differential responses comparing ICS with LTRA step-up therapy were not apparent, probably because of suppression of allergic markers with low-dose ICS treatment. Minimal overlap was seen across FEV1 and asthma control day predictors, suggesting distinct mechanisms related to lung function and asthma control day responses. Conclusion Levels of impulse oscillometry reactance area indicating peripheral airway obstruction and urinary leukotriene E4 levels indicating cysteinyl leukotriene inflammation can differentiate LABA step-up responses from responses to LTRA or ICS step-up therapy. Further studies with physiologic, genetic, and biological markers related to these phenotypes will be needed to predict individual responses to LABA step-up therapy.",
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AU - Morgan, Wayne J

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N2 - Background Predictors of improvement in asthma control and lung function to step 3 therapy in children with persistent asthma have not been identified despite reported heterogeneity in responsiveness. Objective We sought to evaluate potential predictors of asthma control and lung function responsiveness to step 3 therapy. Methods A post hoc analysis from the Best Add-On Giving Effective Response (BADGER) study tested the association between baseline biological, asthma control, pulmonary function, and demographic markers and responsiveness to step-up to a higher dose of inhaled corticosteroid (ICS step-up therapy) or addition of leukotriene receptor antagonist (LTRA step-up therapy) or long-acting β2-agonist (LABA step-up therapy). Results In multivariate analyses higher impulse oscillometry reactance area was associated (P =.048) with a differential FEV1 response favoring LABA over ICS step-up therapy, whereas higher urinary leukotriene E4 levels were marginally (P =.053) related to a differential FEV1 response favoring LTRA over LABA step-up therapy. Predictors of differential responses comparing ICS with LTRA step-up therapy were not apparent, probably because of suppression of allergic markers with low-dose ICS treatment. Minimal overlap was seen across FEV1 and asthma control day predictors, suggesting distinct mechanisms related to lung function and asthma control day responses. Conclusion Levels of impulse oscillometry reactance area indicating peripheral airway obstruction and urinary leukotriene E4 levels indicating cysteinyl leukotriene inflammation can differentiate LABA step-up responses from responses to LTRA or ICS step-up therapy. Further studies with physiologic, genetic, and biological markers related to these phenotypes will be needed to predict individual responses to LABA step-up therapy.

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