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

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.

• Authors: Nathan Rabinovitch, David T Mauger, Nichole Reisdorph, Ronina Covar, Jonathan Malka, Robert F Lemanske Jr, Wayne J Morgan, Theresa W Guilbert, Robert S Zeiger, Leonard B Bacharier, Stanley J Szefler
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 133 Issue 2 Pg. 350-6 (Feb 2014) ISSN: 1097-6825 [Electronic] United States
• PMID: 24084071 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Acetates
• Adrenergic beta-Agonists
• Androstadienes
• Anti-Asthmatic Agents
• Biomarkers
• Bronchodilator Agents
• Cyclopropanes
• Leukotriene Antagonists
• Quinolines
• Sulfides
• Salmeterol Xinafoate
• Leukotriene E4
• Fluticasone
• montelukast
• Albuterol

Topics

• Acetates (administration & dosage)
• Adolescent
• Adrenergic beta-Agonists (administration & dosage)
• Albuterol (administration & dosage, analogs & derivatives)
• Androstadienes (administration & dosage)
• Anti-Asthmatic Agents (administration & dosage)
• Asthma (drug therapy, metabolism, physiopathology)
• Biomarkers (urine)
• Bronchodilator Agents (administration & dosage)
• Child
• Cross-Over Studies
• Cyclopropanes
• Eosinophils (cytology)
• Female
• Fluticasone
• Forced Expiratory Volume
• Humans
• Leukocyte Count
• Leukotriene Antagonists (administration & dosage)
• Leukotriene E4 (urine)
• Male
• Quinolines (administration & dosage)
• Salmeterol Xinafoate
• Sulfides
• Vital Capacity