Assessment of corticosteroid response in pediatric patients with severe asthma by using a multidomain approach

J Allergy Clin Immunol. 2016 Aug;138(2):413-420.e6. doi: 10.1016/j.jaci.2015.12.1347. Epub 2016 Apr 6.

Abstract

Background: There is no agreed upon definition of systemic corticosteroid response in asthmatic children. Moreover, pediatric severe therapy-resistant asthma (STRA) is heterogeneous, and thus response to steroids is unlikely to be uniform in all patients.

Objective: We sought to evaluate the utility of a multidomain approach incorporating symptoms, lung function, and inflammation to determine steroid responsiveness in pediatric patients with STRA.

Methods: Eighty-two children (median age, 12 years) with STRA received a clinically indicated dose of intramuscular steroid. Changes in 4 separate domains were assessed 4 weeks after intramuscular triamcinolone acetonide: normalization of (1) symptoms (Asthma Control Test score, >19/25 or 50% increase), (2) spirometric results (FEV1 ≥80% of predicted value or ≥15% increase), (3) fraction of exhaled nitric oxide levels (<24 ppb), and (4) sputum eosinophil counts (<2.5%). Fifty-four of 82 children had complete data in all 4 domains.

Results: Twenty-three (43%) of 54 children had a symptom response, 29 (54%) of 54 had a lung function response, 28 (52%) of 54 had a fraction of exhaled nitric oxide response, and 29 (54%) of 54 had a sputum eosinophil response. Although a similar proportion of children responded to systemic corticosteroids in each domain, there were no reliable predictors of a response pattern. Seven (13%) of 54 were complete responders (response in all domains), 8 (15%) of 54 were nonresponders (no response in any domain), and 39 (72%) of 54 were partial responders (response in ≥1 domain).

Conclusions: A multidomain evaluation of systemic steroid responsiveness using pragmatic clinical assessments confirms childhood STRA is heterogeneous and that a complete response in symptoms and inflammatory and physiologic parameters is rare. Individual response patterns to systemic steroids might be useful in guiding the choice of add-on therapies in each child as a step toward achieving personalized medicine.

Keywords: Pediatric; inflammation; severe asthma; spirometry; steroid response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / therapeutic use*
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / diagnosis*
  • Asthma / drug therapy*
  • Biomarkers
  • Child
  • Eosinophils / pathology
  • Female
  • Forced Expiratory Volume
  • Humans
  • Leukocyte Count
  • Male
  • Nitric Oxide / metabolism
  • Severity of Illness Index
  • Spirometry
  • Sputum / cytology
  • Treatment Outcome
  • Workflow

Substances

  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Biomarkers
  • Nitric Oxide