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Predictors of poor response during asthma therapy differ with definition of outcome

Angela J Rogers1, Kelan G Tantisira, Anne L Fuhlbrigge

  • 1Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. reajr@channing.harvard.edu

Pharmacogenomics
|August 12, 2009
PubMed

Insights

Predictors of poor response to inhaled corticosteroids in children with asthma vary. Clinical factors like prior exacerbations predict symptom recurrence, while genetic factors and lung function predict lung response.

Area of Science:

  • Pediatric Pulmonology
  • Pharmacogenetics
  • Asthma Management

Background:

  • Long-term response to inhaled corticosteroids (ICS) in pediatric asthma is variable.
  • Identifying predictors of poor ICS response is crucial for personalized treatment strategies.

Purpose of the Study:

  • To identify phenotypic and genetic factors associated with poor long-term response to ICS in children with asthma.
  • To differentiate predictors based on response outcomes: lung function versus asthma exacerbations.

Main Methods:

  • A cohort of 311 children (5-12 years) from the Childhood Asthma Management Program (CAMP) was analyzed.
  • Phenotypic variables (e.g., age, IgE, bronchodilator response) and genetic polymorphisms (FCER2, CRHR1) were assessed.
  • Participants received a 4-year course of ICS.

Main Results:

  • Predictors for asthma exacerbations (prior exacerbations, younger age, higher IgE) differ from those for lung function response (lower bronchodilator response, specific CRHR1 and FCER2 alleles).
  • Poor lung function response did not increase exacerbation risk, and vice versa.
  • RS242941 in CRHR1 and T2206C in FCER2 minor alleles were linked to poor lung function response.

Conclusions:

  • Phenotypic and genetic predictors of poor ICS response in asthma are outcome-dependent (exacerbations vs. lung function).
  • These distinct predictors have implications for comparing clinical trial outcomes.
  • Findings guide the design of future pharmacogenetic studies in pediatric asthma.
Abstract

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