Clinical and immunologic factors associated with the presence or absence of airways hyper-responsiveness in childhood asthma

M J Visser, P L P Brand, H M Boezen, W M C van Aalderen, H F Kauffman, D S Postma

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Abstract

BACKGROUND: During the baseline period of a clinical trial comparing different dosage schedules of inhaled steroids, asthmatic children (aged 6-10 years) were expected to meet the inclusion criterion of airways hyper-responsiveness (PD(20) methacholine < 80 micro g) after withdrawal of inhaled corticosteroids for 2-8 weeks. However, many children failed to do so.

OBJECTIVE: It has been shown that young wheezing children may outgrow their symptoms. We investigated if differences between children with and without airways hyper-responsiveness after withdrawal of inhaled corticosteroids were compatible with differences between transient and persistent wheezers found in other studies.

METHODS: Seventy-eight children entered the study, of which 41 developed airways hyper- responsiveness after withdrawal of inhaled corticosteroids, and 37 did not. These two groups of children were compared with respect to differences in demographic, clinical, and immunological features (IL-4, IL-5, IL-10, and IFN-gamma produced by Con A stimulated peripheral mononuclear cells (PBMCs) and serum IL-4, IL-5 and soluble intercellular adhesion molecule-1 (sICAM-1)).

RESULTS: Hyper-responsive children had more atopic features (positive RAST, high IgE, eczema), lower levels of FEV1 and lower concentrations of sICAM-1 than non-hyper-responsive children. Apart from a borderline significantly higher IL-4 production in the hyper-responsive group, other immunologic parameters were comparable. Multivariate logistic regression analysis showed that high serum IgE, low FEV1, and low sICAM-1 levels were independently associated with the presence of airways hyper-responsiveness after stopping inhaled corticosteroids. Atopy was associated with higher concentrations of IL-4 in the hyper-responsive group.

CONCLUSION: After withdrawal of inhaled corticosteroids many children previously diagnosed with asthma did not develop airways hyper-responsiveness. We conclude that hyper-responsive children share features with persistent wheezers as found in previous studies, whereas the non-hyper- responsive children may represent transient wheezers.

Original languageEnglish
Pages (from-to)1278-1284
Number of pages7
JournalClinical and Experimental Allergy
Volume32
Issue number9
Publication statusPublished - Sep-2002

Keywords

  • child
  • asthma
  • wheeze
  • airways hyper-responsiveness
  • inhaled corticosteroids
  • cytokines
  • inflammation
  • INTERCELLULAR-ADHESION MOLECULE-1
  • LONG-TERM TREATMENT
  • INHALED CORTICOSTEROID BUDESONIDE
  • INTERFERON-GAMMA
  • BRONCHIAL RESPONSIVENESS
  • LUNG-FUNCTION
  • CHILDREN
  • ATOPY
  • HYPERRESPONSIVENESS
  • INTERLEUKIN-4

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