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


CONCLUSIONS
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.
Visser
M J
MJ
Department of Pulmonology, University Hospital Groningen, The Netherlands.
Brand
P L P
PL
Boezen
H M
HM
van Aalderen
W M C
WM
Kauffman
H F
HF
Postma
D S
DS
D000818:Animals; D000829:Animals, Domestic; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D001724:Birth Weight; D001942:Breast Feeding; D001944:Breath Tests; D016535:Bronchial Hyperreactivity; D016085:Bronchoconstrictor Agents; D015815:Cell Adhesion Molecules / Q000097:blood; D002648:Child; D003208:Concanavalin A; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016015:Logistic Models; D008213:Lymphocyte Activation; D008297:Male; D016210:Methacholine Chloride; D009569:Nitric Oxide / Q000032:analysis; D012129:Respiratory Function Tests; D012907:Smoking; D019564:Unnecessary Procedures
D016085:Bronchoconstrictor Agents; D015815:Cell Adhesion Molecules; D005938:Glucocorticoids; D015848:Interleukin-5; D016210:Methacholine Chloride; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma