Influence of different dosage schedules of inhaled fluticasone propionate on peripheral blood cytokine concentrations in childhood asthma.
BACKGROUND
Asthma is characterized by eosinophilic airways inflammation with elevated levels of IL-4, IL-5 and sICAM-1, and reduced levels of IL-10 and IFN-gamma. Inhaled corticosteroids powerfully reduce airways inflammation.


OBJECTIVE
To investigate if eosinophil counts, serum eosinophilic cationic protein (ECP) and sICAM-1 levels, as well as serum and production of cytokines (IL-4, IL-5, IL-10, IFN-gamma) by peripheral blood monocytes (PBMCs) are useful markers to monitor therapy with inhaled fluticasone propionate (FP) in asthmatic children.


METHODS
In a double-blind, 1-year study, 55 asthmatic children (aged 6-10 years) stopped inhaled corticosteroids for a mean period of 24 days and were randomized to receive either FP 200 microg/day (constant dose group), or a starting dose of FP 1000 microg/day with two monthly reductions to 500, 200 and 100 microg/day (stepdown group). Hyper-responsiveness, symptom scores and blood sampling were performed at 2-month intervals.


RESULTS
Symptoms and hyper-responsiveness improved significantly in both treatment groups after reintroduction of FP. Eosinophil counts decreased significantly more during the first 2 months of FP in the stepdown group than in the constant dose group (P = 0.03). We found a trend towards a dose-dependent response in changes of eosinophil counts and serum ECP levels during treatment. Serum IL-4 and IL-5 levels were undetectable in the majority of children. No significant effect of the dose of FP on the release of IL-4, IL-5, IL-10 or IFN-gamma by Con A stimulated PBMCs was found. sICAM-1 levels did not significantly differ at any time point between the two groups.


CONCLUSIONS
Serum ECP as well as peripheral blood eosinophils, cytokine production by PBMCs and sICAM-1 levels are insensitive markers in titrating and monitoring therapy with inhaled corticosteroids over a wide dose range in childhood asthma.
Visser
M J
MJ
Department of Pulmonology, University Hospital Groningen, the Netherlands.
Postma
D S
DS
Brand
P L P
PL
Arends
L R
LR
Duiverman
E J
EJ
Kauffman
H F
HF
D000280:Administration, Inhalation; D000287:Administration, Topical; D000730:Androstadienes / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis; D016535:Bronchial Hyperreactivity; D015815:Cell Adhesion Molecules / Q000097:blood; D002648:Child; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D047091:Eosinophil Granule Proteins; D004804:Eosinophils; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D012260:Ribonucleases
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D047091:Eosinophil Granule Proteins; D005938:Glucocorticoids; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D000068298:Fluticasone; D012260:Ribonucleases