Eosinophil markers in blood, serum, and urine for monitoring the clinical course in childhood asthma: impact of budesonide treatment and withdrawal.
BACKGROUND
Markers of airway inflammation are needed for prediction of asthma deterioration and evaluation of disease severity. Few studies have focused on the dynamics of airway inflammation as reflected by the activity of the eosinophils and their proteins after withdrawal of inhaled corticosteroids.


OBJECTIVE
Our goal was to investigate the effect of withdrawal of inhaled budesonide on eosinophil count in blood and eosinophil proteins in serum and urine and to relate the levels of these markers to the risk of symptoms of asthma, increased bronchial hyperresponsiveness, and deterioration of lung function.


METHODS
Thirty-three children were randomly selected to continue or discontinue use of inhaled budesonide in a double-blind, placebo-controlled study. They were followed up for 4 months with regular analysis of blood, serum, and urine samples; lung function; and methacholine challenges. Eosinophil activity markers were analyzed. Age-matched healthy children provided reference data for all parameters measured.


RESULTS
The eosinophil number in blood and eosinophil protein levels in serum (serum eosinophil cationic protein [ECP] and serum eosinophil peroxidase [EPO]) increased significantly in the withdrawal group, and the difference between the groups was significant (P =.02 for all). Twenty-nine percent of the children in the withdrawal group remained symptom free. This subgroup had eosinophil counts at baseline below 350/microL, a serum ECP level below 15 microg/L, and a serum EPO level below 25 microg/L, each of which was related to a low risk of exacerbation (relative risk = 0.37, 0.48, and 0.37 respectively; P <.05 for all). All eosinophil markers were lower in the healthy children than in the symptom-free children with asthma.


CONCLUSIONS
Our data indicate that eosinophil count and/or ECP and EPO levels can be used to estimate the short-term risk of deterioration and the need for corticosteroid treatment in cases of mild and moderate allergic asthma.
Lönnkvist
K
K
Astrid Lindgren Children's Hospital, Stockholm; and the Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska Hospital, Stockholm.
Hellman
C
C
Lundahl
J
J
Halldén
G
G
Hedlin
G
G
D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001798:Blood Proteins / Q000032:analysis; D016535:Bronchial Hyperreactivity / Q000209:etiology; D001985:Bronchial Provocation Tests; D019819:Budesonide / Q000627:therapeutic use*; D002648:Child; D018450:Disease Progression; D004311:Double-Blind Method; D047091:Eosinophil Granule Proteins; D047209:Eosinophil Peroxidase; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D007958:Leukocyte Count; D008297:Male; D008562:Membrane Glycoproteins; D016210:Methacholine Chloride; D009195:Peroxidase / Q000097:blood; D010544:Peroxidases / Q000097:blood; D012260:Ribonucleases / Q000097:blood / Q000652:urine; D012882:Skin Tests; D013147:Spirometry; D060245:Tetraspanin 29
D018927:Anti-Asthmatic Agents; D015703:Antigens, CD; D015415:Biomarkers; D001798:Blood Proteins; C554869:CD9 protein, human; D047091:Eosinophil Granule Proteins; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D016210:Methacholine Chloride; D019819:Budesonide; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D009195:Peroxidase; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases