Impact of Age and Administration Regimens on the Suppressive Effect of Inhaled Glucocorticoids on Eosinophil Markers in Children with Asthma

Abstract

Inhaled glucocorticoids may suppress the eosinophil markers serum eosinophil cationic protein (ECP) and urine eosinophil protein X (EPX) in children with asthma. The aim of the present study was to see whether age or administration regimen may affect the suppressive effect of inhaled budesonide on serum ECP or serum or urine EPX in children with asthma. Two separate randomized double-blind crossover trials with two treatment periods of 4 weeks duration were conducted. Study 1: Inhaled budesonide 400 mg twice daily versus placebo in 14 13-to 16-year-old adolescents. Study 2: Inhaled budesonide 800 mg once daily versus 400 mg twice daily in 22 prepubertal children aged 5-12 years. Blood and urine samples were collected on the last day of each period for assessment of serum ECP, serum EPX, and urine EPX by radioimmunoassays. In study 1 (the adolescent group), placebo and budesonide serum ECP (mean SEM) were 8.7 (0.9) and 5.5 (0.8) mg/L (p , 0.01), serum EPX 32.2 (2.9) and 24.7 (2.4 mg/L (p 5 0.04), and urine EPX/creatinine 41.6 (6.9) and 27.0 (2.8) mg/mmol (p 5 0.03), respectively). In study 2 (the prepubertal group), run in serum EPX (31.3 (2.8) mg/L) was reduced during both the budesonide 800 mg once daily [27.6 (2.6) mg/L (p 5 0.02)] and the 400 mg twice daily [25.0 (1.8) mg/L (p 5 0.01)] budesonide period, whereas serum ECP and urine EPX did not vary between the periods. Serum ECP and urine EPX may be more sensitive markers of anti-inflammatory effects of inhaled glucocorticoids in adolescents than in prepubertal children with asthma, and the suppressive effect seems not to differ between once-and twice-daily administration. (Pediatr Asthma Allergy Immunol 2004;17[1]:45-51.)

Eosinophil granule proteins in the assessment of airway inflammation in pediatric bronchial asthma

“…So far, one‐time blood and spot urine collections have been mainly used in clinical studies of ECP and EPX in children. Few of the studies gave information on the time of day at which sampling was performed (42–45) and many of them may have been influenced by marked circadian variations in the measures. We have recently reported serum ECP and EPX concentrations to be considerably higher during the night than during daytime with peak levels of ECP and EPX at 06.00 hours (both markers) and trough levels at 08.00 and 12.00 hours, respectively (46).…”

“…Again, conflicting results have been presented in children (15, 25, 29, 35, 42–44, 79, 81, 82). Serum ECP was suppressed in children treated with inhaled budesonide 400–600 µg (81, 82), serum ECP, serum EPX and urine EPX in children treated with 400–800 µg daily (15, 35, 45). Others have reported that serum ECP (42, 43), and serum and urine EPX (42) levels were not affected in children during treatment with inhaled fluticasone propionate 200 µg (42) or budesonide 400–800 µg per day (43) in spite of increased pulmonary function and decreased bronchial hyperreactivity.…”

“…In some of the studies the dose of the inhaled treatment varied during the observation period (79, 82). Few of the studies used randomized, double‐blind designs (42, 44, 45). Most of the studies, furthermore, were flawed by the lack of measures of compliance (15, 29, 35, 42, 43, 79, 81, 82).…”

Blood eosinophils as a marker of likely corticosteroid response in children with preschool wheeze: time for an eosinophil guided clinical trial?

“…The blood ECP concentration fell after initiation of ICS treatment and the authors suggested that ECP may be a useful marker of adherence to corticosteroid treatment [125]. However, a study by Wolthers et al [126] showed that blood ECP is not sensitive to ICS dose changes and in a study involving adults with chronic persistent asthma ICS caused a significant reduction in sputum and blood eosinophils but not sputum or blood ECP [127]. Review of the evidence suggests that sputum and blood ECP concentrations are not a sensitive or reliable means of evaluating airway inflammation.…”

Saliva and Serum Eosinophil Cationic Protein in Asthmatic Children and Adolescents with and without Allergic Sensitization

“…Blood-taking was performed between 11 am to 4 pm, which is when circadian rhythm of serum ECP is fairly stable (11). Three mL of venous blood was drawn via venipuncture, collected into Serum Separating Tubes (BD Diagnostics, Belliver Industrial Estate, Plymouth, PL6 78P, UK), and allowed to clot overnight at 4 • C. They were subsequently centrifuged at 3000g at room temperature for 5 minutes.…”