Prospective longitudinal study of urinary eosinophil protein X in children with asthma and chronic cough

Abstract

Airway inflammation is the principal abnormality in asthma and many other respiratory diseases. Eosinophils are the cells primarily involved in this process. The aim of this study was to analyze sequential changes in urinary eosinophil protein X (EPX) a biological marker of eosinophil activation in asthmatic children and chronic coughers, and to confirm the importance of such changes in evaluating the inflammatory process once regular treatment was initiated. Eighty-eight asthmatic children (AC), 33 children with chronic cough (CC), and 34 control children were included in the study. All those with respiratory disease underwent allergy tests (serum total IgE, serum-specific IgE for common allergens, peripheral blood eosinophil (PBE), and skin prick tests) and a pulmonary function test (PFT), and had chest X-ray and serum eosinophil cationic protein (s-ECP) and urinary EPX assays. All subjects attended the outpatient clinic every 3 months, irrespective of the treatment prescribed following inclusion in this investigation. At baseline, urinary EPX concentrations were higher in children with asthma and those with chronic cough than in controls (mean 171.1 and 131.3, respectively, vs. 60.2 microg/mmol creatinine, P < 0.001). CC children had lower eosinophil counts (0.25 vs. 0.39 x 10(9)/L, P < 0.02) than those with asthma. There was no significant difference between the AC and CC groups in urinary EPX and s-ECP levels. s-ECP concentrations were significantly higher (P < 0.01) in atopic vs. nonatopic patients (44 vs. 29.9 ng/mL), but no significant difference was observed for urinary EPX. Concentrations of urinary EPX were significantly correlated with s-ECP levels (r = 0.24, P < 0.025) and with PBE (r = 0.38, P < 0.01). No correlation was found between urinary EPX values and PFT results. In AC receiving inhaled steroids after the start of the study, there was a significant reduction after 3 months in urinary EPX (-54, P < 0.02). In contrast, there was no significant change in PBE levels. Urinary EPX concentrations are sensitive, noninvasive technique that could be useful to the clinician in the evaluation of manifestations of airway inflammation.

Urinary Eosinophil Protein X in Children with Atopic Asthma

“…All subjects included in our study had stable well-controlled asthma, as evidenced by a median cumulative symptom score of only 17 of a maximum of 252. Conflicting data have been published on the association between uEPX/c and pulmonary function tests [21, 23]. We found a significant negative correlation between FEV 1 and uEPX/c.…”

“…Urine samples were not all obtained at the same time of the day. Since the start of our study, it became evident that a circadian rhythm of uEPX/c with lowest levels at 7 p.m. and highest at 7 a.m. in both asthmatic and healthy controls exists [23, 29–31]. Hence, diurnal variability may have introduced scatter of uEPX, thus weakening a possible correlation.…”

Urinary Eosinophil Protein X in Childhood Asthma: Relation with Changes in Disease Control and Eosinophilic Airway Inflammation

“…A relation with asthma symptoms and lung function has been shown, and uEPX increases significantly during asthma exacerbations [7–9]. A reduction in uEPX has been reported after starting inhaled corticosteroids [10]. Therefore, it has been suggested that measuring urinary EPX may be useful for monitoring the effect of ICS in asthma [3, 10, 11].…”

Monitoring the allergic inflammation

“…Below I will discuss some of the advantages and disadvantages of measuring ECP in serum/plasma and sputum and also discuss the current evidence that ECP may be a useful addition to the diagnostic armamentarium for monitoring and characterization of disease activity in the allergic patient. I will also discuss the emerging evidence that seems to show that urine measurement of EPX/EDN may be an alternative to ECP measurements in blood as a reflection of eosinophil turnover and activity (43)(44)(45)(46)(47)(48)(49).…”

“…In a search for noninvasive means to monitor eosinophil involving inflammation urine measurement of EPX/EDN has emerged as a promising candidate in particular in children (44,45,48,64). In order to minimize the influence of differences in water dilution of the urine the EPX/EDN levels have to be adjusted by the creatinine concentrations unless 24 h samplings are carried out.…”