Action of a silk fabric treated with AEGIS in children with atopic dermatitis: a 3-month trial.

Irritation of the skin of patients with atopic dermatitis by contact with rough fibres of synthetic or woollen clothes is well known. Therefore, it has been recommended that patients should wear cotton clothes. However, cotton also consists of rough fibres able to irritate the skin, whereas silk is characterized by smooth fibres without irritating potential. The aim of our study was to evaluate the clinical effect of Dermasilk- a special silk fabric (sericin-free silk treated with AEGIS AEM5772/5 which has antibacterial properties) - in children with atopic dermatitis. A total of 22 children with mild-to-moderate atopic dermatitis were recruited for a study period of 3 months. All of them received three different tube-fabrics - Dermasilk, sericin-free silk fabric without AEGIS AEM 5772/5 and cotton, covering the cubital region. Patients were advised to wear the Dermasilk fabric all day long during the whole study period on one arm, whereas the sericin-free AEGIS-free silk tube had to be used during the first 2 wk only on the other arm followed by the use of the cotton tube for the rest of the study period. Evaluation of the local SCORAD score was carried out at the beginning of the study, after 2, 4, 8 and 12 wk. A significant reduction of the local SCORAD index of the Dermasilk covered arm was observed after 4, 8 and 12 wk in comparison with the cotton-covered arm score [median (quartile 1-quartile 3)] 6.5 (5-8) vs. 8 (7-9), p < 0.002; 6 (5.25-7.75) vs. 8 (7-9), p < 0.0001; and 6 (5-6) vs. 8 (7.25-10), p < 0.0001. The use of Dermasilk has a significant beneficial effect in atopic dermatitis because of the non-irritating properties of silk as well as the antibacterial capacity of AEGIS AEM 5772/5.

Predictors of lung function in infants at high risk of atopy: effect of allergen avoidance.

Children of atopic parents are recognised as being at higher risk of developing bronchial asthma, drawing the attention of prevention strategies towards this population. Due to recent advances, lung function abnormalities in asthmatic children may now be measured early in life. The aim ofthis investigation was to examine possible predictors of lung function development in a sub sample of high-risk infants who took part in an allergy avoidance study In 60 babies of atopic parents, measurements of upper airways inflammation were performed at 4 weeks of age, respiratory symptoms were assessed at 6 and 12 months of age, and lung function (Vmax, FRC) was measured at 18 months by the rapid thoracoabdominal compression technique. Twenty-eight babies were enrolled in an allergen avoidance program, and 32 recruited as controls. No significant differences were detected for V'max,FRC between the intervention group (mean 331 ml s(-1)) and the control group (359 ml s(-1)), P = 0.382. A multiple linear regression model could explain levels of V'max FRC by weight gain since birth (beta = -35.35 ml s(-1) kg(-1), P = 0.022) and by eosinophilic cationic protein (ECP) (beta = -0.95 ml s(-1) microl(-1), P = 0.044), but not by intervention. Lung function measured at the age of 18 months in high-risk children is associated with weight gain and nasal ECF.

Ambient ozone exposure is associated with eosinophil activation in healthy children.

BACKGROUND: Eosinophil activation is characteristic for allergic airways disease. However, eosinophilic airways inflammation has also been observed subsequent to ambient ozone exposure. METHODS: For a population sample of 877 children living at nine sites with different ozone exposure we measured urinary eosinophil protein X (U-EPX) as a marker of eosinophil activation. U-EPX was determined from a single spot urine sample during autumn 1997. Children were participants in a longitudinal study of ozone effects on lung function. RESULTS: The 5-95% percentiles of ozone exposure (30-day mean before test) were 11.8-51.5 p.p.b. (mean: 31.6 ppb). U-EPX was measured by radioimmunoassay and expressed as ratio to urinary creatinine (microg EPX/mmol creatinine). Log transformation was performed to achieve a normal distribution. LogU-EPX was associated with gender, a diagnosis of asthma and atopy (skin test sensitivity to any of seven aeroallergens). LogU-EPX increased with ozone exposure for all children. The medians of LogU-EPX according to the first-fourth quartiles of ozone exposure were: 1.82, 1.88, 1.95 and 2.03. For 172 non-asthmatic children who had spent the whole summer at their site corresponding figures were 1.57, 1.78, 2.07 and 2.13. In a multivariate model with logU-EPX being the dependent variable and adjusted for gender, site and atopy, ozone was found to be significant (estimate: 0.007 microg/mmol creatinine per ppb ozone; SE:0.02; P < 0.001). CONCLUSION: Our observation supports the hypothesis that ozone in healthy children is associated with eosinophil inflammation, most likely in the airways.

Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children.

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. METHODS: We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. RESULTS: One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). CONCLUSIONS: At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in characterizing the phenotype of a single patient.

Eosinophil cationic protein and eosinophil protein X in the nasal lavage of children during the first 4 weeks of life. SPACE Collaborative Study Team.

Eosinophil cationic protein (ECP) and eosinophil protein X (EPX) are well established as markers of eosinophil activation. We analyzed ECP and EPX concentrations in nasal lavage fluids (NALF) of 378 neonates during their first 4 weeks of life. Inclusion criteria were a positive history of parental allergy and a positive skin prick test or specific IgE (RAST class > or = 2) against at least one out of a panel of common aeroallergens in one or both parents. Twenty-four infants with no history of parental allergy were used as controls. A volume of 2 ml of 0.9% saline was instilled into each nostril and immediately recovered by a suction device. ECP and EPX were analyzed by radioimmunoassay. In 65 samples of three consecutive lavages, EPX was detected in nine samples (13.8%) in the control group, whereas it was detected in 197/360 samples (54.7%) in the study population. The corresponding figures for ECP were 17/65 (26.2%) in the control group and 173/365 (47.4%) in the study group. Both proteins showed a skewed distribution (median/5-95th percentiles for ECP: 0 microg/l [0-69.4] and EPX: 6.6 microg/l [0-73.2]). The differences between the control group and the study group were statistically significant, regardless of the allergic disease of the parents. In children of allergic parents, activation proteins of the eosinophil granulocyte are released on the nasal mucosal surface in about 50% of the studied population at the age of 4 weeks. This early onset of eosinophil activation in the nasal respiratory epithelium may reflect a genetic predisposition to allergy or early exposure to allergens.

The relationship of eosinophil granule proteins to ions in the sputum of patients with cystic fibrosis.

Increased sputum levels of eosinophil granule proteins have been reported despite normal eosinophil numbers in peripheral blood and in the lung in cystic fibrosis (CF). Mechanisms of eosinophil priming and activation are still unclear in CF. In the present study we investigated whether ion concentrations in the sputa of CF patients are related to eosinophil activity. We assessed concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX), major basic protein (MBP) and ions (Na+, Cl-, Ca2+, Mg2+) in sputum samples of 29 children with CF as well as in 10 controls with bronchial asthma. Patients with CF demonstrated significantly higher levels of ECP, Na+, Cl- and Ca2+ levels than asthmatics (P < 0.04, P < 0.0001, P < 0.0001, P < 0.02). No differences were seen between concentrations of EPX and Mg2+ in the two groups. In CF, eosinophil granule proteins correlated significantly with Ca2+ and Mg2+ concentrations (ECP, P < 0.0001, r = 0.65, P < 0.0001, r = 0.66; MBP, P < 0.03, r = 0.41, P < 0.03, r = 0.42), furthermore inversely with Cl- concentrations (ECP, P < 0. 0003, r = - 0.63; EPX, P < 0.02, r = - 0.45; MBP, P < 0.03, r = - 0. 41) but not with Na+ levels. ECP, Na+ and Cl- were also correlated with lung function variables (FVC, P < 0.04, r = - 0.38, P < 0.02, r = 0.44, P < 0.03, r = 0.41; FEV1, P < 0.007, r = - 0.49, P < 0.006, r = 0.5, P < 0.008, r = 0.48; MEF50, P < 0.003, r = - 0.54, NS, P < 0.03, r = 0.42; MEF25, P < 0.039, r = - 0.4, P < 0.005, r = 0.51, P < 0.05, r = 0.37). Our results demonstrated a significant relationship of eosinophil degranulation and ions in CF, indicating that ion composition in CF sputa may be at least partly be responsible for high levels of eosinophil products despite low eosinophil numbers.

Eosinophil-derived proteins in nasal lavage fluid of neonates of allergic parents and the development of respiratory symptoms during the first 6 months of life. Collaborative SPACE team. Study on the Prevention of Allergy in Children in Europe.

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. METHODS: We studied upper-airways inflammation by nasal lavage in a cohort of 397 infants within the first 4 weeks of life. They participated in an international multicenter study on the prevention of allergy in Europe (SPACE-Biomed II Program). A volume of 2 ml of prewarmed 0.9% saline was instilled into each nasal cavity and immediately re-collected by a suction device. The average recovery was 502 microl (SD: 311 microl). The concentrations of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were determined by RIA analysis. RESULTS: ECP was detectable (>2 microg/l) in 47% of samples (173/365) and EPX (>3 microg/l) in 54.7% (197/360). Children with a doctor's diagnosis of a wheezy bronchitis within the first 6 months of life (n = 40) had significantly higher ECP and EPX concentrations in the nasal lavage at 4 weeks of age (median ECP: 14 microg/l; 5-95th percentile: 0-122.4 microg/l) than children without such diagnosis (median ECP: 0 microg/l; 5-95th percentile: 0-86.6 microg/l; P<0.05). Corresponding figures for EPX were 12.14 microg/l (0-148.98 microg/l) vs 7.5 microg/l (0-81.46 microg/l; P<0.05). No associations between nasal ECP/EPX and the development of food allergy or eczema were observed. CONCLUSIONS: Increased nasal ECP and EPX in the first 4 weeks of life are associated with wheezing in 6-month-old infants at increased risk of atopic disease. We suggest that this might be related to a general tendency for a Th2 cytokine pattern in these young infants and subsequent trafficking of eosinophils into the nasal mucosa, or it might be a consequence of intrauterine allergen exposure.

Urinary eosinophil protein X in children: the relationship to asthma and atopy and normal values.

BACKGROUND: In epidemiologic studies, it may be difficult to identify children with bronchial asthma. Since this is the most common chronic respiratory disease in childhood, and its prevalence is still increasing, reliable methods for identification of asthmatic children are required. This study evaluates the use of urinary eosinophil protein X (U-EPX) in epidemiologic studies in identifying atopic and asthmatic children. METHODS: U-EPX was measured in 877 Austrian schoolchildren. The skin prick test (SPT) was performed with eight common aeroallergens, and established questionnaires were used to assess respiratory symptoms. RESULTS: Of our cohort, 2.8% reported physician-diagnosed asthma, 5.1% reported wheezing within the last 12 months, and 24.1% were found to be atopic. In children with physician-diagnosed asthma, as well as in atopic children (positive SPT), median U-EPX levels were significantly higher than in healthy subjects (142.8 and 89.6 vs 63.9 microg/mmol creatinine, P<0.0001 and P<0.0001, respectively). In addition, perennial sensitization to inhalant allergens resulted in higher U-EPX levels than did seasonal sensitization. The odds ratio for U-EPX levels over the 90th percentile was significantly elevated for asthma, for wheezing, for nocturnal cough, and for breathlessness at exercise, as well as for seasonal and perennial sensitization. Pulmonary function was negatively related to U-EPX levels. CONCLUSIONS: Measurement of U-EPX, which can be obtained easily, may be helpful in diagnosing both asthma and atopy in children. However, there is a great overlap between controls and symptomatics, a fact which reduces the sensitivity of U-EPX in determination of the prevalence of asthma in epidemiologic studies.

Culture conditions for the detection of allergen-specific T-cell reactivity in cord blood: influence of cell number.

Raised T-cell proliferation of cord blood mononuclear cells (CBMC) in response to various ingestant and inhalant allergens has been reported in newborns, suggesting a prenatal allergen contact. In general, for in vitro proliferation assays a concentration of 50 x 10(3) or 100 x 10(3) cells/well are used. The aim of this study was to analyze whether cell concentration influences T-cell reactivity in cord blood cells and to study differences of T-cell reactivity triggered by inhalant and ingestant allergens. CBMC from 51 neonates (34 females: 22 with and 29 without a family history of allergy, i.e. FH+ or FH-) were incubated with interleukin-2 (IL-2), beta-lactoglobulin (beta-LG), ovalbumin (OVA), house dust mite allergen Dermatophagoides pteronyssinus (Der p 1), and timothy grass allergen Phleum pratense (Ph1 p 1) for 7 days. The cell concentration ranged from 6.25 x 10(3) to 100 x 10(3) cells/well. Proliferation was assessed by incorporation of [3H]-thymidine and was expressed as counts per minute (c.p.m.). In unstimulated cells, a decreasing cell concentration paralleled a steep drop of background activity. In response to IL-2, a decreasing cell concentration led to a slow decrease of c.p.m. The corresponding mean stimulation indices (SI) were 9, 32, 77, 47, and 21 for 100 x 10(3), 50 x 10(3), 25 x 10(3), 12.5 x 10(3), and 6.25 x 10(3) cells/well, respectively. In addition, the highest number of positive proliferative responses to specific allergens were obscured at lower cell concentrations. For beta-LG, the maximal number of positive responses were obtained between 25 x 10(3) (n = 44) and 12.5 x 10(3) (n = 46) cells/well, for OVA at 25 x 10(3) (n = 3) cells/well, for Der p 1 at 50 x 10(3) (n = 5) cells/well, and for Ph1 p 1 between 25 x 10(3) and 12.5 x 10(3) (n = 5) cells/well. Positive proliferation in at least one of the tested assays was observed in 100% of samples in response to beta-LG, in 22% in response to Ph1 p 1, and in 14% in response to OVA and Der p 1. T-cell reactivity did not differ between samples of newborns with or without a family history of atopy. Therefore, sensitivity of T-cell proliferation measurement is highly influenced by background proliferation of unstimulated cells. Hence, proliferation assays with lower cell numbers unmask T-cell reactivity in response to ingestant and inhalant allergens. We suggest the use of concentrations of 12.5 x 10(3)-50 x 10(3) cells/well in proliferation experiments.

Major basic protein, but not eosinophil cationic protein or eosinophil protein X, is related to atopy in cystic fibrosis.

Increased eosinophil granule proteins have been described in serum and sputum samples of patients with cystic fibrosis (CF). It has been assumed that eosinophil degranulation is enhanced in atopic subjects - as in asthmatics. Since in CF no differences in eosinophil cationic protein (ECP), eosinophil protein X (EPX), and eosinophil peroxidase between atopic and nonatopic subjects have been detected, we investigated whether major basic protein (MBP) is increased in serum and sputum samples derived from atopic (n = 14) compared with nonatopic CF subjects (n = 26). In CF patients, high mean serum (sputum) levels of ECP 29.7 microg/l (2.7 mg/l), EPX 53.7 microg/l (7.9 mg/l), and MBP 984.6 microg/l but low sputum MBP levels (57.4 microg/l) were measured. In addition, in serum and in sputum samples, a significant correlation between MBP and ECP (P<0.03 and P<0.0001, respectively) or EPX (P<0.05 and P<0.0004, respectively) was detected. By subdivision of the patients into allergic and nonallergic subjects, significant differences were found for serum MBP values only(mean 1382.2 microg/l vs. 770.5 microg/l; P<0.0001), but not for ECP or EPX serum levels or for eosinophil proteins in sputum. Although no differences between atopic and nonatopic CF patients in ECP and EPX were found, serum MBP levels were higher in patients sensitized to inhalant allergens than in nonsensitized subjects. These results indicate differential release of eosinophil granule proteins in peripheral blood from eosinophils, and they also indicate that MBP in serum likely is to be a better discriminator of atopy in CF.

In vivo histamine release during the first minutes after deliberate sting challenges correlates with the severity of allergic symptoms.

In this study, deliberate sting challenge was investigated as a method for estimating the severity of anaphylactic reactions in bee venom-sensitized subjects. Twenty-one patients with previous anaphylactic reactions to field bee sting were subjected to a deliberate sting challenge (n = 32). To document anaphylactic reactions, plasma histamine levels were measured before, and then 1 and 2 min after, bee sting challenge. Eleven patients were re-challenged after 3-5 weeks. On 18 occasions, sting challenges caused no systemic reactions, in seven cases reactions were mild, in five moderate and in two severe. In all children showing systemic reactions, significant increases of plasma histamine were measured after 2 min. The results correlated significantly with clinical scores but not with skin prick test or with specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies against bee venom. In patients developing local reactions only, no increase of plasma histamine was detected. The relative amount of released histamine correlated significantly with the severity of clinical symptoms. Significant histamine release occured during the first 2 min after sting challenge in children with subsequent systemic reactions and the severity of these subsequent anaphylactic reactions correlated with plasma histamine concentrations. The measurement of plasma histamine levels in the first minutes after challenge test may therefore be used as an objective marker of a potential systemic reaction.

Lack of relationship between eosinophil cationic protein and eosinophil protein X in nasal lavage and urine and the severity of childhood asthma in a 6-month follow-up study.

BACKGROUND: Recent studies suggest that eosinophil cationic protein (ECP) and eosinophil protein X (EPX) may be valuable markers of airway inflammation in various body fluids of asthmatic children. Most of these studies have relied on a single measure of inflammatory markers. OBJECTIVE: We measured ECP and EPX in nasal lavage fluids (NALF) and urine samples in children with asthma over a 6-month period to study the relationship between inflammatory markers and clinical severity. METHODS: Fourteen children with mild persisting asthma (mean age 11.7 years, SD 2.2) were recruited. All patients were on therapy including inhaled steroids. For a 6-month period asthma severity was monitored by at least monthly physical examination and pulmonary function tests. Daily morning and evening PEF, asthma symptoms and medication were recorded in diaries for the whole study period. Telephone interviews were performed between visits and additional visits were done in case of an increase in asthmatic symptoms or drop of PEF values under 80% of best value. An exacerbation was defined by a fall of FEV1 > 10% and an increase in asthma symptoms and additional need of beta2-agonist. NALF and urine samples were obtained at each visit and analysed for ECP (NALF only) and EPX. RESULTS: Mean observation time was 186.4 days (SD 19.8). Thirteen patients completed the study. During the study period 11 exacerbations were observed in six patients. No significant associations between PEF, PEF variability (amplitude % of mean), daily symptoms, additional beta2-agonist, FEV1 and MEF50 and nasal ECP, nasal EPX and urinary EPX were found. However, at exacerbations an average increase of nasal ECP (9.3 vs 50.3 microg/L) and EPX (nasal EPX 36.4 vs 141.7 microg/L, urinary EPX 46.4 vs 74.1 microg/mmol creatinine) was observed. CONCLUSION: Serial measurements of ECP and EPX in NALF and urine samples do not provide additional information for the practical management in monitoring childhood asthma.

Assessment of eosinophil granule proteins in various body fluids: is there a relation to clinical variables in childhood asthma?

BACKGROUND: The eosinophil plays a central role in the inflammatory process in bronchial asthma. Recent studies have indicated that the assessment of eosinophil-derived proteins in various body fluids could be used for monitoring disease activity of childhood asthma. Till now, no study exists which compared the levels of eosinophil-derived proteins in various body fluids such as serum, nasal lavage fluid (NALF) and urine. OBJECTIVE: To investigate whether eosinophil granule proteins in different compartments were correlated and whether there is a relationship between disease activity, pulmonary function and bronchial hyperreactivity. METHODS: Twenty-eight children with atopic bronchial asthma were recruited. Serum, NALF and urine samples were obtained and assessed for eosinophil cationic protein (ECP) and eosinophil protein X (EPX). The levels of eosinophil proteins were analysed for a relationship with lung function variables, bronchial hyperreactivity and disease activity. Eleven healthy control subjects were used as controls. RESULTS: Median ECP and EPX concentrations in serum (31.4 and 74.8 microg/L vs 15.8 and 24.3 microg/L, respectively), NALF (9.9 and 44. 9 microg/L vs 0 and 2.5 microg/L, respectively) and urine (49.4 vs 16.5 microg/mmol creatinine) were significantly raised in children with bronchial asthma compared with healthy control subjects. In addition, ECP and EPX levels in serum and urine samples were significantly higher in symptomatic patients compared with asymptomatic subjects with asthma. Although no relationship between eosinophil-derived proteins in serum, NALF or urine and the level of nonspecific bronchial hyperreactivity could be detected, the concentrations of EPX in serum and urine were correlated with variables of pulmonary function. CONCLUSION: Our findings demonstrate increased eosinophil activity in serum, NALF and urine derived from children with bronchial asthma. Due to the relationship between levels of eosinophil proteins in serum/urine samples and lung function, as well as significant concentration differences between symptomatic and asymptomatic asthmatic children, the assessment of eosinophil proteins in serum or urine samples appear to be more appropriate in monitoring disease activity than measurement of ECP or EPX in NALF. Thus, the determination of serum ECP/EPX or urinary EPX may be preferentially used in monitoring eosinophilic inflammation in childhood asthma.

Monitoring of disease activity by measurement of inflammatory markers in atopic dermatitis in childhood.

Serum levels of soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule (ELAM-1), and eosinophil cationic protein (ECP) were measured in 20 patients with atopic dermatitis before and after 4 days' treatment with prednisolone p.o. as well as in 16 healthy, nonatopic controls. Before steroid treatment, patients with atopic dermatitis demonstrated significantly higher serum levels of sIL-2R, ICAM-1, and ECP than healthy controls (P < 0.001), whereas ELAM-1 levels were not different between the groups. After 4 days of steroid treatment, clinical improvement was associated with a decrease of sIL-2R (P < 0.003), ICAM-1 (P < 0.004), and ECP serum levels (P < 0.003), but ELAM-1 levels remained unchanged. Both serum ECP and sIL-2R levels were significantly correlated with disease severity before as well as after steroid treatment. Changes of sIL-2R concentrations were strongly related to the changes of ECP levels. In addition, changes of serum sIL-2R and ECP levels in percentage were correlated with clinical improvement. These results indicate that the determination of sIL-2R and ECP serum levels may be useful in monitoring disease activity in atopic dermatitis in childhood, especially in treatment trials.

Urinary eosinophil protein X in relation to disease activity in childhood asthma.

The clinical use of urinary eosinophil protein X (U-EPX) measurements in monitoring inflammation in childhood asthma was investigated. U-EPX and pulmonary function were assessed in 80 children with bronchial asthma and 24 healthy, age-matched controls. In addition, 14 patients with asthma were re-examined after 1-2 months. U-EPX levels were increased in children with asthma compared with controls (median 68.4 vs 35.3 micrograms/mmol creatinine; P < 0.0001). In addition, U-EPX levels were higher in symptomatic than in asymptomatic patients (median 123.5 vs 48.9 micrograms/mmol creatinine; P < 0.0001) independent of treatment modalities (i.e., inhaled steroids or disodium cromoglycate) or atopy (median 65.1 vs 86.0 micrograms/mmol creatinine). Furthermore, U-EPX levels were significantly correlated with pulmonary function. During the follow-up period, changes in U-EPX values were significantly related to changes in pulmonary function. In conclusion, our findings demonstrate that eosinophil activation can be measured in urine in childhood asthma. Concentrations of U-EPX are related to disease activity and pulmonary function, as shown in both cross-sectional and longitudinal analyses, but are independent of atopy and treatment modalities. Measurement of U-EPX may be useful in assessing the inflammatory process and therefore in the management of childhood asthma.