Eosinophil soluble protein levels, eosinophil peroxidase and eosinophil cationic protein in asthmatic patients.

Eosinophil granular proteins are useful eosinophil activation markers in asthmatic patients. In this study, eosinophil peroxidase (EPO) and eosinophil cationic protein (ECP) levels were assessed in different stages of bronchial asthma in 123 patients suffering from intrinsic (n = 42) and extrinsic (n = 81) asthma, with the aim of evaluating the difference in the protein levels between both types of asthma and their importance as a severity marker of the disease. The geometric mean serum level of EPO was 12.3 +/- 2.17 ng/ml (mean +/- SD) in controls, and 38.6 +/- 3.4 ng/ml in the asthmatic patients. Mean ECP levels were 13.22 +/- 1.11 ng/ml in controls and 30.5 +/- 2.38 ng/ml in patients. Depending on the asthma severity, the EPO levels were 30.4 +/- 4.35, 38.7 +/- 5.29, and 54.46 +/- 9.46 ng/ml in mild, moderate and severe asthmatics, respectively, with the differences being significant between the groups of patients with mild and severe asthma (p < 0.001). ECP levels were 24.23 +/- 3.37 in mild, 31.69 +/- 4.21 in moderate, and 37.61 +/- 4.52 ng/ml in severe asthma. There were significant differences in ECP levels between mild and moderate asthma (p < 0.001) and between mild and severe asthma (p < 0.001). Peripheral eosinophil count was 157 +/- 20 eosinophils/mm3 in controls, 334 +/- 35 eosinophils/mm3 in mild asthmatics, 510 +/- 87 eosinophils/mm3 in moderate asthmatics and 658 +/- 72 eosinophil/mm3 in severe asthmatics, with significant differences between all groups (p < 0.05-p < 0.001). Serum EPO and ECP levels and peripheral eosinophil count were significantly greater in patients with active asthma than in patients with silent asthma (p < 0.001). Significant negative correlations (p < 0.001) were found between serum EPO levels and FEV1 (rs = -0.30), MEF25-75 (rs = -0.33), MEF50 (rs = -0.34). There was also a significant (p < 0.001) and negative correlation between ECP levels and FEV1 (rs = -0.31), MEF25-75 (rs = -0.31), MEF50 (rs = -0.32). A good positive correlation was found between peripheral eosinophil count and EPO levels (rs = 0.80, p < 0.001), and ECP levels (rs = 0.67, p < 0.001). We also found a significant positive correlation between clinical score and peripheral eosinophil count (rs = 0.54, p < 0.001), EPO levels (rs = 0.46, p < 0.001) and ECP levels (rs = 0.52, p < 0.001).     

Changes in the peripheral eosinophil count in patients with acute eosinophilic myocarditis

In many cases, the diagnosis of eosinophilic myocarditis is suggested by an elevated peripheral blood eosinophil count. However, no detailed studies have been performed on the sequential changes in the initial peripheral blood eosinophil count over the course of the disease. We measured the peripheral blood eosinophil count at the time of presentation in eight patients with eosinophilic myocarditis proven by endomyocardial biopsy and intermittently thereafter. The eosinophil count at the time of onset was 500/mm³ in four patients, 500/mm³ but 1000/mm³ in three patients, and 1000/mm³ in one patient. In three of the four patients with an initial eosinophil count of 500/mm³, an increase to 500/mm³ occurred 7–12 days after the onset. The remaining patient did not develop peripheral eosinophilia. In conclusion, in the early stage of eosinophilic myocarditis, peripheral hypereosinophilia is not present initially in some patients, and may not develop during the course of the illness in a subset of these patients.     

Serum concentrations of eosinophil cationic protein and eosinophils of patients with Kimura's disease.

BACKGROUND: To clarify the role of eosinophils in the pathogenesis of Kimura's disease and the values of measuring serum levels of eosinophil cationic protein (ECP) for monitoring disease activity might be very important, but there are few reports about this matter. METHODS: A total 14 serum and 7 tissue samples from patients with Kimura's disease were studied. The concentrations of ECP and cytokines (interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 5 (IL-5)) in sera from patients with Kimura's disease were measured by enzyme-linked immunosorbent assay (ELISA). The density of eosinophils and the degree of activation of eosinophils in the tissue were also studied immunohistochemically. RESULTS: The concentration of ECP in sera from patients with Kimura's disease was significantly higher than that in the control group (p<0.05). At the time of the remission, a significant decrease of ECP was observed. In interfollicular areas, most infiltrated eosinophils were positive for EG2 antibody (64.0-94.0%) and the mean percentage of EG2-positive eosinophils was 75.7%. The concentrations of IL-4, GM-CSF, and IL-5 in sera from patients with Kimura's disease were within normal ranges or below the detectable level in all sera examined. CONCLUSIONS: Our findings suggest that eosinophils play an important role in the pathogenesis of Kimura's disease and ECP may be used as an additional parameter of disease activity.     

Serum measurement of eosinophil cationic protein in the management of asthma

Asthma is a disease characterized by chronic eosinophilic inflammation of the airways. Serum eosinophil cationic protein (ECP) has been increasingly used as a noninvasive inflammatory marker in asthma. The serum ECP level seems to reflect, although indirectly, the intensity of ongoing eosinophilic inflammation of the airways and respond sensitively to intervention, whereas it is unlikely to be useful for establishing the diagnosis of asthma in an individual patient. Monitoring of serum ECP could be of utility in the long-term follow-up of asthmatic patients. However, further longitudinal studies are required to establish the role of serum ECP measurement in the treatment modulation in asthma.     

Serum eosinophil cationic protein and bronchial responsiveness in pediatric and adolescent asthma patients.

BACKGROUND: Serum eosinophil cationic protein (ECP) has been promoted as a marker of inflammatory activity in bronchial asthma. Bronchial responsiveness, measured either by inhaling pharmacologically active substances such as histamine or methacholine, or by applying physical stimuli such as the hyperventilation of cold dry air, is also considered to be an indirect marker of bronchial inflammation. OBJECTIVES: In this study, we investigated the possible relationship between serum ECP and bronchial responsiveness to both cold dry air and histamine in presently symptom- and medication-free pediatric and adolescent asthma patients. SUBJECTS: Thirty-six children and adolescents with atopic asthma were studied. METHODS: On 2 consecutive days, bronchial responsiveness was assessed nonpharmacologically by cold dry air and pharmacologically by histamine in random order. Blood samples for determination of ECP were collected before each challenge. RESULTS: Serum ECP levels correlated with neither cold dry air-induced changes in FEV1 nor the provocation concentrations of histamine causing a 20% fall in FEV1. Subjects with bronchial hyperresponsiveness to cold dry air and histamine had somewhat higher levels of serum ECP than subjects with normal responses, but these differences were insignificant. CONCLUSIONS: Our results indicate a lack of relationship both between serum ECP and bronchial responsiveness to cold dry air and between serum ECP and bronchial responsiveness to histamine.     

Serum levels of eosinophil cationic protein and eosinophils in asthmatic children during a course of prednisolone therapy

Eosinophils play an important role in the inflammatory events of allergic asthma. Serum eosinophil cationic protein (ECP) is a marker of disease activity and of treatment efficacy in bronchial asthma. To understand the role of ECP concentrations in disease activity of acute asthma, we determined changes in serum concentrations of ECP elaborated by activated eosinophil before and after prednisolone therapy. Circulating levels of ECP in 15 normal control subjects, and in sera of 20 asthmatic children who were allergic to house dust mites, were measured during an acute exacerbation and when the children were in stable condition, using commercially available assay kits. The mean concentrations of serum ECP were significantly higher during an acute asthma exacerbation than when the children were stable (26.41 +/- 21.66 microg/L vs 15.74 +/- 11.36 microg/L P < 0.01) or when compared to control subjects (7.50 +/- 1.42 microg/L; P < 0.001). The mean eosinophil counts (EC) during acute asthma attacks (575 +/- 286/mm3) and when stable (467 +/- 204/mm3) were higher than in the control group (181 +/- 164/mm3). The differences were statistically significant among the three groups (P < 0.05). A significant correlation was found between serum levels of ECP and EC (r = 0.788, P = 0.001) in asthmatic children; there were also significant correlations between ECP and EC in nonallergic normal control subjects (r = 0.662; P = 0.007). In conclusion, this study provides further evidence that changes in serum ECP may serve as an objective indicator for clinical activity and results of treatment in allergic asthmatics.     

Decreased serum levels of P-selectin and eosinophil cationic protein in patients with mild asthma after inhaled salbutamol

BACKGROUND: Asthma is a chronic inflammatory disease of the airways associated with selective recruitment of activated eosinophils. P-selectin, a cell adhesion molecule, may be an important controller of the inflammation by mediating selective eosinophil cell influx to the lung. Serum levels of eosinophil cationic protein (ECP) have been used as a marker of eosinophil inflammation, and indirectly as a marker of disease activity of asthma. ECP levels may not be elevated in some patients with asthma, and this fact prompted us to search for additional surrogate markers for monitoring disease activity in asthma. OBJECTIVES: To evaluate whether repeated inhalations of salbutamol, a beta-2-receptor agonist used for bronchodilation, would lead to reduced serum levels of P-selectin and/or ECP. METHODS: Fourteen patients with asymptomatic mild stable asthma were enrolled into a randomised crossover study. Salbutamol was inhaled three times every 3 h. Blood was sampled 4 h after the last inhalation. Nine non-treated healthy volunteers served as control subjects. Serum ECP and P-selectin levels were measured using radioimmunoassay and ELISA, respectively. RESULTS: P-selectin and ECP levels in serum obtained from asymptomatic asthmatics were close to those of the volunteers, and inter-day variability tended to be lower for levels of P-selectin than for ECP. Significant decreases of P-selectin (p = 0.01) and ECP (p = 0.03) were recorded after salbutamol inhalation. There was no association between the changes in ECP and P-selectin levels in serum. CONCLUSIONS: We conclude that decreases in P-selectin and ECP may have different kinetics, suggesting different pathways of action of salbutamol. We judge that P-selectin may be used as a sensitive marker in mild asthma.     

Serum eosinophil cationic protein as a predictor of wheezing after bronchiolitis

We have evaluated the role of eosinophil cationic protein (ECP) concentrations in serum in predicting wheezing after bronchiolitis, during infancy and early childhood. A prospective study at a university hospital serving all pediatric patients in a defined area was designed. Serum ECP concentrations were measured in 92 infants under the age of 2 years on admission for acute bronchiolitis, and 6 and 16 weeks after hospitalization. Nebulized anti-inflammatory therapy was initiated during hospitalization: 32 patients received cromolyn sodium and 32 patients received budesonide for 16 weeks; 30 control patients received no maintenance therapy. The numbers of subsequent physician-diagnosed wheezing episodes and hospital admissions for obstructive airway disease were recorded during 16 weeks of follow-up. At entry, 14 of 92 (15%) children had high (≥16 μg/L) levels of ECP in their serum. During the 16-week follow-up period, this group of patients had significantly more physician-diagnosed episodes of wheezing (86% vs. 43%, P < 0.01) and hospital admissions for wheezing (64% vs. 19%, P = 0.001) than those with serum levels of ECP < 16 μg/L. The number of patients with serum ECP ≥ 8 μg/L was 25 (27%); 76% of this group developed physician-diagnosed wheezing (P < 0.01), and 48% had hospital admissions for wheezing (P < 0.01). Serum ECP levels decreased significantly with respect to time after bronchiolitis and did not differ among the three intervention groups. We conclude that a high serum ECP concentration during the acute phase of bronchiolitis is a specific but insensitive predictor of wheezing after bronchiolitis. Pediatr. Pulmonol. 1997; 23:397–403. © 1997 Wiley-Liss, Inc.     

Serum eosinophil cationic protein (S-ECP) in a population with low prevalence of atopy

The study is a part of the European Community Respiratory Health Survey. A random sample (n = 351) of 20-44-year olds and persons of the same age with asthma-like symptoms or current asthma medication according to a postal questionnaire (n = 95) were studied. Interview was taken, methacholine challenge was done and ECP, total and specific IgE were measured from serum. The median S-ECP value was 8.0 micrograms/l in the random sample. The geometric mean of S-ECP was higher in subjects with, than without atopy (10.2 vs 8.9 micrograms/l, P < 0.01) and in subjects with bronchial hyperresponsiveness (BHR) than in subjects without BHR (9.9 vs 8.0 micrograms/l, P < 0.01). The levels correlated weakly to forced expiratory volume in one second (FEV1) (r = 0.13, P < 0.01) and were not independently correlated with respiratory symptoms, asthma or FEV1 after adjusting for BHR, IgE, sensitisation and smoking. Our results indicate that the level of eosinophil activation is low in a population with a low prevalence of atopy, even when BHR is common.     

Nasopharyngeal eosinophil cationic protein in bronchiolitis

A prospective 4-month follow-up of children hospitalized with bronchiolitis revealed that high concentrations of eosinophil cationic protein (ECP) in nasopharyngeal aspirates (NPA) are predictive of wheezing after bronchiolitis. In the 29 patients who received no anti-inflammatory therapy the median concentration of NPA ECP was 882 ng/g in those with physician-diagnosed wheezing and 154 ng/g in those without subsequent physician-diagnosed wheezing (P = 0.02). The NPA ECP concentrations of the whole study group of 88 children with and without subsequent hospital admissions for wheezing were 531 and 299 ng/g, respectively (P = 0.02). At entry the children with negative viral findings had significantly higher concentrations of respiratory tract ECP than those with positive viral findings (515 vs. 240 ng/g; P = 0.01). The concentration of ECP in respiratory secretions decreased significantly after bronchiolitis (P = 0.01) provided that no new viral or mycoplasmal infection occurred. NPA ECP values decreased in relation to time regardless of whether anti-inflammatory therapy was used or not. Children with high concentrations of respiratory tract ECP seemed to benefit from anti-inflammatory therapy with nebulized cromolyn sodium or budesonide; both drugs significantly decreased the number of subsequent physician-diagnosed bronchial obstructions (P = 0.0006), and they tended to decrease the number of hospital admissions for wheezing (P = 0.08). Our results suggest that high concentrations of ECP in respiratory tract secretions in children with bronchiolitis reflect the presence of eosinophilic inflammation also seen in asthma. Pediatr. Pulmonol. 1997;24:35–41. © 1997 Wiley-Liss, Inc.     

Eosinophilic myocarditis associated with dense deposits of eosinophil cationic protein (ECP) in endomyocardium with high serum ECP.

A case of eosinophilic myocarditis following high serum levels of eosinophil cationic protein (ECP) is described. A 27 year old woman was admitted with New York Heart Association (NYHA) class III congestive heart failure. A haematological study showed hypereosinophilia with degranulation and vacuoles; the total eosinophil count was 7980/ml and the ECP serum concentration was noticeably high at 150 ng/ml. Endomyocardial biopsy from the right ventricle showed infiltration of eosinophils and dense deposits of ECP in the endocardium as well as the myocardium. Steroid treatment returned the total eosinophil count and serum ECP to normal, with satisfactory improvement in clinical features. Eosinophilia may cause cardiac damage, and this report confirms that eosinophil degranulation is toxic. Thus, serum ECP seems to be a reliable indicator for diagnosis and for determining treatment parameters of eosinophilic myocarditis.     

Blood eosinophil leucocytes and eosinophil cationic protein. Diurnal variation in normal subjects and patients with bronchial asthma

Normal subjects and patients with bronchial asthma showed a similar diurnal variation in blood eosinophil count and serum eosinophil cationic protein concentration. The blood eosinophils showed the highest count during the night whereas serum eosinophil cationic protein showed the highest concentration in the early evening. It is concluded that this may result from a difference in hormonal or other influences.     

支气管哮喘患儿呼出气一氧化氮及血清嗜酸粒细胞阳离子蛋白的变化

目的探讨呼出气一氧化氮(eNO)在支气管哮喘(AS)儿童中的应用,比较eNO和血清嗜酸粒细胞阳离子蛋白(ECP)在AS、AS合并过敏性鼻炎(AR)、慢性咳嗽变异性哮喘(CVA)的不同,寻找适用于儿童AS简便易行的气道炎症监测指标方法.方法 设定50 ml/s呼出气流速,采用电化学法对51例5～14岁患有AS、AS/AR、CVA的患儿,及30例5～14岁正常对照组儿童进行eNO测定,同时测定ECP及第1秒用力呼气容积占预计值百分比(FEV1pred%).结果 AS、AS/AR、CVA三组间eNO、ECP水平均高于对照组(P＜0.01);AS/AR组eNO、ECP水平均高于AS、CVA组(P值均＜0.05),而AS、CVA组间则无明显差异(P＞0.05);AS组eNO与ECP间存在显著相关性(r＝0.64,P＜0.05),但与FEV1间则无明显相关性(r＝0.144,P＞0.05).结论 eNO水平在AS/AR组增高,提示eNO在过敏性体质中高表达.eNO浓度与血清ECP呈正相关,提示eNO可以反映AS患者气道嗜酸性炎症水平.     

Serum eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in childhood asthma: The influence of atopy

The purpose of this study was to determine the value of serum measurements of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in diagnosing asthma in children, and to investigate the influence of concomitant allergic diseases and atopic sensitization, assessed by skin prick tests (SPT), on these markers. ECP and EPX were determined in 36 children with asthma, in 33 children with other symptoms from lower airways disease (OSLA), and in 166 control children. Sixteen children with asthma but no anti-inflammatory therapy had significantly higher concentrations of ECP and EPX (ECP: 27.5 μg/L, P < 0.001; EPX: 59.9 μg/L, P < 0.001) than the control children (ECP: 11.2 μg/L; EPX: 26.2 μg/L). In the 20 children on anti-inflammatory therapy, ECP values were similar to those of controls. The children with OSLA (ECP: 13.6 μg/L, P < 0.01; EPX: 47.2 μg/L, P < 0.001) differed significantly from controls. When using the value of 24.7 μg/L (97.5 percentile in the 68 non-atopic controls) as a pathologic upper limit for ECP, 10 (63%) of the 16 asthmatic children on no maintenance medication, two (10%) of the 20 asthmatics on maintenance therapy, and 11 (33%) of the 33 children with OSLA had high ECP; the same figure was only 18 (11%) in the 166 control children. Both ECP and EPX had a significant association with allergic disorders and with SPT reactivity. In multivariate logistic regression analysis, an elevated ECP was significantly associated with asthma (OR 2.3, 95%Cl 1.1–4.9) and atopic dermatitis (2.9, 1.2–6.9), and an elevated EPX was significantly associated with asthma (2.61, 1.19–5.74) and allergic rhinoconjunctivitis (5.23, 1.46–18.73). We conclude that serum concentrations of both ECP and EPX are higher in asthmatic than in healthy children. However, other allergic diseases, such as allergic rhinoconjunctivitis, atopic dermatitis, and allergic skin sensitization also raise the concentrations of these markers. This limits their usefulness in the diagnosis of childhood asthma. Pediatr. Pulmonol. 1998; 25:167–174. © 1998 Wiley-Liss, Inc.     

Changes in serum eosinophil cationic protein levels after exercise challenge in asthmatic children.

The aim of the present study was to assess the relationship between serum eosinophil cationic protein levels and the severity of exercise-induced bronchoconstriction in asthmatic children. The 48 asthmatic children were divided into exercise-induced bronchoconstriction group and non-exercise-induced bronchoconstriction group. In the exercise-induced bronchoconstriction group, the post-exercise serum eosinophil cationic protein levels were significantly increased as compared with the pre-exercise serum eosinophil cationic protein levels. These results suggested that eosinophil cationic protein may serve as a possible contributor to the pathophysiology of exercise-induced bronchoconstriction in asthmatic children.     

The promoter polymorphism in the eosinophil cationic protein gene and its influence on the serum eosinophil cationic protein level

Asthma is characterized by reversible airway obstruction and airway inflammation. Serum levels of eosinophil cationic protein (ECP) might reflect eosinophilic airway inflammation and asthma activity. However, serum ECP levels are not elevated in some patients with asthma, even when they are symptomatic. In this study, we screened for polymorphisms in the ECP gene and analyzed association between these polymorphisms and asthma and serum ECP levels in 137 Japanese families identified through children with asthma. We identified three polymorphisms (-393C/T, -38C/A, and 124Arg/Thr) in human ECP. We did not find associations between these polymorphisms and asthma by the transmission disequilibrium test. However, we found that serum ECP levels in subjects with the -393T allele were significantly lower than those in subjects with the -393C allele. A reporter construct with the -393T allele showed significantly lower promoter activity than one with the -393C allele. Gel shift assay revealed that C/EBP proteins can bind the -393C/T polymorphic site. These data indicate that C/EBP proteins play an important role in the regulation of ECP and that a significant amount of the variance in baseline serum ECP levels may be explained by the -393C/T polymorphism. Although ECP polymorphisms are not likely to be involved in the development of asthma, measurement of ECP levels for the assessment of asthma activity may be improved when done in combination with genotyping of the -393C/T polymorphism.     

High levels of cord serum eosinophil cationic protein predict the risk of atopy.

BACKGROUND: Transient tachypnoea of the newborn is a transient respiratory disturbance characterized by tachypnoea shortly after birth, which resolves within 2 to 5 days. The basic pathogenetic mechanism is the delayed resorption of the alveolar fluid of which the exact triggering mechanism still remains unknown. An etiological link associated with parenteral history of atopy was proposed by several studies. Some laboratory studies also revealed that serum IgE, eosinophil cationic protein (ECP) and cord IgE were higher among infants with maternal history of atopy. OBJECTIVE: The purpose of this study was to investigate the possible association of parental history of atopy with cord blood ECP and IgE concentrations in infants with transient tachypnoea of the newborn. METHODS: ECP and IgE levels were quantified in cord blood samples of 30 infants who were diagnosed as having transient tachypnoea of the newborn. The control group (N=30) was selected among healthy newborns with similar birth weight and gestational age. RESULTS: Cord blood ECP concentrations were significantly higher in the study group (17.6 microg/L) than in healthy control subjects (7.89 microg/L). In addition, transient tachypnoea of the newborn was more frequent in infants with a family history of atopic disease (p<0.01). Cord blood IgE concentrations were also higher in the study group than the controls (4.1 versus 3.28 mg/L) but the difference was not statistically significant (p>0.05). CONCLUSION: Family history of atopy and elevated levels of cord blood ECP are risk factors for transient tachypnoea of the newborn. In addition cord blood ECP level is a useful marker for predicting the risk of atopy.     

Serum TARC levels are strongly correlated with blood eosinophil count in patients with drug eruptions

Background

This study aims to evaluate the relationship between serum thymus and activation-regulated chemokine (TARC) levels with various clinicopathological conditions in patients with drug eruptions. The value of TARC in diagnosing drug-induced hypersensitivity syndrome (DIHS) was also examined.