Elevated Serum Eosinophil Cationic Protein Research Articles

Simultaneously elevated exhaled nitric oxide and serum-eosinophil cationic protein relate to recent asthma events in asthmatics in a cross-sectional population-based study.

We have reported that increased fraction of exhaled nitric oxide (FeNO), a measure of TH2 -driven airway inflammation, and blood eosinophil count, a marker of systemic eosinophil inflammation, correlated with asthma attacks in a population-based study. To investigate the relation between simultaneously elevated FeNO and serum eosinophil cationic protein (S-ECP) levels and asthma events among asthmatics. Measurements of FeNO (elevated ≥ 25 ppb) and S-ECP (elevated ≥ 20 ng/mL) were performed in 339 adult asthmatics. Asthma events (attacks and symptoms) were self-reported. Simultaneously normal S-ECP and FeNO levels were found in 48% of the subjects. Subjects with simultaneously elevated S-ECP and FeNO (13% of the population) had a higher prevalence of asthma attacks in the preceding 3 months than subjects with normal S-ECP and FeNO (51% vs. 25%, P = 0.001). This was not found for subjects with singly elevated S-ECP (P = 0.14) or FeNO (P = 0.34) levels. Elevated S-ECP and FeNO levels were independently associated with asthma attacks in the preceding 3 months after adjusting for potential confounders (OR (95% CI) 4.2 (2.0-8.8). Simultaneously elevated FeNO and S-ECP levels were related to a higher likelihood of asthma attacks in the preceding 3 months. This indicates that there is a value in measuring both FeNO and systemic eosinophilic inflammation in patients with asthma to identify individuals at high risk of exacerbations. FeNO and S-ECP are markers for inflammation in asthma, but are dependent on different inflammatory pathways and weakly correlated. Simultaneous measurements of both offer better risk characterization of adult asthmatics.

Analyzing Serum Eosinophil Cationic Protein in the Clinical Assessment of Chronic Rhinosinusitis

Eosinophil cationic protein (ECP) is a major granule-derived protein with cytotoxic activity found in eosinophils and has been known as a useful marker of allergic inflammation. In this study, we assessed the clinical significance of ECP in chronic inflammation of the nasal mucosa by evaluating the relationship between eosinophil activity and serum ECP concentration in a cohort of subjects with or without chronic rhinosinusitis (CRS) and allergic rhinitis (AR). We retrospectively reviewed the medical records of 492 subjects and analyzed eosinophil percentage in nasal smears, serum eosinophil counts, serum ECP concentrations, symptom scores, CT scores, the size of nasal polyp, and recurrence of CRS at follow-up. Elevated serum ECP concentration was closely related with higher eosinophil expression in all subject's nasal smears and sera. CRS subjects without AR had a higher percentage of immune cells that were eosinophils compared with control subjects and it was similar to subjects' with AR only or with both CRS and AR. CRS subjects without AR also had significantly higher serum ECP concentrations and eosinophil counts compared with control subjects. Additionally, serum ECP concentration was significantly correlated with CT scores, symptom scores, polyp size, and recurrence rate in CRS subjects without AR. Serum ECP concentration can be used as a marker of local and systemic eosinophil expression. We conjecture that although serum ECP elevation may not be specific in AR, analysis of serum ECP concentration could be particularly useful in estimating the progression and prognosis of CRS.

Churg-Strauss Syndrome: The Clinical Features and Long-term Follow-up of 17 Patients

Churg-Strauss syndrome (CSS) is a rare multi-system vasculitis; some cases have been reported in Korea. The aim of this study is to describe the clinical features, treatment outcome, and long-term follow-up of CSS from a single Korean medical center. Between 1995 and 2004, seventeen patients were diagnosed with CSS at the Department of Medicine of the Samsung Medical Center, Sungkyunkwan University School of Medicine. The diagnosis of CSS is based on the classification criteria of the American Collage of Rheumatology. All patients had asthma. As in other case series, the lung, peripheral nervous system, and skin were the most commonly involved organs. During the active stage of the disease, most of the patients exhibited peripheral blood eosinophilia and an elevated serum eosinophil cationic protein level. Ten patients were treated with pulses of methylprednisolone followed by tapering and cyclophosphamide, and the others were treated with corticosteroids alone. The outcomes after long-term follow-up were generally good. One patient who was refractory to initial treatment died of heart failure during the follow-up period. CSS was highly variable in its presentation and course. The manifestations may range from mild symptoms to life-threatening conditions. The outcome after long-term follow-up was as good as that of previous studies.

Bronchial responsiveness and serum eosinophil cationic protein levels in preschool children with recurrent wheezing

Bronchial hyperresponsiveness is a universally recognized phenomenon of asthma, and increased levels of eosinophil cationic protein (ECP) have been identified in the serum of patients with asthma. To investigate whether enhanced bronchial responsiveness and elevated serum ECP levels are associated with recurrent wheezing in preschool children and to examine the possible relationship between these 2 variables. We recruited 130 children aged 4 to 6 years: 59 with at least 3 episodes of wheezing in the previous year (current wheezers), 38 with a documented history of wheezing before 3 years of age but no subsequent wheezing episodes (past wheezers), and 33 who had never experienced wheezing (nonwheezers). The children underwent methacholine bronchial provocation tests using a modified auscultation method and blood sampling for the measurement of ECP levels. Current wheezers showed greater bronchial responsiveness than past wheezers and nonwheezers, as demonstrated by lower provocation concentrations that caused audible wheeze and lower provocation concentrations that caused a decline in oxygen saturation of at least 5% from baseline. Likewise, current wheezers had higher serum ECP levels than the other 2 groups. Among current wheezers, ECP levels showed a significant negative correlation with provocation concentrations that caused oxygen desaturation and a marginally significant correlation with provocation concentrations that caused audible wheeze. Enhanced bronchial responsiveness and elevated serum ECP levels are associated with recurrent wheezing in 4- to 6-year-old children. These results suggest that wheezing during preschool years may be phenotypically similar to wheezing in older children.

Diagnostic value of skin-prick and patch tests and serum eosinophil cationic protein and cow's milk-specific IgE in infants with cow's milk allergy.

The diagnosis of cow's milk allergy is based on a clinical response to an elimination-challenge test with cow's milk. We studied the usefulness of the skin-prick and patch tests and measurement of cow's milk-specific IgE and eosinophil cationic protein in serum as diagnostic tools for cow's milk allergy in a cohort of 6209 unselected infants followed from birth for the development of cow's milk allergy. Of the 239 infants challenged with cow's milk, 118 showed a positive and 121 a negative response at a mean age of 6.9 months. A positive reaction to a skin-prick test with cow's milk (> or = 3 mm) was seen in 72 (61%) and 29 (24%) infants with positive and negative challenges, elevated serum cow's milk-specific IgE (> or = 0.7 kU/L) in 52 (45%) and 15 (13%) infants, a positive reaction to patch test with cow's milk protein fractions in 26 (26%) and eight (8%) infants, and elevated serum eosinophil cationic protein (> or = 20 microg/L) in 22 (21%) and seven (13%) infants, respectively. Parallel use of the four tests with the above-mentioned cut-off values correctly classified 73% of the infants with a sensitivity of 0.76 and a specificity of 0.67. An immediate reaction to cow's milk challenge correlated with skin prick test positivity and elevated serum milk-specific IgE, and tended to correlate with patch test positivity. No single test or parallel use of the four tests could predict the challenge outcome acceptably in this prospectively followed, unselected cohort of 6209 infants. A positive reaction to one or more tests needs to be confirmed by a challenge test and a negative response to all four tests does not rule out the possibility of cow's milk allergy.

Serum eosinophil cationic protein in asthma of farmers

Objective: There is need for relevant markers of bronchial inflammation in epidemiologic studies of asthma. Serum eosinophil cationic protein (ECP) is a marker of eosinophil inflammation and asthma activity. We have studied serum ECP in atopic farmers with current asthma, in non-atopic asthmatics and in non-asthmatic, non-atopic controls. Methods and results: In a cross-sectional study of a representative sample of 8482 farmers in Norway, asthma was recorded using a self-administered questionnaire; spirometry and serum sampling were performed on all of them. Atopy was screened with Phadiatop and RAST analyses to the mites Lepidoglyphus destructor and Tyrophagus putrescentiae in all asthma cases and controls. All the identified atopics had additional RAST analyses on a set of allergens. Serum ECP was tested in 60 persons with current asthma and atopy (mean 16.2, 95% CI 13.2-19.3), 127 non-atopic asthmatics (mean 9.1, 95% CI 8.0-10.2) and 39 non-atopic controls (mean 5.5, 95% CI 4.0-7.0). ECP levels in atopic asthmatics were associated with number of positive allergens and reduction of FEV1 values. Moreover, the ECP levels were elevated with allergy to swine, cow, D. pteronyssinus, L. destructor, A. siro, T. putrescentiae, timothy grass and the cereal grains: wheat, oat, barley and rye. Conclusion: Serum ECP seems feasible as an indicator of inflammatory activity in epidemiological studies of current allergic asthma, and may help to indicate the importance of specific allergens. Although the ECP values were significantly more elevated in atopic than in non-atopic asthma, elevated serum ECP was not specific for atopic asthma.

Patients with psoriasis have elevated levels of serum eosinophil cationic protein and increased numbers of EG2 positive eosinophils in the duodenal stroma

The occurrence of EG2-positive (EG2+) eosinophils and IgE in biopsy specimens of duodenal mucosa and skin from 39 psoriasis patients was studied, with emphasis on the relation to serum eosinophil cationic protein (ECP), serum IgE and the presence or absence of serum IgA and IgG antigliadin antibodies. Psoriasis patients had significantly elevated serum levels of ECP even after exclusion of five of 37 sera which were Phadiatop positive. The elevated serum ECP was not associated with the presence of IgA or IgG antibodies to gliadin. After exclusion of Phadiatop positive sera the serum IgE values did not differ from those of a group of healthy blood donors. Patients with psoriasis had a pronounced increase of EG2+ cells in their duodenal stroma. Patients without antibodies to gliadin tended to have even more EG2+ cells than those with such antibodies and those with increased duodenal intraepithelial lymphocytes. IgE+ cells were present in most duodenal specimens, and in some specimens there were > 100 IgE+ cells/section. The number of EG2+ cells was increased in lesional skin and, in some patients, also in non-involved skin, but there was a more pronounced increase in EG2 reactivity in the duodenal than in the skin specimens. IgE reactivity was increased both in non-involved and involved skin and was significantly related to the number of IgE-positive cells in the duodenal stroma. The results of this study indicate that the gastrointestinal tract and the eosinophil granulocyte might be involved in psoriasis in a hitherto unknown way.

Elevated Serum Eosinophil Cationic Protein Levels in Cystic Fibrosis, Pediatric Asthma, and Bronchiolitis

Serum levels of eosinophil cationic protein (ECP) may correlate with activity in certain disease states, suggesting that eosinophils and their toxic granular products are involved in the pathogenesis of the disease. The aim of this study was to measure the serum concentration of ECP in patients with cystic fibrosis (CF), pediatric asthma, and viral bronchiolitis. The absolute number of blood eosinophils and IgE levels were determined simultaneously. Serum ECP levels were the highest in CF patients (median, 3101 μg/L, ± 463, N = 18), followed by those with asthma (median, 1113 μg/L, ± 795, N = 10) and those with viral bronchiolitis (median, 1281 μg/L, ± 274, N = 9). Control patients with no infection or lung disease all had ECP levels between 2 and 58 μg/L (median, 3.7 ± 14.7 μg/L, N = 10). The CF patients studied had a significantly higher level of ECP when compared to pediatric asthma and viral bronchiolitis patients (p = 0.008). There was no correlation between the IgE level or absolute eosinophil count and the ECP level. Among the CF patients studied, the forced expiratory volume in 1 second (FEV1) and ECP level did show a significant inverse correlation, (p < 0.01, probability). The finding of elevated ECP levels in CF patients indicates the presence of eosinophil activation in these patients. The correlation between ECP and airflow obstruction suggests a role for activated eosinophils in disease pathogenesis.

Eosinophil cationic protein(ECP) and eosinophil protein X (EXP) concentrations in serum and bronchial lavage fluid in asthma. effect of prednisolone treatment.

Eosinophil granule proteins may contribute to bronchial hyperresponsiveness in asthma. To measure eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in serum and bronchial lavage fluid from 20 asthmatics and 16 control subjects. To assess the effect on these eosinophil proteins of corticosteroid treatment of asthma. To determine whether serum ECP and EPX measured weekly in a longitudinal study for 10 weeks reflected changes in lung function. Eosinophil granule proteins were measured by radioimmunoassay of bronchial wash (BW), bronchoalveolar lavage (BAL) and serum. Eosinophils were elevated in BAL (P < 0.01), BW (P < 0.01) and blood (P < 0.01) from asthmatics compared with control subjects. Eosinophils cationic protein concentration was significantly elevated in BAL (P < 0.05) and BW from asthmatics (P < 0.01) and EPX was increased in BAL (P < 0.05) and BW (P < 0.01). These changes were also reflected in elevated serum ECP (P < 0.01) and EPX (P < 0.01) concentrations in asthmatic subjects. There was no significant difference between subjects receiving prednisolone and the placebo group, but there was a fall in ECP in BW (P < 0.05) and serum (P < 0.01) and in EPX in BW (P < 0.01) and serum (P < 0.01) within the group receiving prednisolone. In the longitudinal study there was only a significant difference between ECP values associated with highest and lowest peak expiratory flow rate (PEFR) (P < 0.05). These data confirm a role for eosinophil activation in the airway in asthma pathogenesis, and add some support to the hypothesis that corticosteroids may inhibit eosinophil activation in asthma.

Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases

Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.

Synthesis of Interleukin-5 by Activated Eosinophils in Patients With Eosinophilic Heart Diseases

AbstractEosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (slL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and slL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.