Higher Levels Of Eosinophil Cationic Protein Research Articles

The benefit of dupilumab as a postoperative short-term adjuvant therapy for chronic rhinosinusitis with nasal polyps: A preliminary study.

Recent evidence recommends the use of biologics in patients with severe uncontrolled type 2 chronic rhinosinusitis with nasal polyp (CRSwNP) owing to its propensity for recurrence after functional endoscopic sinus surgery (FESS). Among the type 2 biologics used for the treatment of nasal polyps, dupilumab (Dupi, anti-IL-4) exhibited superior efficacy and safety in indirect comparison studies. This study aimed to evaluate the objective and subjective outcomes of patients with CRSwNP treated with and without adjuvant Dupi therapy after FESS. Adult patients with type 2 CRSwNP who underwent FESS with adjuvant Dupi after surgery were enrolled. A matched control group without adjuvant Dupi therapy were recruited during the same period. All patients underwent nasal endoscopy and completed the sinonasal outcome test-22 questionnaire evaluations at baseline and 3 months after surgery. A total of 10 patients who received postoperative adjuvant therapy with Dupi and 20 patients who underwent surgery only were included. Patients with add-on Dupi therapy had significantly higher eosinophil cationic protein levels in the serum, eosinophil counts in peripheral blood, prevalence of asthma, and nasal polyp score at baseline. Both treatments were effective in reducing the patient's symptoms by SNOT-22 at 3 months postoperatively. However, patients with adjuvant Dupi therapy exhibited significantly better endoscopic scores than those with surgery only (p = .022). Surgery plays an important role in treating patients with CRSwNP, and adjuvant Dupi use may facilitate objective mucosal recovery postoperatively. 4.

Activated Eosinophils Predict Longer Progression-Free Survival under Immune Checkpoint Inhibition in Melanoma.

Immune checkpoint inhibition (ICI) has yielded remarkable results in prolonging survival of metastatic melanoma patients but only a subset of individuals treated respond to therapy. Success of ICI treatment appears to depend on the number of tumor-infiltrating effector T-cells, which are known to be influenced by activated eosinophils. To verify the co-occurrence of activated eosinophils and T-cells in melanoma, immunofluorescence was performed in 285 primary or metastatic tumor tissue specimens from 118 patients. Moreover, eosinophil counts and activity markers such as eosinophil cationic protein (ECP) and eosinophil peroxidase (EPX) were measured in the serum before therapy start and before the 4th infusion of ICI in 45 metastatic unresected melanoma patients. We observed a positive correlation between increased tumor-infiltrating eosinophils and T-cells associated with delayed melanoma progression. High baseline levels of eosinophil count, serum ECP and EPX were linked to prolonged progression-free survival in metastatic melanoma. Our data provide first indications that activated eosinophils are related to the T-cell-inflamed tumor microenvironment and could be considered as potential future prognostic biomarkers in melanoma.

Blood eosinophil cationic protein and eosinophil-derived neurotoxin are associated with different asthma expression and evolution in adults

BackgroundEosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are proteins released by activated eosinophils whose role in adult asthma remains unclear.ObjectiveTo study associations between ECP, EDN and various asthma characteristics...

Serum eosinophil cationic protein: a prognostic factor for early postoperative recurrence of nasal polyps

The objective of this work was to assess the efficacy of serum eosinophil cationic protein (ECP) concentration in predicting early postoperative recurrence in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). We prospectively enrolled CRSwNP patients to receive bilateral functional endoscopic sinus surgery (FESS) and followed them for 1 year. Serum ECP level was measured within 1 week before surgery. Demographics and associated medical factors were analyzed with the surgical outcome, and nasal polyp histology was microscopically examined. Overall, 58 patients met the inclusion criteria and underwent FESS. After at least a 1-year follow-up period, 9 patients had postoperative recurrence, with significantly higher serum ECP levels (p = 0.030). Receiver operating characteristic curve analysis showed the optimal cutoff level of serum ECP concentration for predicting the postoperative recurrence of nasal polyps was 21.8 µg/L (p = 0.030). Regardless of atopy status and histology type, logistic regression analysis showed that a higher ECP level was the sole significant factor related to early postoperative recurrence of nasal polyps (odds ratio, 54.8; p = 0.014). Cox proportional hazard regression analysis revealed that the hazard ratio of CRSwNP patients with an ECP level of >21.8 µg/L resulting in early postoperative recurrence was 7.6 (p = 0.011). Serum ECP appears to be a feasible predictor for early postoperative recurrence of nasal polyps. CRSwNP patients with preoperative serum ECP levels of ≥21.8 µg/L had an approximately 55-fold increased risk of early recurrence. CRSwNP patients with higher preoperative serum ECP levels should be closely monitored within the first year after surgery.

Eosinophil-cationic protein - a novel liquid prognostic biomarker in melanoma

BackgroundThe role of eosinophils in cancer is not yet completely understood, but patients with eosinophilia show a trend towards longer survival in several types of cancer, including melanoma. However, eosinophil count at initial diagnosis of metastatic melanoma does not predict survival. Since eosinophil cationic protein (ECP) mediates anticancer effects, such as tissue remodelling and cytotoxic activity, we investigated this marker as an early prognostic marker in metastatic melanoma.MethodsSerum of 56 melanoma patients was collected at the time of diagnosis of metastatic disease. ECP levels as measured by ELISA were correlated with overall survival (OS) in patients before systemic therapy with immunotherapy or chemotherapy. Statistical analyses were performed using the Log–Rank (Mantel–Cox) test.ResultsThe median OS for patients with high serum ECP above 12.2 ng/ml was 12 months (n = 39), compared to 28 months for patients with ECP below this threshold (n = 17; p = 0.0642). In patients with cutaneous melanoma, excluding patients with uveal and mucosal melanoma, the survival difference was even more striking (p = 0.0393). ECP’s effect size on OS was observed independently of the consecutive therapy. ECP levels were not correlated with LDH levels.ConclusionECP seems to be a novel prognostic serum marker for the outcome of melanoma patients, which is independent of LDH and easy to perform in clinical practice. The striking negative prognostic value of high ECP level is unanticipated and can guide patient management.

Eosinophil-cationic protein: A novel liquid prognostic biomarker in melanoma.

e21573 Background: The prognostic role of eosinophils is still unclear with a trend towards longer survival for melanoma patients with eosinophilia at any point in their course of disease. However, eosinophil count at initial diagnosis of metastatic disease does not predict survival. Since eosinophil cationic protein (ECP) might mediate anticancer effects, such as tissue remodeling and cytotoxic activity, this marker was investigated as early prognostic marker preceding eosinophilia. Methods: Serum of 56 melanoma patients was collected at the time of diagnosis of metastatic disease. ECP levels as measured by ELISA were correlated with overall survival (OS) in patients before systemic therapy with immunotherapy or chemotherapy. Statistical analyses were performed using the Log–Rank (Mantel–Cox) test and Gehan-Breslow-Wilcoxon test. Results: The median OS for patients with high serum ECP above 10 ng/ml was 13 months, compared to 32 months for patients with ECP below this threshold (p = 0.0001). This striking survival difference was observed independently of the consecutive therapy. ECP levels were not correlated with LDH levels. Conclusions: ECP is a novel prognostic serum marker for predicting the outcome of melanoma patients which is independent of LDH and easy to perform in clinical practice. The negative prognostic value of high ECP level is unanticipated.

Association between inflammatory biomarkers and in-stent restenosis tissue features: an Optical Coherence Tomography Study

Inflammatory reaction after stent implantation is associated with in-stent restenosis (ISR). We assessed the association of optical coherence tomography (OCT) features of neointima with systemic levels of high-sensitivity C-reactive protein (hs-CRP) and eosinophil cationic protein (ECP) measured at the time of ISR detection. Patients presenting with symptomatic angiographically documented ISR (diameter stenosis ≥ 50% by visual estimation) were included. Quantitative OCT analysis included the measurement of minimal lumen diameter, minimal luminal area, stent and neointimal area, stent and restenosis length, restenotic tissue burden, and symmetry ratio. Qualitative OCT analysis included the assessment of ISR plaque type, neointimal tissue structure, lumen shape, presence of microvessels and calcific nodules. At the time of ISR detection hs-CRP and ECP levels were measured, and statistical analysis was performed using as cut-off 3 mg/L and 4.5 µg/L, respectively. Our population included 40 patients, 24 bare metal stents and 16 drug-eluting stents. Patients with high hs-CRP levels had a higher restenostic tissue symmetry ratio (0.56 ± 0.17 vs. 0.42 ± 0.13, P = 0.01) when compared with patients with low hs-CRP levels. Patients with high ECP levels had a higher neointimal burden (70 ± 14 vs. 64 ± 11, P = 0.05) in comparison with patients with low ECP levels. Inflammatory biomarkers assessed at the time of ISR detection are associated with different aspects of neointimal tissue. While hs-CRP seems to have a role in neointimal tissue shape, ECP is related to a neointimal burden.

Mediators and Cytokines in Persistent Allergic Rhinitis and Nonallergic Rhinitis with Eosinophilia Syndrome

Background: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. Methods: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. Results: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1β, IL-17, IFN-γ, TNF-α and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1β was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL- 5 was elevated in PAR only. Conclusions: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES.

Age-related differences in the pathogenesis of chronic rhinosinusitis

Age-related differences in the pathogenesis of chronic rhinosinusitis

Eosinophil Cationic Protein in Chronic Urticaria

Abstract Background: Eosinophil Cationic Protein (ECP) is a well-known activity indicator in allergic disease. Recently eosinophils have drawn attention as a major source of tissue factors in chronic urticaria. However, there have been few reports on significance of serum ECP in chronic urticaria. Aims: To evaluate the clinical significance of serum ECP in chronic urticaria and clarify the relationship between serum total IgE and ECP in a severity index. Methods: The retrospective chart review was performed on 114 patients with chronic urticaria. Serum ECP and total IgE were measured before treatment. The treatment period required to improve clinical symptoms with two different kinds of oral antihistamines twice a day was checked and the relationship between the treatment period and serum ECP and total IgE levels were evaluated. Results: Patients showing high ECP level before treatment need more time to manage their urticarial symptoms than those with low ECP level (p=0.018). However, there were no significant differences between treatment period and serum total IgE level (p=0.543). Serum ECP and total IgE was moderately correlated with each other (r=0.200, p=0.041). Conclusions: Serum ECP can be a better indicator of disease severity in chronic urticaria than IgE. The patients showing high ECP level from the beginning require relatively longer period for symptom relief and can be helped by more than two kinds of oral antihistamines.

Eosinophil Activation in the Cerebrospinal Fluid of Children with Shunt Obstruction

Objective: To determine if eosinophils are activated to release the cationic proteins, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) in shunt obstruction, and to find out if these proteins are associated with ventriculoperitoneal shunt failure. Patients and Methods: This was a prospective observational study carried out in a 20-bed tertiary pediatric intensive care unit. Patients studied were children aged 0–18 years with suspected ventriculoperitoneal shunt malfunction requiring shunt revision. No interventions were performed. Cerebrospinal fluid (CSF) was analyzed for cell count and EDN and ECP concentrations. Patients were prospectively followed for 6 months to evaluate shunt failure. Results: In a 2-month period, 56 shunt revisions were performed on 56 children. Three children had culture-proven infection. Eosinophilia, defined as ≧5% eosinophils in the CSF, was present in 9 out of 53 children (17%). The 3 patients with infection did not have eosinophilia and were excluded from further analysis. Patients with CSF eosinophilia had higher concentrations of ECP (1.38 ± 0.66 vs. 0.41 ± 0.15 ng/ml; p = 0.013) and EDN (16.94 ± 5.83 vs. 4.69 ± 1.33 ng/ml; p = 0.011). Patients with CSF eosinophilia did not have more ventriculoperitoneal shunt revisions within 6 months (6 of 9) compared to those who did not have eosinophilia (21 of 44; p = 0.50). However, patients with higher levels of ECP in the CSF required more shunt revisions within 6 months of their surgeries (p < 0.05). Conclusions: In patients with malfunctioning ventriculoperitoneal shunts, CSF eosinophils are activated and release ECP and EDN. The presence of ECP is associated with a shorter shunt life.

Clinical and Immunologic Effects of Sublingual Immunotherapy on Patients with Allergic Rhinitis to House-Dust Mites: 1-Year follow-up Results

There have been no data on sublingual immunotherapy (SLIT) in Asian patients with allergic rhinitis (AR) sensitized to house-dust mites (HDMs). This study aimed to investigate the efficacy and immunologic change after 12 months of SLIT in Korean patients. Fifty-eight patients, who had AR caused by Dermatophagoides pteronyssinus and Dermatophagoides farinae and who completed 12 months of SLIT were included. Symptom scores were evaluated before and after 12 months of SLIT, and medication scores were assessed throughout the study. Peripheral blood eosinophil counts, eosinophil cationic protein (ECP), total IgE, and specific IgE were also evaluated. All of the symptoms of AR were significantly improved with reduced medication scores. In addition, there were significant decrements in peripheral blood eosinophil counts and ECP (p = 0.025 and p = 0.048, respectively). Specific IgE for D. farinae slightly increased (p = 0.019), whereas specific IgE for D. pteronyssinus and total IgE did not change significantly. Thirty-six (62%) of 58 patients were in the effective response group. Although not statistically significant, findings in the study showed that the effective response group had a tendency to have higher ECP levels before SLIT than the ineffective response group (p = 0.056). SLIT improved the symptoms and medication scores in Korean patients with AR from HDM. Laboratory parameters including eosinophil counts, ECP, and specific IgE for D. farinae seemed to be modified after 1-year SLIT. A high ECP level may be a useful parameter to predict the effectiveness of SLIT and select the patient for the treatment.

Presence of Eosinophils in Nasal Secretion during Acute Respiratory Tract Infection in Young Children Predicts Subsequent Wheezing within Two Months

In young children with wheezing or bronchiolitis, especially with respiratory syncitial virus, blood eosinophilia and a high eosinophil cationic protein level in nasal secretions predicts subsequent wheezing in later childhood. However, whether eosinophil activation results from virus-induced inflammation or local eosinophilia per se precedes the onset of wheezing remains unknown. In the present study, we examined the association between the presence of nasal eosinophils during respiratory tract infection (RTI) and subsequent wheezing in young children. A total of 35 young children less than 3 years of age who visited our outpatient clinic with rhinorrhea between April and July 2004 were enrolled in this prospective cohort study. Subjects who were given diagnoses of allergic rhinitis were excluded. In all the subjects, the presence of eosinophils in nasal secretions was determined. The subjects were followed, and the cumulative incidences of wheezing during the subsequent 2- and 12-month periods were examined. According to a logistic regression analysis adjusted for age, sex, family history, allergies, and wheezing at entry, young children with nasal eosinophil infiltration during acute RTI had a significantly higher risk of wheezing during the subsequent 2 months, compared with those without nasal eosinophil infiltration (adjusted odds ratio, 27.618, p = 0.016). Our findings not only suggest that nasal eosinophil testing may serve as a convenient clinical marker for identifying young children at risk for subsequent wheezing, but also shed new light on the role of eosinophils in the onset of wheezing in young children.

Original article: Eosinophil cationic protein (ECP) polymorphisms and association with asthma, s‐ECP levels and related phenotypes

Background: Eosinophil cationic protein (ECP) is a potent cytotoxic secretory protein with bactericidal and antiviral properties. ECP is released by activated eosinophils and regarded as a marker of eosinophilic inflammation. High levels of ECP have been reported in cases of active asthma and other allergic diseases. This study aimed to assess whether three single‐nucleotide polymorphisms (SNPs) in the ECP gene (RNASE3) on chromosome 14 q24–q31 or their haplotypes are associated with asthma, allergy, or related phenotypes.Methods: The three SNPs −38CA, +371CG and +499CG in RNASE3 and their haplotypes were analyzed for associations with asthma, serum‐ECP (s‐ECP) levels, allergic sensitization (positive skin‐prick test to common allergens), bronchial hyperresponsiveness (BHR) assessed by methacholine inhalation, and serum‐IgE (s‐IgE) levels in 177 families from Norway and the Netherlands identified through siblings with asthma.Results: Transmission disequilibrium test (TDT) demonstrated significant associations between the A‐G‐G haplotype and asthma as well as the specific phenotypes allergic asthma (but not non‐allergic asthma), high s‐ECP, high s‐IgE and BHR, while the C‐G‐G haplotype was associated with reduced occurrence of these traits. In addition, the −38A allele was associated with high s‐ECP levels and allergic asthma.Conclusion: The present study suggests that the A‐G‐G haplotype in the RNASE3 gene influences the development of asthma, in particular, an allergic form of asthma. Furthermore, as the −38CA SNP lies in close vicinity of known intron‐regulatory sites, results of SNP analysis suggest that the detected association is possibly linked to a genetic transcriptional control of s‐ECP levels.

Serum Clara Cell Protein as an Indicator of Pulmonary Impairment in Occupational Exposure at Aluminum Foundry

Although some of the exposures in aluminum (Al) smelting have been well characterized, and respiratory disorders in aluminum production workers are well known, the relationship between internal aluminum loads and appropriate lung biomarkers have not been elucidated. The aim of our work was to carry out a comprehensive investigation in workers employed in the Aluminum Foundry Casting Department with special reference to currently existing hygiene standards, known as threshold limit values (TLV) based on aluminum effects on the respiratory system. The measurement of serum anti-inflammatory Clara cell protein (CC16) was employed as a peripheral marker of the lung epithelium function. A group of 50 casting smelters, 5 locksmiths, 11 sawyers and auxiliary workers exposed to dust containing 14% of aluminum, and a group of 42 controls were examined. Respiratory function tests were performed and forced volume capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory volume in the first percent (FEV1%), forced expiratory flows in 50% VC (FEV50), and markers of foundry workers' exposure and body burden, Al concentration in the breathing zone, blood and urine, biomarkers of the effects of exposure, concentration of CC16 and hyaluronic acid (HA) in serum were determined in all examined workers. Additional measurements comprised determinations of serum iron (Fe) levels, myeloperoxidase (MPO), eosinophil cationic protein (ECP), immunoglobulin E (IgE), glutathione S-transferase (GST), and superoxide dismutase (SOD) activity in erythrocytes. The group of casting smelters was characterized by the highest levels of aluminum in urine (Al-U) (43.7 microg L(-1)), high levels of MPO, ECP and IgE, high SOD activity, low CC16 levels, and low activity of GST. Lower Al-U excretion was observed in locksmiths (35.2 microg L(-1)) and sawyers (21.7 microg L(-1)). Serum CC16 proved to be the most sensitive biomarker, showing high inverse relationship with serum Al (Al-S) concentrations in casting smelters (p = 0.006). The study showed that in conditions of occupational exposure, dusts containing Al2O3 < 1 mg m(-3) cause changes in the respiratory system and biomarkers in serum, especially in CC16, connected with altered functioning of this system. Changes in concentrations of the examined biomarkers and also in respiratory parameters of the study subjects were observed when Al-U concentration was > 40 microg L (-1).

Markers of eosinophil activation in fasting gastric juice in infants with wheezing episodes

Rationale Children with wheezing during early childhood represent different subgroups with regard to pathophysiology and prognosis. Transient wheezing does not need early treatment whereas persistent wheezing especially with atopy has a high risk of subsequent asthma, making early recognition important, although there is no reliable predictor of asthma. In this study we examined eosinophils and eosinophil cationic protein (ECP), in order to find a reliable and practical laboratory marker for forthcoming clinical characteristics of asthma in infants with wheezy bronchitis. Methods The study group consisted of thirty infants (19 boys and 11 girls), mean age 1.3 ± 0.8 (min:0.2, max:3) years, who were coming with acute episode of wheezing attacks. They were divided into two groups; Group 1: with only one or two episodes, and Group 2: with three or more episodes. Important demographic data and history of personal and family atopy, peripheral eosinophilia, serum ECP level, ECP in fasting gastric juice, total IgE were recorded for each child and compared between the groups. Results There were no difference in serum ECP levels, peripheral and gastric juice eosinophilia between the two groups. However, mean level of gastric juice ECP was 78.24 ± 86.57 u/gl for Group 1, and 148.87 ± 83.57 u/gl for Group 2, and the difference between the groups were statistically significant (p=0.027). Conclusion Gastric juice ECP level was the only parameter significantly higher in group with three and more wheezing attacks. We conclude that high levels of gastric juice ECP may be an important marker for subsequent wheezing attacks.

Nitric Oxide Metabolites, Eosinophils and Eosinophilic Cationic Protein in Patients with Asthma: Sputum versus Blood

The monitoring of airway inflammation has assessed in bronchial asthma directly by sputum examination, and indirectly by measurements in peripheral blood. To investigate the diagnostic value of these two methods, we compared nitric oxide (NO) metabolites, eosinophils, and eosinophil cationic protein (ECP) in sputum and blood in patients with asthma and control subjects. Sputum and serum were obtained from fifteen patients with asthma, and then were examined before anti-asthma treatment, including steroid preparations. ECP was measured by fluoroimmunoassay. NO metabolites were assayed by using modified Griess reaction. Asthmatic patients, compared with control subjects, had significantly higher level of NO metabolites, higher proportion of eosinophils, and higher levels of ECP in sputum. Asthmatic patients, compared with control subjects, however, had significantly higher number of eosinophils, and were at higher levels of ECP in blood. FEV1, FEV1/FVC was negatively correlated with sputum eosinophils. The area under receiver operating characteristic (ROC) curve showed that eosinophils in sputum are significantly accurate markers than NO metabolites in sputum and blood. These findings suggest that the proportion of eosinophils in sputum have more accurate diagnostic marker of asthmatic airway inflammation than NO metabolites in sputum in differentiating asthmatic patients from control subjects.

Measurement of Inflammatory Mediators of Eosinophils and Lymphocytes in Blood in Acute Asthma: Serum Levels of ECP Influence the Bronchodilator Response

The aim of this study was to assess the relevance of immunoinflammatory markers on the response to short acting β₂-agonist in acute asthma exacerbation. Thus, we measured serum eosinophil cationic protein (ECP) levels and sIL-2R at acute exacerbation in 52 adult patients with atopic asthma, and assessed forced expiratory volume in 1 s (FEV₁) before and after the administration of aerosolized salbutamol. After a cumulative dose of salbutamol causing a 10% improvement in FEV₁ from baseline [CD10, i.e. cumulative doses of salbutamol (800 µg) causing an improvement in FEV₁ from baseline to 10%] the patients were divided into two groups: group A with CD <10 and group B with CD >10. The bronchodilator response, as defined by a ΔFEV₁ (percentage of predictive value of FEV₁) of ≧10 predictive value, was shown by 40% of the patients. After 200, 400 and 800 µg of salbutamol, significant differences of FEV₁ with respect to baseline values were, respectively, p = 0.049, 0.0039 and 0.0014. In contrast, no significant difference of the means of FEV₁ between the doses of salbutamol was observed. Significant differences of ΔFEV₁ between 200 and 400 µg (p = 0.0002) and between 200 and 800 µg (p < 0.0001) were observed, but not between 400 and 800 µg of salbutamol. There were significant correlations between baseline values of predictive FEV₁ and serum ECP levels (rho = –0.60, p < 0.0001) and sIL-2R levels (rho = –0.35, p = 0.01) respectively. Besides, a correlation between ΔFEV₁ and serum ECP levels (rho = –0.53, p < 0.0001) was observed, whereas no correlation was found between ΔFEV₁ and sIL-2R. By analyzing differences between the two groups (A and B) for serum ECP levels, sIL-2R and blood eosinophil count, a significant difference was found for serum ECP levels. We conclude that subjects with acute exacerbation of asthma show high serum levels of ECP and sIL-2R and, more interestingly, that the response to brochodilator was higher in patients with lower serum ECP levels.

Analysis of sputum taken from wheezy and asthmatic infants and children, with special reference to respiratory infections

Children who are destined to develop asthma are considered to be susceptible to a variety of respiratory pathogens. To elucidate respiratory inflammation among these children, we measured the levels of eosinophil cationic protein (ECP) and tryptase in sputum taken from three different groups of wheezy infants and young children: those with a first wheeze (n = 15); those with recurrent wheeze (n = 27); and those with recurrent wheeze with respiratory distress, namely asthma (n = 56). The numbers of eosinophils or metachromatic cells determined by microscopic analysis of sputum samples were also evaluated in combination with the ECP and tryptase levels. Although neither sputum ECP nor tryptase was a clear discriminative marker that differentiated the three different types of wheezy disease, ECP levels in sputum from the asthma group were significantly higher (2,269.2 +/- 6,216.8 ng/g) than those in the recurrent wheezy group (440.3 +/- 1,199.8 ng/g) or in the first-wheeze group (209.0 +/- 172.9 ng/g). A similar trend was observed with tryptase levels in sputum, but there were no significant differences among the three groups. Sputum taken from asthmatic children showed a marked accumulation of eosinophils. However, an accumulation of eosinophils in sputum (even in the presence of an elevated level of sputum ECP) was not identified in the asthmatic infants < 1 year of age. An accumlation of eosinophils in sputum was not evident until children became > 1 year old and thereafter the eosinophils rapidly increased in number until the children reached 5 years of age. It was noteworthy that sputa positive for pathogenic bacteria, taken from the 1- and 2-year-old asthmatic infants, had a tendency to show high levels of ECP but a reduced number of eosinophils. Along with the wheezy episodes induced by viral infection, primarily and occasionally in combination with secondary bacterial infection, eosinophil activation and infiltration may develop. These predestined immune reactions to various pathogens might be associated with triggering the onset of asthma.

Eosinophil cationic protein relates to sputum neutrophil counts in healthy subjects

Eosinophil cationic protein (ECP) has been regarded as an eosinophil-specific protein. Sputum ECP levels have been shown to be elevated (median [interquartile range (IQR)], 1040 [3008] μg/L) in stable asthmatic subjects with sputum eosinophilia (median [IQR], 5.2% [19.4%] eosinophils).1 However, it has recently been shown that proteins immunochemically indistinguishable from ECP are also present in peripheral blood neutrophils.2 High levels of sputum ECP have also been observed in subjects without associated sputum eosinophilia.