Eosinophil Cationic Protein Concentrations Research Articles

Performance of Eosinophil Cationic Protein as a Biomarker in Asthmatic Children

Although blood eosinophils are a frequently used marker of type 2 inflammation in children with asthma, their sensitivity is relatively poor. Additional markers of type 2 inflammation are needed. We hypothesized that plasma concentrations of eosinophil cationic protein (ECP), a marker of eosinophil activation, would be useful for detection of type 2 inflammation and would predict poorer asthma outcomes over 1 year. Children and adolescents 6 through 17 years (N= 256) with confirmed asthma completed a baseline visit and a follow-up visit at 12 months. A subsetalso underwent systemic corticosteroid responsiveness testing with intramuscular triamcinolone. Outcome measures at 12 months included uncontrolled asthma, lung function, and asthma exacerbations treated with systemic corticosteroids. Plasma ECP concentrations ranged from 0.03 to 413.61 ng/mL (median, 6.95 ng/mL) and were consistently associated with other markers of type 2 inflammation. At baseline, children in the highest ECP tertile had poorer asthma control, more airflow limitation, and more exacerbations, but also had greater symptom improvement with intramuscular triamcinolone. At 12 months, associations between the highest ECP tertile and exacerbations, but not lung function or asthma control, persisted after covariate adjustment. However, the sensitivity of ECP was modest and was not markedly different from that of blood eosinophil counts. Plasma ECP concentrations may be a useful marker of type 2 inflammation in children and may help identify those children at highest risk for recurrent exacerbations who could benefit from corticosteroid treatment. However, additional markers may be needed to improve sensitivity for outcome detection.

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.

Study of eosinophil cationic protein serum levels in patients with toxocariasis

Introduction: Toxocariasis is a zoonotic helminth infection with difficult diagnosis. Determination of specific IgG antibodies alone does not allow to establish the disease stage and to evaluate the treatment efficacy. Therefore it is necessary to identify additional markers that will assist the diagnosis. The purpose of our study was to identify and monitor eosinophil cationic protein (ECP) levels in patients with toxocariasis confirmed by serology and to compare our data with the literature to determine the relevance of this protein as an indicator for recent infection and the effectiveness of the therapy. Material and methods: ELISA (CUSABIO) commercial kit was used for determination of ECP concentration. Sixty serum samples were studied from individuals previously tested and confirmed for toxocariasis by the presence of specific anti-Toxocara IgG antibodies in ELISA (Toxocara IgG Rbiopharm) and the presence of specific bands in Western blot as confirmatory test (LD BIO). Twenty serum samples from clinically healthy blood donors were used as a control group. Results: The mean concentration of serum ECP in the patients with toxocariasis was significantly higher than in clinically healthy subjects. Seventy-two percent of patients affected by toxicariasis showed increased serum concentration of ECP. However, no statistically significant differences were observed in terms of age (p = 0.451) and sex (p = 0.682) of the patients or clinical form of the disease. ECP levels among patients with visceral toxocariasis were relatively higher (mean 22.99 ng / ml ± 13.16 SD) in comparison to those with ocular involvement (15.60 ng/ml ± 9.92 SD). Correlation between the presence of peripheral eosinophilia and the concentration of serum ECP was not also established. Conclusion: Data from our study give us reason to believe that serum levels of ECP could serve as an additional marker indicating recent infection, especially in patients without marked increase in the blood eosinophils.

Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease

Background: Non-invasive markers for predicting relapse would be a useful tool for the management of patients with inflammatory bowel disease. Eosinophil granulocytes and their granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) have previously been shown to reflect disease activity in Crohn’s disease and ulcerative colitis.Aim: To examine the capacity of faecal ECP and EDN to predict relapse in ulcerative colitis and Crohn's disease, and to compare these proteins with faecal calprotectin.Methods: Patients with Crohn's disease (n = 49) and ulcerative colitis (n = 55) were followed prospectively until relapse or end of the two-year study period. Faecal samples were obtained every third month. The predictive value of ECP and EDN was assessed in Cox regression models.Results: In ulcerative colitis, a doubled EDN or ECP concentration was associated with a 31% and 27% increased risk of relapse, respectively. EDN levels were increased both at relapse and three months prior. By contrast, in Crohn's disease, the concentration of EDN was higher among patients in remission than in those who relapsed. Correlations between faecal calprotectin, ECP and EDN were observed in both diseases.Conclusions: We demonstrate that the risk of relapse in ulcerative colitis can be predicted by consecutively measuring faecal EDN every third month, and suggest EDN as a complementary faecal marker to calprotectin to predict future relapse in ulcerative colitis. Our finding of higher EDN in Crohn’s disease-patients staying in remission than in those who relapsed indicates different functions of the protein in ulcerative colitis and Crohn’s disease.

ЕФЕКТИВНІСТЬ ЕЛІМІНАЦІЙНОЇ ДІЄТИ У ДІТЕЙ ГРУДНОГО ВІКУ З ГАСТРОІНТЕСТИНАЛЬНИМИ ПРОЯВАМИ ХАРЧОВОЇ АЛЕРГІЇ


 
 
 The purpose of the work was to evaluate the effectiveness of the elimination diet in infants with gastrointestinal manifestations of food allergy.Patients and methods. 84 children aged 2 months to 1 year were examined with gastrointestinal food allergy to cow's milk proteins. All children were prescribed an elimination diet with the exclusion of cow's milk proteins. An assessment was made of the regression of gastrointestinal symptoms on day 3, 7 and 14 of diet therapy and the determination of the concentration of eosinophilic cationic protein in serum. The general-clinical, immunological, allergological and statistical methods of research were used.Results. The purpose of the elimination diet with the exclusion of cow's milk proteins for nursing mothers and the use of mixtures with extensive hydrolysis of protein in the case of artificial feeding leads to a complete regression of gastrointestinal and skin symptoms in all examined children on the 14th day of diet therapy, which is further confirmed by the normalization of the concentration of eosinophilic cationic serum protein in diet therapy. Conclusions. Elimination of cow's milk proteins in infants with gastrointestinal food allergy results in complete regression of gastrointestinal and skin symptoms on day 14 of diet therapy, and determination of the concentration of eosinophilic cationic protein in serum can be used as an additional criterion for the effectiveness of diet therapy.
 
 

The Clinicopathological Profile of Eosinophilic Myocarditis.

Eosinophilic myocarditis (EM) is a rare form of myocarditis. As there is extreme diversity in its manifestations, the true incidence is difficult to assess and no proper epidemiological criteria are present. It generally presents with a wide array of clinical manifestations. Clinical presentation tends to differ in cases and not all the patients show the same signs and symptoms. The etiology of EM often remains obscure but potential causes have been identified which may include hypersensitivity to drugs, exposure to certain viruses and parasites, and hyper-eosinophilic syndromes. Endomyocardial biopsy is considered to be a gold standard for the diagnosis of EM. Echocardiography, cardiac magnetic resonance, and bio markers particularly serum eosinophilic cationic protein concentrations are also known to aid in diagnosis. EM may lead to progressive, irreversible, and fatal myocardial damage if prompt diagnosis is not made and therapy is not initiated. The current treatment regimens include corticosteroids, cytotoxic agents, and immunosuppressive therapy. However, a proper treatment criterion is yet to be established.

Eosinophil Cationic Protein Concentrations among Crop and Dairy Farmers with Asthma.

OBJECTIVE:To assess the mean serum eosinophil cationic protein (s-ECP) concentrations among crop and dairy farmers and office controls, and further examine its relation to exposure duration, smoking habit, as well as presence or absence of asthma.METHODS:A cross-sectional survey was performed including examined group (EG), composed by agricultural workers (87 crop - EG1 and 83 dairy farmers - EG2), and control group (CG) composed by 80 office workers within the same enterprise. We have used a questionnaire to record the chronic respiratory symptoms, detailed work history, specific farming activities and tasks performed and smoking history. Evaluation of examined subjects also included lung function tests, diagnosis of asthma, and measurement of s-ECP as a marker of inflammation.RESULTS:The main finding of the present study is that s-ECP concentrations were raised in subjects with asthma independent of the smoking habit. The mean s-ECP concentrations were higher in subjects of EG1 and EG2 compared with those in CG, but without reaching statistical significance. Mean s-ECP concentrations were significantly higher among subjects in EG1 exposed more than 20 years, while mean s-ECP concentrations were non-significantly higher in subjects of EG2 exposed more than 20 years, compared to those exposed less than 20 years. Mean s-ECP concentrations were higher among smokers within all three groups, but without reaching statistical significance between smokers and non-smokers. Mean s-ECP concentrations were significantly higher in subjects with asthma within EG1 (P = 0.049) and EG2 (P = 0.040), but also within those in CG (P = 0.046).CONCLUSION:Data obtained suggest that airway inflammation is present in farmers with asthma, and s-ECP is an important biomarker in means of reflecting disease severity and prognosis among exposed workers.

Serum eosinophil cationic protein concentrations do not predict response to anti-interleukin 5 antibody treatment in patients with severe uncontrolled eosinophilic asthma

Serum eosinophil cationic protein (ECP) has been described as a marker reflecting the degree of activation of eosinophils in asthma, therefore indirectly measuring the degree of airway inflammation.

Effect of Xiaochuanping powder on the inflammatory response and airway remodeling in asthmatic rats

OBJECTIVETo observe the effect of Xiaochuanping powder (XP), a traditional Chinese prescription for the treatment of cough and asthma, on serum concentrations of eosinophil cationic protein (ECP), tumor necrosis factor (TNF)-α, and interleukin (IL)-4, eosinophil counts, as well as expression of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 in the lung tissues of asthmatic rats. METHODSSixty clean-grade Sprague–Dawley rats were divided randomly into six groups: normal control (NC), asthma model, Guilong Kechuanning (GK) group, as well as high-, intermediate-, and low-dose XP groups. Rats were sensitized with ovalbumin (OVA) to trigger asthma. Serum concentrations of ECP, TNF-α and IL-4, eosinophil counts, as well as expression of MMP-9 and TIMP-1 in lung tissues were evaluated using an immunofluorescence method. mRNA expression of MMP-9 and TIMP-1 was determined using real-time quantitative polymerase chain reaction. RESULTSCompared with the asthma-model group, serum concentrations of ECP, TNF-α, and IL-4, and eosinophil counts decreased significantly in the high- and intermediate-dose XP groups and GK group (all P < 0.01). Protein expression of MMP-9 and TIMP-1 decreased significantly in the high- and intermediate-dose XP groups and GK group (all P < 0.01). Transcription of MMP-9 and TIMP-1 mRNA and the ratio of expression of MMP-9: TIMP-1 in lung tissue were significantly lower (P < 0.01). CONCLUSIONXP can reduce TNF-α secretion, suppress the infiltration / activation of eosinophils, reduce serum concentrations of ECP and IL-4, reduce the protein and mRNA expression of MMP-9 and TIMP-1 in lung tissue, and regulate the balance between expression of MMP-9 and TIMP-1. In these ways, XP alleviated the inflammation and remodeling of the airways.

Functional magnetic nanoparticles–assisted electrochemical biosensor for eosinophil cationic protein in cell culture

A low-cost electrochemical biosensor, assisted by a new type of functional magnetic nanoparticles (NPs), has been developed to detect eosinophil cationic protein (ECP), a known biomarker of asthma, in cell culture. The heparin-modified magnetic NPs were mixed with a sample solution containing ECP. After ECP had been captured by the NPs, a magnetic field was applied behind a graphite-based screen-printed electrode. The functional magnetic NPs were attracted to the electrode, raising the ECP concentration near its surface. Because of the use of the functional magnetic NPs, the difference in the signal was amplified when applying larger sample volumes for detection, thereby enhancing the sensitivity of the biosensor. This approach provided a linear range for the analysis of the logarithm of the ECP concentration from 1 to 1000nM, with a coefficient of determination 0.992; the limit of detection was 0.30nM. The fabricated biosensor displayed good recovery in a cell culture medium incubated with the Beas–2B cell line. The ability to detect the concentration of ECP in a cell culture at any time point should be useful for explaining contradictory findings regarding the relationship between the initial ECP concentration and the cell line.

Eosinophilic biomarkers for detection of acute exacerbation of chronic obstructive pulmonary disease with or without pulmonary embolism.

Eosinophilia has been implicated in the pathophysiology of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the role of eosinophil activation in the development of AECOPD remains unclear. In the present study, the reliability of plasma levels of eosinophil activation markers, including eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPX), were measured and used as diagnostic biomarkers of AECOPD with or without pulmonary embolism (PE). A total of 47 patients with AECOPD, 30 patients with AECOPD/PE and 35 healthy adults were enrolled in the present study. Plasma levels of ECP, EDN, EPX and MBP were measured using commercial ELISA kits. The mean concentrations of plasma ECP, EDN, EPX and MBP in the patients with AECOPD was significantly 2.87-, 3.06-, 1.60- and 1.92-fold higher, respectively, compared with the control group (P<0.05). Similar results were obtained in patients with AECOPD/PE, for whom plasma levels of ECP, EDN, EPX and MBP were significantly 2.06-, 2.21-, 1.42- and 2.42-fold higher, respectively, compared with the controls (P<0.05). No significant differences were observed in the levels of these proteins between patients with AECOPD or AECOPD/PE. Among the four potential markers, ECP was determined to be the optimal marker for distinguishing patients with AECOPD or AECOPD/PE from the controls. No significant correlation was observed between marker concentrations and gender, age or disease severity. The results of the present study may have clinical applications in the diagnosis of AECOPD using these novel biomarkers.

Eosinophil Cationic Protein (ECP), a predictive marker of bullous pemphigoid severity and outcome

Bullous Pemphigoid (BP) is an inflammatory rare autoimmune bullous dermatosis, which outcome cannot be predicted through clinical investigations. Eosinophils are the main immune infiltrated cells in BP. However, the release of Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN), and Eosinophil Cationic Protein (ECP) upon eosinophil activation has still not been evaluated with respect to BP development. MBP, EDN and ECP were measured by ELISA in serum (n = 61) and blister fluid (n = 20) of patients with BP at baseline, and in serum after 2 months of treatment (n = 41). Eosinophil activation in BP patients was illustrated at baseline by significantly higher MBP, EDN and ECP serum concentrations as compared with control subjects (n = 20), but without distinction according to disease severity or outcome. EDN and ECP values were even higher in the blister fluids (P < 0.01 and P < 0.05, respectively), whereas MBP values were lower (P < 0.001). ECP serum concentration decreased after 60 days of treatment in BP patients with ongoing remission but not in patients who later relapsed (P < 0.05). A reduction of at least 12.8 ng/mL in ECP concentrations provided a positive predictive value for remission of 81%, showing that ECP serum variation could be a useful biomarker stratifying BP patients at risk of relapse.

Inhaled corticosteroid dose response in asthma: Should we measure inflammation?

BackgroundInhaled corticosteroid (ICS) titration in asthma is primarily based on symptoms and pulmonary function. ICSs may not be increased on this basis despite residual airway inflammation. ObjectiveTo compare the dose-response relationships of ICSs on measures of pulmonary function, symptoms, and inflammation in patients with persistent asthma. MethodsWe performed a pooled post hoc analysis of 121 patients with mild to moderate asthma from 4 randomized clinical trials that incorporated an ICS dose ramp. Dose ramps were 0 to 200, 0 to 800, and 200 to 800 μg/d (beclomethasone equivalents). Outcome measures included spirometry, fractional exhaled nitric oxide, airway hyperresponsiveness (AHR), symptoms, serum eosinophilic cationic protein, and blood eosinophils. ResultsWe found a plateau beyond a small improvement at 0 to 200 μg for forced expiratory volume in 1 second: 3.3% (95% confidence interval [CI], 2.0%–4.7%) at 0 to 200 μg vs 0.3% (95% CI, −0.8% to 1.4%) 200 to 800 μg (P = .001). A similar plateau was seen for symptom improvement beyond 0 to 200 μg. Inflammatory and AHR outcomes revealed further room for improvement beyond low-dose ICSs. There was dose-related suppression (P < .001) for fractional exhaled nitric oxide: 40.4 ppb (95% CI, 34.7–46.9 ppb) for ICS free, 26.8 ppb (95% CI, 23.4–30.2 ppb) for 200 μg, and 20.8 ppb (95% CI, 18.8–23.1 ppb) for 800 μg. Eosinophilic cationic protein concentration was significantly reduced with both higher dose ramps. Eosinophil counts also improved across all 3 dose ramps, with dose separation of 370/μL (95% CI, 280–450/μL) for ICS free vs 250/μL (95% CI, 200–300/μL) 800 μg (P = .03). AHR improved with all 3 dose ramps, with greater improvement at lower doses for indirect vs direct challenges. ConclusionICS dose response may extend beyond low dose for inflammation and AHR but not symptoms or spirometry. Further study is required to identify whether this correlates with suboptimal longitudinal asthma control. Trial RegistrationClinicalTrials.gov Identifiers: NCT00667992, NCT00995657, NCT01216579, NCT01544634.

Association Between Sensitization to Mold and Impaired Pulmonary Function in Children With Asthma.

PurposeRecent data indicate that sensitization to mold contributes to the severity and persistence of asthma. In this study, we investigated the relationships between sensitization to mold and lung function parameters in children with asthma.MethodsWe retrospectively reviewed clinical data from 551 asthmatic subjects. We selected subjects who met clinical diagnostic criteria of asthma. Their spirometry, methacholine challenge tests, and measurements of blood eosinophils, serum IgE, eosinophil cationic protein (ECP) and fractional exhaled nitric oxide (FeNO) results were included. Skin prick testing (SPT) results with 13 common aeroallergens in Korea including house dust mites, animal dander, pollen, cockroach and mold were reviewed. Subjects were divided into 3 groups according to their SPT results. Subjects who showed no positive result to any aeroallergen were designated as group 1 (non-sensitized). Group 2 represented subjects who were sensitized to aeroallergens other than mold (other allergen-sensitized) and group 3 included subjects who were sensitized to mold allergens (mold-sensitized).ResultsAmong the 551 asthmatic subjects, 67 (12.2%) were sensitized to mold and 366 (66.4%) were sensitized to other aeroallergens. The log mean IgE levels were higher in groups 2 (5.96±1.14 IU/mL) and 3 (5.81±0.97 IU/mL) compared to group 1 (3.88±1.68 IU/mL). Blood eosinophils, ECP and FeNO concentrations were significantly higher in groups 2 and 3, but no significant difference was found between the 2 groups. The mean FEV1 value was significantly lower in group 3 (86.9±12.1%pred) than in groups 2 (92.0±14.8%pred) and 1 (93.4±15.4%pred). The log mean methacholine PC20 was significantly lower in group 3 (0.08±1.91 mg/mL) than in groups 2 (1.31±1.69 mg/mL) and 1 (2.29±1.66 mg/mL).ConclusionsWe observed a differential association between mold and other aeroallergen sensitization, and severity of asthma. Sensitization to mold is associated with lower lung function and increased airway hyper-responsiveness in children with asthma. Mold sensitization could be an important factor determining asthma severity particularly airflow limitation in children.

Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois

CRSsNP is a heterogenous disease but type 2 inflammation in CRSsNP was more common than type 1 inflammation among patients in Chicago, Illinois. Distinct therapeutic strategies may be needed depending on the type of inflammation found in CRSsNP.

The significance and application of serum eosinophil cationic proteinand IgG4 antibody in patients with allergic rhinitistreated by allergic specific immunotherapy

Objective:To study the significance and application of serum eosinophil cationic protein(ECP) and IgG4 antibody in patients with allergic rhinitis treated by allergic specific immunotherapy.Method:The level of IgG4 antibody and eosinophil cationic protein in serum was measured in 33 cases of allergic rhinitis before treatment and half a year and one year after treatment.The change of ECP level was observed in different age groups,and the relationship between serum IgG4 and ECP after treatment was analyzed.Result:IgG4 antibody in the serum significantly increased after treatment,and the difference was statistically significant(P<0.05).In the serum ECP content gradually reduced after treatment,and the difference was statistically significant(P<0.05).No obvious difference in ECP level was observed among dfferent age groups after treatment (P<0.05).The level of serum IgG4 was negatively correlated with serum ECP level despite statistical insignificance(r=-0.138,P>0.05).Conclusion:ECP is a sign of eosinophil activation,which is an important factor leading to the nasal inflammation.The content of serum ECP can be used as an indicator for patients with allergic rhinitis recieving nonspecific immune treatment .IgG4 antibody is a relatively reliable indicator to evaluate the treatment effect of specific immunotherapy,and may be negatively related to the serum ECP levels.

Association of serum eosinophilia and total immunoglobulin E concentration with the risk of allergic symptoms and allergic sensitization, respectively: A 2-year follow-up study

ObjectivesSerum eosinophil percentage (SEP), eosinophil cationic protein (ECP) concentration, and total IgE (TIgE) concentration are known to increase in patients with allergic disease; however, the relevance of these elevated markers in children with negative allergic test results remains unclear. Therefore, this 2-year follow-up study aimed to investigate whether SEP, ECP concentration, and TIgE concentration are associated with an increased risk for allergic sensitization and allergic symptoms. MethodsIn 2012, SEP, ECP concentration, and TIgE concentration of third- and fourth-grade students from 6 elementary schools were measured. Skin prick test was performed, and the presence of allergic nasal symptoms was investigated using a questionnaire. In 2014, the same examinations were performed in the same set of students, who were then in the fifth and sixth grades, respectively, of the same schools. The cut-off value and usefulness of serologic markers (eosinophil count, ECP concentration, and TIgE concentration) were calculated using the receiver operating characteristic curve. ResultsSerum eosinophil percentage (cut-off value, 3.8%) was associated with the newly developed allergic nasal symptoms (sensitivity, 77.9; specificity, 41.8). A high serum TIgE concentration (cut-off value, 17.7 IU/mL) was also associated with the risk for allergic sensitization (sensitivity, 46.3; specificity, 85.3). ConclusionSEP and TIgE concentration were associated with the development of allergic symptoms and allergic sensitization, respectively, 2 years after the first examination.

The impact of passive smoking on asthma control in children

Objectives: To determine whether passive smoking affects spirometry parameters and allergy blood test results in children; to verify if there is a difference in spirometry parameters and allergy blood test results in children whose household members smoke within the household and children whose household members smoke outside the household; to verify if there is a difference in spirometry parameters and allergy blood test results in children in regard to the number of smokers in the household; to determine if there is a connection between tobacco smoke and the number of allergens in children; to determine if the number of daily smoked cigarettes inside the household correlates with the spirometry parameters and allergy blood test results in children. Design: A retrospective cohort study was conducted. Settings: The study was conducted in the allergy clinic of the Children's ward of the Clinical Medical Centre Split. Patients and methods: The study included 60 children, aged between 5 and 18 with a diagnosis of asthma, who were brought in the allergy clinic by their parents. Children were divided into two groups: a group of 36 children whose household members smoke and a group of 24 children whose household members do not smoke. We analyzed: spirometric parameters (PEF, FVC, FEV1, FEF25, FEF50, FEF75) before and after (VENT_FEF50, VENT_FEF75) we performed a bronchodilatator test with two salbutamol 100 micrograms/dose inhalations; allergy blood tests (Dunger test, relative eosinophile count, concentration of eosinophil cationic protein (ECP), total serum IgE concentration) and eosinophile count in the nasal swab. All the necessary data was gathered from the questionnaire filled out by the parents and by accessing the patients' medical history on the computer. Results: There is no statistically significant difference in spirometry parameters (PEF, FVC, FEV1, FEF25, FEF50, FEF75, VENT_FEF50, VENT_FEF75), eosinophile count in the nasal swab and allergy blood tests (Dunger test, relative eosinophile count, concentration of eosinophil cationic protein (ECP), total serum IgE concentration) between the group of children whose household members smoke and whose household members do not smoke. ECP concentration has shown a statistically significant difference between the group of children whose household members smoke within the household and the group of children whose household members smoke outside the household (P = 0,009). The number of daily smoked cigarettes inside the household statistically significantly correlates with relative eosinophile count in children (P = 0,048). There is no statistically significant difference in spirometry parameters (PEF, FVC, FEV1, FEF25, FEF50, FEF75, VENT_FEF50, VENT_FEF75), eosinophile count in the nasal swab and allergy blood tests (Dunger test, relative eosinophile count, concentration of eosinophil cationic protein (ECP), total serum IgE concentration) between the groups of children in regard to the number of smokers in the household. There is no statistically significant connection between the smoking of the household members and the number of allergens in children. Conclusion: Even though most of the published papers have proven that passive smoking has an effect on development of childhood asthma, this research did not find statistically significant difference in spirometry parameters (PEF, FVC, FEV1, FEF25, FEF50, FEF75, VENT_FEF50, VENT_FEF75), eosinophile count in the nasal swab and allergy blood tests (Dunger test, relative eosinophile count, concentration of eosinophil cationic protein (ECP), total serum IgE concentration) between the groups of children whose household members smoke and children whose household members do not smoke. The number of smokers in the household also did not show significant effect on the aforementioned values. We did not find a connection between passive smoking and the number of allergens in children. A statistically significant difference was found in the ECP value between the group of children whose household members smoke within the household and the group whose household members smoke outside the household. Also, a positive correlation was found between the number of daily smoked cigarettes and relative eosinophile count. These results suggest that passive smoking might have an effect on childhood asthma. There is an obvious difference in the sensitivity of the observed parameters, but despite the small number of patients in this research, it was still possible to find a significant difference in some of the parameters. This way we can explain why the values of ECP and relative eosinophile count showed a statistically significant difference while other observed parameters did not. It is possible that in a larger number group of patients, other parameters would also show statistically significant difference.

Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers

Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering. Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 clusterhad a TH17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence.In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE. Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.

EOSINOPHIL CATIONIC PROTEIN IN UREMIC DIALYZED PATIENTS WITH INTRACTABLE PRURITUS

We have analyzed 6 patients(pts) with chronic uremic pruritus(UPG) treated with intermittent hemodialysis more than 5 years,and 7 uremic pts treated under the same conditions but without pruritus(UG).In all pts and in appropriate control group(CG)of healthy subjects(N 0 = 5)we have measured the serum concentration of s.c.eosinophil cationic protein(ECP) known as a protein of allergic states(bronchial asthma as a classic example).We have found elevated serum concentrations of ECP in uremic pts(XECP cg = 2.03±0.02 µg/L vs X ECP ug = 2.63 ±0.29 µg/L),but especially at the uremics with intractable itching(X ECP upg = 8.37±1.67 µg/L). The aim pf the paper:The dialyzed pts with transitory uremic pruritus(u.p)or itching related to the other additioned conditions (like hepatocellular or obstructive jaundice)not differ significantly from the uremics without itching bearing in consi- deration the serum concentration of ECP. Material and methods:1.patients and control group: we have analyzed 6 patients(pts)with chronic imperative u.p(duration more than 6 months!)treated with intermittent hemodialysis more than 5 years(Department of nephrology,Clinical Centre,Skopje,R.of Macedonia) and 7 uremics treated under the same conditions but without up.In all pts(age and sex matched,N 0 = 13)and in the appropriate control group of healthy subjects(c.g,N 0 = 5),we have measured the serum concentrations of s.c.eosinophil cationic protein(ECP)known as a protein of allergic states(allergic rhinitis and conjunctivitis,atopic dermatitis and bronchial asthma as a classic example).The blood was picked up at 8 a clock for investigated persons and before hemodialysis for uremic pts to.Results: From the precedent tables is evident almost the same frequency in men and women(males = 10,females=8),with the mean age(all groups included) of about 44 years.The serum concentration of ECP is lowest(≈ 2 µg/l) in the CG with coefficient of variation(CV) under 2%!The UG is not so compact regarding sECP with CV ≈ 30%,and finally the uremic pts suffering from intractable itching(UPG) are heterogenous group with more elevated level of sECP(at p 1.96 SEM) but especially evident comparing the CG and UPG(Z= 3.8 SEM),respectively UG and UPG(Z >3.3 SEM).We have concluded that in the cases of very promounted u.p,the allergic component is higly included.The further investigations are needed to detect indoubtely the presence of ECP,EPX or eosinophils in the selected planes of the skin tissue and to develop more efficacious antipruritus drugs. Index trems: uremic intractable pruritus eosinophil cationic protein(ECP),Hemodialysis