Type 2 high asthma phenotype in children: A multidimensional clustering analysis.

Eosinophil cationic protein (ECP) is a cytotoxic agent secreted by activated eosinophils during allergic and inflammatory processes. The aim of the study was to determine the ECP level, absolute and relative eosinophil count and IgE antibodies in children with atopic dermatitis (AD) compared with those of nonatopic children, and to assess the correlation of these laboratory parameters with the clinical severity of AD. This prospective study comprised 70 children. There were 49 children with AD aged 3-36 months, and the control group comprised 21 children with a negative personal and family history for atopic diseases. Detailed history, serum ECP levels (UniCAP FEIA), relative and absolute eosinophil counts and total serum IgE antibodies were determined in both groups. In the children with AD, skin involvement was measured by the SCORAD index. The calculated SCORAD index was between 16 and 83. IgE antibodies, relative and absolute eosinophil counts showed a significantly wider range of values and a statistically higher median (P < 0.001) in the patients with AD compared with the control group. These laboratory parameters did not correlate with the severity of AD. The serum ECP median level, in the children with AD, was 16.2 microg/L (range 3.01-65.30) compared with 5.92 microg/L (range 2.76-21.90) in the control group. Correlation of the total SCORAD index and the serum ECP levels was negative, weak (r = -0.065) and statistically not significant (P > 0.05). The same was found for the correlation of serum ECP and intensity of skin changes (r = -0.095) and serum ECP and subjective symptoms (r = -0.045). The correlation was positive, but weak and statistically not significant for the serum ECP and extent of the skin lesions (r = 0.079, P > 0.05). Elevated levels of ECP, relative and absolute eosinophil counts, as well as IgE antibodies were determined in the patients with AD. As these laboratory findings did not correlate with the severity of AD, they can be considered only as additional methods in the evaluation of patients with AD.

Potential of Blood Eosinophils, Eosinophil-Derived Neurotoxin, and Eotaxin-3 as Biomarkers of Eosinophilic Esophagitis

Esophageal histology is critical for diagnosis and surveillance of disease activity in eosinophilic esophagitis (EoE). A validated noninvasive biomarker has not been identified. We aimed to determine the utility of blood and urine eosinophil-associated proteins to diagnose EoE and predict esophageal eosinophilia. Blood and urine were collected from children undergoing endoscopy with biopsy. Absolute eosinophil count (AEC), plasma eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein-1 (MBP-1), galectin-10 (CLC/GAL-10), Eotaxin-2 and Eotaxin-3, and urine osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) were determined. Differences were assessed between EoE and control, and with treatment response. The capacity to predict EoE diagnosis and esophageal eosinophil counts was assessed. Of 183 specimens were collected from 56 EoE patients and 15 non-EoE controls with symptoms of esophageal dysfunction; 33 EoE patients had paired pre- and post-treatment specimens. Plasma (CLC/GAL-10, ECP, EDN, Eotaxin-3, MBP-1) and urine (OPN) biomarkers were increased in EoE compared to control. A panel comprising CLC/GAL-10, Eotaxin-3, ECP, EDN, MBP-1, and AEC was superior to AEC alone in distinguishing EoE from control. AEC, CLC/GAL-10, ECP, and MBP-1 were significantly decreased in patients with esophageal eosinophil counts <15/hpf in response to treatment. AEC, CLC/GAL-10, ECP, EDN, OPN, and MBP-1 each predicted esophageal eosinophil counts utilizing mixed models controlled for age, gender, treatment, and atopy; AEC combined with MBP-1 best predicted the counts. We identified novel panels of eosinophil-associated proteins that along with AEC are superior to AEC alone in distinguishing EoE from controls and predicting esophageal eosinophil counts.

Objective. To determine the effect of prolonged endurance exercise on the serum concentrations of eosinophil cationic protein (ECP), immunoglobulin E (IgE) and upper respiratory tract symptoms (URTS). Design. In 11 healthy, experienced volunteers (6 males, 5 females, age 43 ± 9.8 years) the serum concentrations of ECP and IgE were measured, 24 hours prior to projected finishing time, immediately post exercise (IPE), and 3 h, 24 h, and 72 h after an ultramarathon (90 km). Self-reported URTS were also recorded for 14 days after the race. ECP was measured using radioimmunoassay and IgE using the Alastat Microplate Total IgE kit. The after-exercise values were corrected for plasma volume changes, which were calculated from haematocrit and haemoglobin values. Serum concentrations of ECP and IgE were analysed using an analysis of variance (ANOVA) comparing values with before-exercise levels. Level of significance was set at p ≤ 0.05. Results. ECP was significantly elevated at 72 hours (+52%), whilst IgE was not significantly altered after the ultramarathon. There were no reported URTS for the 14 days after the race. Conclusion. The eosinophil is a pro-inflammatory leukocyte involved in bronchial hyperreactivity and allergic inflammation of the airways. IgE is associated with allergic diseases such as asthma and rhinitis. Serum ECP is a sensitive marker of eosinophil activation. The result provides evidence for the non-allergic activation of blood eosinophils during prolonged endurance exercise. Whether this indicates exercise or environmentally induced airway inflammation, or a role for ECP in muscle /tissue repair, are hypotheses that require additional research. SA Sports Medicine Vol.16(2) 2004: 12-16

What drives the allergic march?

Objective. To determine the effect of prolonged endurance exercise on the serum concentrations of eosinophil cationic protein (ECP), immunoglobulin E (IgE) and upper respiratory tract symptoms (URTS). Design. In 11 healthy, experienced volunteers (6 males, 5 females, age 43 ± 9.8 years) the serum concentrations of ECP and IgE were measured, 24 hours prior to projected finishing time, immediately post exercise (IPE), and 3 h, 24 h, and 72 h after an ultramarathon (90 km). Self-reported URTS were also recorded for 14 days after the race. ECP was measured using radioimmunoassay and IgE using the Alastat Microplate Total IgE kit. The after-exercise values were corrected for plasma volume changes, which were calculated from haematocrit and haemoglobin values. Serum concentrations of ECP and IgE were analysed using an analysis of variance (ANOVA) comparing values with before-exercise levels. Level of significance was set at p ≤ 0.05. Results. ECP was significantly elevated at 72 hours (+52%), whilst IgE was not significantly altered after the ultramarathon. There were no reported URTS for the 14 days after the race. Conclusion. The eosinophil is a pro-inflammatory leukocyte involved in bronchial hyperreactivity and allergic inflammation of the airways. IgE is associated with allergic diseases such as asthma and rhinitis. Serum ECP is a sensitive marker of eosinophil activation. The result provides evidence for the non-allergic activation of blood eosinophils during prolonged endurance exercise. Whether this indicates exercise or environmentally induced airway inflammation, or a role for ECP in muscle /tissue repair, are hypotheses that require additional research. SA Sports Medicine Vol.16(2) 2004: 12-16

The diagnosis and management of eosinophilic esophagitis (EoE) often requires multiple endoscopies. Serum biomarkers can be elevated in EoE patients, but their clinical utility in diagnosis and assessing response to treatment is not well established. To evaluate serum biomarkers in EoE subjects compared with controls and assess longitudinally in response to treatment. We conducted a prospective cohort study of children and adults undergoing esophagogastroduodenoscopy for suspected EoE. After completing an 8-week course of proton-pump inhibitor therapy, esophageal mucosal biopsies were obtained, as well as, serum analysis of absolute eosinophil count (AEC), eotaxin-3, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and interleukin-5. Subjects with normal endoscopic and histologic findings constituted controls. Those meeting criteria for EoE underwent repeat esophagogastroduodenoscopy and biomarker measurements following treatment with topical steroids for 8 weeks. Median levels of AEC (263.50 vs. 102 cu/mm, P<0.001), ECP (26.98 vs. 5.20 ng/mL, P<0.001) and EDN (31.70 vs. 14.18 ng/mL, P=0.004) were significantly elevated in EoE subjects compared with controls and correlated with esophageal eosinophilia. Levels of AEC (odds ratio, 1.79; 95% confidence interval, 1.28-2.64) and ECP (odds ratio, 1.61; 95% confidence interval, 1.23-2.36) were associated with a diagnosis of EoE. Among the 5 biomarkers evaluated, only AEC significantly predicted esophageal eosinophilia following topical steroid therapy in EoE subjects (P=0.006). AEC, ECP, and EDN were higher in EoE subjects compared with controls and correlated with degree of esophageal eosinophilia. Furthermore, AEC predicted post-treatment eosinophilia, suggesting a potential role in monitoring EoE disease activity.

Atopic asthma is associated with elevated type-2 biomarkers such as fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count. However, increased type 2 markers have also been reported in traditionally defined non-atopic asthma. To determine a clinically useful level of IgE sensitization for ruling out type 2 asthma. Asthmatics (N=408; age 10-35years) were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP). Subjects were grouped based on IgE-antibody concentrations: ≥0.35kUA /L for at least one test (n=326) or <0.35kUA /L for both tests (n=82). Τhe latter group was subsequently divided into 2 groups: IgE 0.10-0.34kUA /L (n=34) and IgE<0.10kUA /L (n=48). The relationships between type 2 biomarkers, and inadequate asthma control (ACT<20), reduced lung function (FEV1 <80%), recent asthma attacks and airway hyperresponsiveness (AHR) to methacholine were determined. In univariate analyses, at least one type 2 marker related to each asthma outcome in subjects with IgE ≥0.35kUA /L. In subjects with IgE 0.10-0.34kUA /L, elevated FeNO related to reduced lung function (P=.008) and B-Eos to AHR (P=.03). No associations were found in subjects with IgE<0.10kUA /L. In multivariate analysis, a relationship between FeNO and reduced lung function remained in subjects with IgE<0.35kUA /L (P=.03). Clinically relevant elevation of type 2 biomarkers was seen in young asthmatics with IgE antibodies <0.35kUA /L, but not those with IgE<0.10kUA /L. It seems possible to define non-type 2 asthma through sensitive IgE-antibody measurement.

Background: Allergen sensitization is a risk factor for the development of bronchial asthma in adults. However, the relationship between allergen sensitization and lung function in asthma patients is not well understood. This study was conducted to evaluate the relationship between sensitized allergens, total serum immunoglobulin E (IgE) level, and lung function in adult asthmatic patients in northern Taiwan.Methods: A total of 266 adult Taiwanese patients diagnosed with asthma between January 2003 and December 2004 were enrolled. Age, sex, duration of asthma, pulmonary function tests, total IgE, eosinophilic cationic protein, and specific IgE of ImmunoCAP were recorded. Allergic was defined as the presence of a specific IgE to 1 or more allergens.Results: There were 161 (60.5%) male and 105 (39.5%) female patients, with a mean age of 60.46 ± 15.40 years. The mean duration of asthma was 13.64 ± 7.35 years. Mite allergens, Dermatophagoides pteronyssinus (48.46%) and Dermatophagoides farina (49.23%), were the most common indoor allergens. We divided the patients into allergic and nonallergic asthma groups: 164 (61.7%) patients had allergic asthma and 102 (38.3%), nonallergic asthma. Patients with allergic asthma were younger, and had a higher total IgE level and better lung function than the nonallergic asthmatics (p＜0.05, respectively). Total serum IgE was correlated to peak expiratory flow (PEF) variability (r=0.3395, p＜0.0001) in asthmatic patients. Among allergic asthmatics, the serum total IgE and PEF variability were higher as the number of positive allergen-specific IgE tests increased.Conclusions: Defining asthma phenotypes as allergic or nonallergic is essential. This study supports the difference between allergic and nonallergic asthma. Patients with allergic asthma were younger and had higher total IgE and better lung function than patients with nonallergic asthma.

The aim of the present study was to analyze the diagnostic accuracy of serum eosinophilic cationic protein (ECP) for eosinophilic esophagitis (EoE) and the correlation of ECP with clinical, histopathological, laboratory, and endoscopic features of EoE. Fifteen patients with EoE and 14 healthy controls were included in the study. Demographic parameters were recorded. EoE Endoscopic Reference Score (EREFS) was calculated according to endoscopic features, and esophageal biopsies were obtained by a single experienced endoscopist in a patient group. Serum ECP levels (μg/mL), absolute eosinophil count (U/mm3), and maximum peak of eosinophils/high-power field in esophageal biopsies were analyzed. The median age of all participants was 33.0 (min-max: 18-46) years. There were 27 (93.1%) male patients. Serum ECP level was significantly higher in patients with EoE than in healthy volunteers (20.4 vs. 8.8, p<0.0001). According to the receiver operating characteristic (ROC) curve analysis, ECP had 80% sensitivity and 92.8% specificity to diagnose EoE with a cut-off value of 13.9 µg/mL (area under the ROC curve 0.895; p<0.0001; 95% CI: 0.725-0.978). EREFS (p<0.0001) and the presence of food impaction (p=0.04) were significantly correlated with ECP. Serum ECP is an accurate non-invasive biomarker for EoE with high specificity and sensitivity. In addition, ECP is strongly correlated with EREFS and the symptom of food impaction.

Background: There are few data on asthma risk factors and phenotypes in patients with seasonal allergic rhinitis (SAR). Methods: Thirty-three children (mean age, 8.27 ± 1.77 years) and 82 adults (mean age, 34.12 ± 10.59 years) with SAR were evaluated for asthma (history, reversibility of bronchial obstruction, increased inhaled nitric oxide). The following asthma risk factors were considered in the multiple regression analysis: male sex, family history of asthma, breastfeeding < 2 months, passive/active smoking, obesity, pets/molds exposure, high total serum immunoglobulin E (IgE), polysensitization (sensitized to 3 seasonal pollens with different structure), mixed sensitization (seasonal and perennial allergens), severe rhinitis (according to the Allergic Rhinitis and its Impact on Asthma guidelines), and lack of allergen-specific immunotherapy (SIT) for rhinitis preceding asthma diagnosis. Asthma phenotypes were characterized using the k-means clustering (silhouette method for cluster validation). Results: Asthma was diagnosed in 22 (66.7%) children and in 57 (69.5%) adults with SAR. Independent risk factors for asthma were lack of SIT preceding asthma diagnosis, both for children (P = 0.008132) and adults (P = 0.000017), and mixed sensitization for children (P = 0.035694). Asthma phenotypes identified in children according to the associated risk factors were: breastfeeding < 2 months and severe rhinitis in 16 (63.6%) patients; male, polysensitized, and severe rhinitis in 8 (36.4%) patients. Asthma phenotypes in adults were: polysensitization and severe rhinitis in 30 (52.6%) patients; male, exposure to pets, and severe rhinitis in 11 (19.3%) patients; and high total serum IgE and polysensitization in 16 (28.1%) patients. Conclusion: Lack of SIT is an independent risk factor for asthma both in children and adults with SAR, whereas polysensitization is a risk factor only for children. The dominant asthma phenotype in children with SAR is breastfeeding < 2 months and severe rhinitis. In adults with SAR, the dominant asthma phenotype is polysensitization and severe rhinitis.

A randomized, double-blind trial of the effect of treatment with formoterol on clinical and inflammatory parameters of asthma in children

Background: Asthma is a clinical syndrome characterized by recurrent episodes of airway obstruction, bronchial hyperresponsiveness and airway inflammation. Most patients with asthma present a “type 2” (TH2) inflammation. ILC2 and TH2 cells release cytokines IL4, IL-13 and IL-5. CRSwNP is a condition characterized by hyposmia or anosmia, nasal congestion, nasal discharge, and face pain or pressure that last for at least 12 weeks in a row without relief. Both asthma and CRSwNP are often characterized by a type 2 inflammation endotype and are often present in the same patient. Dupilumab is a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, blocking IL4/IL-4Rα binding and IL13. It has been labelled for the treatment of moderate to severe asthma in patients from the age of 12 years with an eosinophilic phenotype, and it has demonstrated efficacy and acceptable safety. Our study aims to investigate the effects of dupilumab on type 2 inflammatory biomarkers, such as eosinophils and eosinophil cationic protein (ECP). ECP is an eosinophil-derived substance contained in granules that are released during inflammation and causes various biological effects, including tissue damage in asthmatic airways. Methods: ECP, Eosinophil counts (EOS), and total immunoglobulin E (IgE) levels were longitudinally measured using immunoassays in the serum of 21 patients affected by CRSwNP, of which 17 had asthma as a comorbidity, receiving 300 mg dupilumab every two weeks. Results: The EOS and ECP, after a first phase of significant increase due to the intrinsic characteristic of the block of IL-4 and IL-13, returned to the baseline 10 months after the initial administration of dupilumab. Fractional exhaled nitric oxide (FeNO) and serum total IgE decreased significantly after 9 months. Asthma Control Test (ACT) scores improved after dupilumab treatment. FEV1% and FEV1 absolute registered a significant improvement at 10 months. Conclusions: Patients who received 300 milligrams of dupilumab every two weeks first experienced a temporary increase in eosinophils (EOS) and eosinophil cationic protein (ECP), then exhibited a gradual decline in these variables with a subsequent return to the initial baseline levels. When compared to the baseline, we observed that the levels of IgE and FeNO decreased over time, while there was an increase in both FEV1 and FEV1%.

Allergy, is a clinical expression of soluble factors like IgE, histamine or eosinophils found in serum or plasma of such patients. The products that are responsible for allergy are called as Allergens. Allergens normally induce IgE production which leads to type 1 hypersensitivity response on subsequent exposure to the same allergen. The target organs are mostly nose, lung, skin and gastrointestinal tract. Atopy is also considered as a triad of Atopic dermatitis, allergic rhinitis and bronchial asthma. Raised serum IgE and AEC are proven indicators of allergic phenomenon. Various studies show relationship between serum Immunoglobulin E level and total eosinophil count in population suffering from allergic diseases. Serum total Immunoglobulin E, total eosinophil count and specific IgE are all helpful for the diagnosis and treatment of allergic diseases. Objectives: 1.To Evaluate Serum Total IgE level in Children with allergic diseases.2. To Evaluate Absolute Eosinophil Count (AEC) in children with allergic diseases.3. To Correlate Serum Total Immunoglobulin E Level and Absolute Eosinophil Count (AEC) with allergic diseases. Methodology: Cross sectional study with 100 children in the age group 2-12 years with nasopharyngeal allergies (like bronchial asthma and atopic rhinitis) and skin allergies (like atopic dermatitis, urticaria) ,eye allergies were enrolled and serum IgE levels and AEC levels was done. Results: In present study Absolute eosinophil count was raised in 58% of cases Serum IgE was raised in 54% of cases. In present study, of 58% cases with raised Absolute eosinophil count 81% (47 cases) showed raised serum IgE levels. Conclusion: Absolute eosinophil count and serum Total IgE has been considered as a significant marker of allergic state and can be used as a marker of allergic response in atopic individuals. Raised serum IgE and AEC are more in nasobronchial allergy as compare to other systemic allergies. The elevated level of serum Total IgE and Absolute Eosinophil Count both shows Significant Correlation thus can be considered as a dependable laboratory investigation in diagnosing and categorizing allergic diseases.

BackgroundIdiopathic hypereosinophilic syndrome currently represents a major unmet need for all medical specialties dealing with this disease. Markers capable of characterising the wide variability of its clinical presentation are currently lacking.ObjectiveThis study aims to evaluate a panel of possible markers in idiopathic hypereosinophilic syndrome.MethodsIn this pilot prospective single-centre cohort study, we analysed clinical (age, years of disease, steroid therapy) and laboratory (absolute eosinophil count, total IgE antibodies, IgE antibodies against Staphylococcus aureus enterotoxins, serum eosinophil cationic protein, serum immunoglobulin free light chains k and λ and their ratio) data obtained from 21 patients suffering from idiopathic hypereosinophilic syndrome from June 2023 to December 2024.ResultsMean absolute eosinophilic count was 3758.57 cells/μL. 17 patients were receiving treatment with > 7.5 mg of prednisone or equivalent at the time of the diagnosis. 13 patients had positive Staphylococcus aureus enterotoxins IgE, while the mean total serum IgE was 241.64 kU/L. We observed a high serum eosinophil cationic protein value as well as a high serum κ free light chain, while serum λ and κ/λ were normal. Patients with higher absolute eosinophilic count had higher eosinophil cationic protein levels (p < 0.05), such as higher steroid consumption (p < 0.05). In addition, we found a strong association between high κ free light chain levels and high previous steroid use and with Staphylococcus aureus enterotoxins IgE positivity.ConclusionOur results could increase the number of possible biomarkers for risk stratification in idiopathic hypereosinophilic syndrome.