Clinical case of association of food and pollen allergy with acne

Eosinophil-derived neurotoxin as a biomarker for disease severity and relapse in recalcitrant atopic dermatitis

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.

BackgroundMepolizumab, a humanized antibody targeting interleukin-5, decreases the number of blood eosinophils and the frequency of exacerbation of severe asthma. Galectin-10 is a protein within the cytoplasm of eosinophils and constitutes Charcot-Leyden crystals, which promotes key features of asthma. However, the relationship between time kinetics and clinical response of eosinophil-derived molecules such as galectin-10 or eosinophil cationic protein (ECP) has not been precisely investigated.ObjectiveThis study aimed to clarify the precise time course of the levels of serum galectin-10 and ECP after mepolizumab treatment and to analyze the relationship between the levels of eosinophil-derived molecules and the clinical background or response to mepolizumab treatment.MethodsThis multicenter, prospective open-label study recruited 20 patients with severe eosinophilic asthma. Mepolizumab was administered every 4 weeks for 32 weeks and the levels of various biomarkers were serially analyzed.ResultsThe serum galectin-10 and ECP significantly and rapidly decreased 4 weeks after initial administration of mepolizumab. In contrast, basophil count, fractional exhaled nitric oxide, and the serum total IgE level were unchanged during treatment. Asthma Control Questionnaire-5, Asthma Health Questionnaire-33, and Lund-Mackay scores significantly improved after mepolizumab treatment. Both high ECP and eosinophil count related to better response in forced expiratory volume in 1 second (FEV1) and measurable ECP level at 4 weeks after administration of mepolizumab related to the further improvement in FEV1 toward week 32. No significant difference in improvement in FEV1 was observed in galectin-10 high group. The level of ECP at baseline was significantly related to the higher prevalence of nasal polyp and Lund-Mackay score.ConclusionThis study was the first to show that the levels of serum galectin-10 decreases after initial administration of mepolizumab. The significant relationship between serum ECP and better response in FEV1 suggested the potential role of serum ECP as a predictive biomarker for the efficacy of mepolizumab (UMIN000030466).

Serum eosinophilic cationic protein and high sensitive C-reactive protein as alternative parameters for differentiation of severity stages and monitoring control in bronchial asthma patients

Eosinophil cationic protein (ECP) plays a significant role in the pathogenesis of atopic diseases such as allergic rhinitis (AR) and asthma. Using saliva as a diagnostic material is a non-invasive, simple method. Analysis of ECP in saliva was shown as an alternative diagnostic contribution in patients with asthma. In this study we aimed to assess a possible association between the levels of salivary ECP and the diagnosis of AR by comparing serum ECP and salivary ECP levels. Thirty-five allergic rhinitis patients (study group) sensitive to Dermatophagoides farinae (D2) in skin prick test (SPT) and 35 nonallergic, SPT negative, healthy volunteers (control group) were included in the study. Salivary ECP, serum ECP and specific IgE D2 levels were measured. Distribution of age and gender were similar in the study and the control groups (p>0.05). Serum specific IgE D2 levels were significantly higher in the study group compared to the control group (p<0.001). ECP levels in saliva and serum did not show any significant difference in between study and control groups (p=0.738; p=0.796, respectively). No significant difference was found between the levels of ECP in between the serum and the saliva of study and control groups. (p=0.504; p=0.589, respectively). There was no significant correlation between saliva and serum ECP levels of both groups.(r=-0.191/p=0.114). Serum and saliva ECP levels seem close to each other and were comparable in both groups, but we did not find any correlation between them Although we hypothesized that saliva ECP may be used as a non-invasive method for the diagnosis of AR, it seems that this parameter is not helpful in diagnosis of AR.

Level of serum neutrophil gelatinase-associated lipocalin in childhood asthma

Several laboratory parameters have been investigated for assessing disease activity in children with atopic dermatitis (AD). Analyses of the correlation between these parameters and clinical severity can help to choose a convincing tool. This study compared the significance of serum interleukin-16 (IL-16), serum total immunoglobulin E (IgE), serum eosinophil cationic protein (ECP), and total eosinophil count (TEC) in reflecting AD severity to order to identify the most relevant objective tool for assessing AD activity and to assess the correlation between these laboratory parameters. The Severity Scoring of Atopic Dermatitis (SCORAD index) was used for the assessment of disease activity in 48 pediatric patients in the acute exacerbation phase and in the maintenance phase after improvement of clinical findings with conventional treatment for 8 weeks. Serum levels of total IgE, ECP, and IL-16 as well as TEC were measured on the same time points and compared with healthy non-atopic controls. The correlation between SCORAD and each laboratory parameter was tested for significance and compared. Serum levels of ECP and IL-16 of AD patients were significantly higher than those of controls. These serum parameters, except TEC, declined significantly after conventional treatment with clinical improvement. There was positive correlation with SCORAD for serum IgE (r=0.317, p=0.028), TEC(r=0.434, p=0.002), IL-16 (r = 0.321, p=0.026) in the acute exacerbation phase and with SCORAD for serum IgE (r=0.510, p<0.001), TEC(r=0.489, p<0.001), serum ECP (r=0.468, p=0.001) in the maintenance phase. Serum levels of total IgE, IL-16, ECP, and TEC correlated with the SCORAD index in pediatric patients with atopic dermatitis. Thus, they can serve as serum markers for monitoring disease activity in childhood atopic dermatitis.

Staphylococcal enterotoxins can act as allergens and stimulate production of specific IgE with subsequent development of allergic manifestations. In addition, they act as superantigens that induce cytokine secretion with more increase of IL-4/IFN-γ ratio causing augmentation of allergic reactions. Herein we tested the hypothesis that exposure to Staphylococccus aureus and its enterotoxins induces immunological changes that contribute to the pathogenesis of allergic rhinitis and bronchial asthma. This study included 45 air way allergic patients, and 45 controls. The following were done: intradermal allergy skin testing, invitro effect of staphylococcal enterotoxin B (SEB) on cytokine secretion from separated peripheral blood mononuclear cells, detection of nasal carriage of S. aureus and its enterotoxin production by ELISA & serum levels of total IgE, SEB-specific IgE and eosinophil cationic protein (ECP) were measured. We found that nasal carriage of enterotoxin producing S. aureus in allergic patients was significantly higher than in control. Blood eosinophilia, total IgE& ECP levels were significantly higher in S. aureus nasal carrier than non-carrier patients. On in vitro exposure of PBMCs to (SEB), IFN-γ secretion was significantly less in patients than control and IL-4 secretion was significantly more in patients than control. SEB-specific IgE was detected in 15.6% of patients & not detected in control. There was a significant positive correlation between SEB-specific IgE level in patients and markers of severity of allergic reaction including blood eosinophilia, ECP and total IgE level. This study suggests that nasal carriage of enterotoxin producing S. aureus has a potential role in the development and severity of allergic airway diseases.

Age-related differences in the pathogenesis of chronic rhinosinusitis

Newborns with jaundice requiring or not requiring phototherapy (PT) are at greater risk of developing asthma later in life. In this study, we investigated the effect of PT treatment on eosinophil and eosinophilic cationic protein (ECP) levels in newborns with severe hyperbilirubinemia. Thirty newborns diagnosed with severe hyperbilirubinemia and exposed to light-emitting diode (LED) PT were enrolled into the study. Total serum bilirubin (TSB) levels, complete blood count and serum ECP concentrations were measured before and after PT. TSB and hemoglobin (Hb) counts were lower after PT (p = 0.001). There was no difference between leukocyte, lymphocyte, neutrophil and platelet count before and after PT. Eosinophil levels were increased after PT, although not significantly. ECP levels were higher after PT (p = 0.006). It may be speculated that newborns treated with LED PT, increased ECP might play a role in developing allergic diseases later in life.

Serum ECP and total IgE levels in children with acute laryngotracheobronchitis

To investigate the relationships between the severity of childhood allergic rhinitis (AR) and the peripheral blood eosinophil count, serum eosinophil cationic protein (ECP), total IgE (tIgE), and allergen-specific IgE (sIgE) levels. A total of 138 children with AR aged 3 to 17 (9.96 ± 3.78, x() ± s) years old were enrolled in the study. All children had persistent AR sensitized to house dust mites with a clinical history of 3 months to 12 (4.21 ± 2.72) years. The disease severity was evaluated using 10 cm-visual analogue scale (VAS), and the serum levels of ECP, tIgE and sIgE were determined using an ImmunoCAP system. Statistical analysis was conducted with SPSS11.0 software. Among 138 children with AR, the VAS scores for global severity of rhinitis and nasal obstruction symptom were 5.32 ± 2.16 and 4.78 ± 2.45, respectively. Blood eosinophil count was 0.39 [0.24; 0.63] (M[P(25); P(75)]) ×10(9)/ml. Serum levels of ECP and total IgE were 10.60 [3.26; 30.80] µg/L and (2.50 ± 0.53) log kU/L, respectively. Serum levels of allergen-sIgE against Dermatophagoides pteronyssinus and Dermatophagoides farinae were 58.20[24.75; > 100] kUA/L and 54.95 [24.55; > 100] kUA/L, respectively. The VAS scores of nasal obstruction symptom, but not global severity of rhinitis, were positively related to the duration of AR (r = 0.215, P = 0.011) and the levels of serum ECP (r = 0.196, P = 0.022) in bivariate correlation analysis. There was also a significant correlation between the serum ECP level and the blood eosinophil count (r = 0.295, P = 0.000). No relationships of blood eosinophil count, and serum tIgE and sIgE levels with global severity of rhinitis as well as nasal obstruction symptom were found (all P > 0.05). These results suggested that the severity of nasal obstruction was positively correlated with the duration of rhinitis and the levels of serum ECP in childhood persistent AR due to house dust mites, indicating the disease severity might be related to chronic inflammatory process.

In chronic eosinophilic pneumonia (CEP), histopathological evidence exists for the degranulation of eosinophils and the release of various toxic proteins. In vitro studies have demonstrated the degranulation of eosinophils in response to aggregated and complexed immunoglobulins. The aims of this study were to investigate: 1) whether the eosinophil cationic protein (ECP) and immunoglobulin (Ig) levels in bronchoalveolar lavage (BAL) fluid from patients with CEP are increased compared to those of healthy controls; 2) and whether a relationship is present between immunoglobulin levels and ECP levels in BAL fluid from patients with CEP. The BAL from 12 patients with CEP was selected, retrospectively, from all BAL analyses performed in our centre between 1986 and 1992. ECP levels were measured using a radioimmunoassay in BAL fluid of patients with CEP and 10 healthy controls. ECP levels and immunoglobulin levels in BAL fluid from patients with CEP were found to be elevated compared to controls (p < 0.001). A relationship was found between IgA levels and ECP levels in BAL fluid from patients with CEP (r = 0.72; p = 0.043). In conclusion, eosinophil cationic protein and immunoglobulin levels were found to be increased in bronchoalveolar lavage fluid from patients with chronic eosinophilic pneumonia. The relationship found between immunoglobulin A levels and eosinophil cationic protein levels may suggest that immunoglobulin A could be involved in the degranulation of eosinophils in chronic eosinophilic pneumonia.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease. The pathogenesis of CRSwNP remains unclear. This study was designed to investigate the role of inflammation and Staphylococcus aureus enterotoxin (SE) in this disease. The study included a total of 74 patients with CRSwNP and 6 controls. A serum Phadiatop assay was conducted to detect atopy status, and serum eosinophil cationic protein (ECP) and total immunoglobulin (Ig)E levels were determined using ELISA. SEA, SEB, total IgE, ECP and myeloperoxidase (MPO) levels in nasal tissue supernatant were measured using ELISA. The results indicated that 15 (22.1%) patients had systemic allergies. On the basis of the ECP/MPO ratio, the patients were divided into an eosinophilic CRSwNP group (n=18) and a non-eosinophilic CRSwNP group (n=56). The total ECP/MPO ratio was 0.572, with a notable bias toward neutrophilic inflammation. The supernatant ECP and MPO levels were elevated in the CRSwNP group compared with the control group, but no significant difference in the serum total IgE and ECP levels were observed between the CRSwNP and control groups. In addition, the non-eosinophilic and eosinophilic CRSwNP groups showed significant elevations in supernatant total IgE, SEA and SEB levels compared with the control group. Thus, it may be concluded that allergy is a common pathogenesis of CRSwNP, and neutrophilic inflammation is present in most Chinese CRSwNP patients. Additionally, local indicators reflect the inflammatory status more accurately than do serum indicators. SEs may act as an infection factor rather than as a superantigen in Chinese non-eosinophilic CRSwNP patients. Thus, long-term antibiotic therapy may be an option for Chinese non-eosinophilic CRSwNP patients.

Bronchial hyperactivity, a key feature of active asthma in children, is a risk factor for respiratory adverse events in the peri-operative period. The presence of activated eosinophils in the lungs and mast cell degranulation can contribute to bronchial hyperreactivity. Eosinophil cationic protein is released by activated eosinophils and tryptase reflects mast cell degranulation. This study focused on the relationship of respiratory mechanics, eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid in asthmatic and healthy children under general anaesthesia. We measured eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid from 21 asthmatic and 21 healthy children following induction of general anaesthesia. Respiratory system resistance and dynamic compliance were measured during mechanical ventilation. Eosinophil cationic protein was more common in bronchoalveolar lavage fluid from asthmatics (12/21) than from controls (4/21, p = 0.01) and was present at higher levels (p = 0.002). Tryptase was also more common in the asthmatics (8/21 vs 1/21, p = 0.01). Respiratory resistance was significantly higher in asthmatic children with detectable eosinophil cationic protein levels than in those with undetectable eosinophil cationic protein levels (p = 0.019). Furthermore, 50% of the asthmatics with detectable eosinophil cationic protein exhibited bronchospasm after sampling their bronchoalveolar lavage fluid. These findings suggested that high levels of eosinophil cationic protein in the bronchoalveolar lavage fluid are associated with irritable airways, presumably secondary to airway inflammation, and this might be a useful marker for respiratory adverse events in the peri-operative period.