Eosinophilic Group Research Articles

Clinical and Economic Burden of Elevated Blood Eosinophils in Patients With and Without Uncontrolled Asthma.

The European Respiratory Society and American Thoracic Society (ERS/ATS) published guidelines in 2014 for the evaluation and treatment of asthma. These guidelines draw attention to management of patients with asthma that remains uncontrolled despite therapy. One phenotypic characteristic of therapy-resistant asthma is eosinophil elevation. It is important to better understand the burden of care gaps in this patient subgroup in order to support improved treatment strategies in the future. To quantify the economic burden of asthma patients with and without peripheral blood eosinophil elevation. A retrospective cohort study was conducted using data from patients aged 12 years or older with a diagnosis of asthma using electronic health records of over 2 million patients between 2004-2010. Patients with a diagnosis of chronic obstructive pulmonary disease, Churg Strauss syndrome/Wegener's granulomatosis, eosinophilia, cystic/pulmonary fibrosis, allergic bronchopulmonary aspergillosis, or lung cancer in the 12-month period before the date of asthma diagnosis were excluded. Patients with asthma were followed for 12 months after their initial asthma diagnosis to identify those with controlled versus uncontrolled asthma based on ERS/ATS criteria. Patients with at least 1 peripheral blood eosinophil test result of ≥ 400 cells/µL were classified as those with elevated eosinophils. Total annual paid-claim cost was compared by eosinophil levels within the controlled and uncontrolled asthma subgroups. Costs were adjusted to 2015 U.S. dollars. Patients were stratified by control level, and generalized linear modeling regressions were used to assess the magnitude of increase in cost of the elevated eosinophil group. A total of 2,701 patients were included in the study, of which 17% had uncontrolled asthma and 21% had elevated eosinophils. The mean total annual cost of patients with uncontrolled asthma was more than 2 times the cost of those with controlled asthma ($18,341 vs. $8,670, P < 0.001). Patients with uncontrolled asthma in the elevated eosinophil group had almost double the total cost ($28,644 vs. $14,188, P = 0.008) compared with those with blood eosinophil levels in a normal range. Similarly, patients classified as those with controlled asthma in the elevated eosinophil group had almost twice the average costs as those without elevated eosinophils ($14,754 vs. $7,203, P < 0.001). Uncontrolled asthma with elevated eosinophils had 4 times greater hospital admissions and over 4 times higher total costs than controlled asthma without elevated eosinophils. Among patients with uncontrolled asthma, patients with elevated eosinophils had a 53% increase in mean cost ($17,723 vs. $11,581, P < 0.001) compared with patients without elevated eosinophils. Among patients with controlled asthma, patients with elevated eosinophils had a 62% increase in mean cost ($8,897 vs. $5,486, P < 0.001) compared with patients without elevated eosinophils. Elevated peripheral blood eosinophil level is associated with higher cost irrespective of disease control status. This study was funded by Teva Pharmaceuticals. Dotiwala and Casciano report consulting and writing fees from Teva Pharmaceuticals for work on this study. Sun is an employee and stockholder of Teva Pharmaceuticals. Li reports consulting fees from eMAX Health. All authors contributed to study design. Dotiwala took the lead in data collection, along with the other authors, and data interpretation was performed primarily by Krishnan, Sun, and Li, along with Casciano and Dotiwala. The manuscript was written by Casciano, Dotiwala, and Li, along with Sun and Krishnan, and revised by Casciano, Dotiwala, Sun, and Li, with assistance from Krishnan.

Value of blood eosinophilia in phenotype-directed corticosteroid therapy of COPD exacerbation: Final results

In COPD, clinically relevant exacerbation phenotypes, such as “eosinophilic” and “bacterial”, can be identified with simple biomarkers. Studies are needed to validate the use of these biomarkers to direct therapy for acute exacerbation (AECOPD). SettingChest Department, Assiut University Hospital. ObjectiveTo evaluate the use of blood eosinophilia in directing steroids therapy in AECOPD. DesignThis study included 71 COPD patients with 106 exacerbations. The bacterial exacerbation phenotype received antibiotic based therapy for 7days and eosinophilic exacerbation phenotype received antibiotic+oral prednisolone. Responses were recorded on days 7–14. ResultsThere was significant improvement in pulmonary function, arterial blood gases in both groups in day 7, 14 compared to admission. The improvement of FEV1, eosinophilic percentage and count, C-reactive protein, Cor-Pulmonale and PaO2 was more significant in eosinophilic phenotype. There was no difference in parameters of treatment failure and patient’s outcome between bacterial exacerbations who did not receive prednisolone compared to eosinophilic group. ConclusionIn AECOPD, it would be valuable to suggest that blood eosinophilia (>2%) is a simple accessible routine biomarker to identify phenotypes that actually need to add oral steroid to their management, and those for which there is a greater risk of harm.

Different roles of Staphylococcus aureus enterotoxin in different subtypes of nasal polyps.

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.

Interleukin-33 induces mucin gene expression and goblet cell hyperplasia in human nasal epithelial cells

We investigated whether IL-33 is involved in mucus overproduction and goblet cell hyperplasia in eosinophilic chronic rhinosinusitis (ECRS). IL-33 mRNA was significantly higher in the eosinophilic CRS group than in the non-eosinophilic CRS group from human nasal polyps. IL-33 induced MUC5AC mRNA and MUC5AC protein, and also goblet cell hyperplasia at air liquid interface culture in human nasal epithelial cells. In addition to that, IL-33 induced MUC5B and FOXA3, and reduces FOXJmRNA.In conclusion, our present study demonstrated that the direct evidence of IL-33 which lead to increase mucin gene and protein expression, as well as goblet cell hyperplasia. This study provides novel insights into the role of IL-33 on mucus overproduction in eosinophilic inflammation of human airways.

Eosinophils in COPD Exacerbations Are Associated With Increased Readmissions

A subset of patients with COPD demonstrates eosinophilic inflammation either in their sputum or blood. Previous studies regarding the association between increased blood eosinophil levels and poor readmission outcomes are conflicting. The goal of this study was to investigate outcomes following severe COPD exacerbations in patients with higher blood eosinophil levels. With an observational study design, data on hospitalizations for severe COPD exacerbation were retrospectively gathered. Patient health data previous to and up to 1 year following the index hospitalization were included. Patients were stratified into the eosinophilic group if the blood eosinophil level on admission was≥ 200 cells/μL and/or≥ 2%of the total WBC count. Clinical outcomes were 12-month COPD-related readmission, 12-month all-cause readmission, length of stay, and time to COPD-related readmission. These outcomes were analyzed by using logistic, negative binomial, and Cox regression models. A total of 167 patients were included; 55 had eosinophilia. Eosinophilia was associated with an increased risk of 12-month COPD-related readmission (OR, 3.59 [95%CI, 1.65-7.82]; P= .0013), an increased risk of 12-month all-cause readmission (2.32 [95%CI, 1.10-4.92]; P= .0277), and a shorter time to first COPD-related readmission (hazard ratio, 2.74 [1.56-4.83]; P= .0005). The length of stay was not statistically different between eosinophilic and noneosinophilic patients. Sensitivity analyses using different eosinophilia definitions revealed a proportional increase in effect size with increasing eosinophil cell count definitions for predicting 12-month readmissions. Blood eosinophil levels can be used as a biomarker in severe COPD exacerbations for predicting higher readmission rates.

Biologics in practice: A unique opportunity for allergist/immunologist expertise

Biologics in practice: A unique opportunity for allergist/immunologist expertise

Burden of asthma with elevated blood eosinophil levels.

BackgroundAsthma is a common chronic condition with an economic burden of almost $56 billion annually in the US. Biologic markers like blood eosinophils, that help predict the risk of exacerbation could help guide more optimal treatment plans and reduce cost. The purpose of this study was to determine whether healthcare resource use and expenditures vary by eosinophil level among patients with asthma.MethodsPatients with a diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011 were extracted from EMRClaims + database (eMAX Health, White Plains NY). Patients were classified as mild, moderate, or severe by medication use following diagnosis, based on recommendations of National Institutes of Health Expert Panel Report 3. Patients were classified as those with elevated eosinophils (≥400 cells/μL) and normal eosinophil level (<400 cells/μL). Patients were followed for resource use, defined as hospitalizations, ER visits and outpatient visit and associated costs were calculated to assess whether an economic difference exists between eosinophil groups. Non-parametric tests were used to compare resource use and associated cost between elevated and normal eosinophil groups. Multivariate modeling was performed to assess the contribution of eosinophil level on the likelihood of study outcomes among patients with severe asthma.ResultsAmong the 2,164 patients meeting eligibility criteria, 1,144 had severity designations. Of these, 179(16 %) of patients had severe asthma of which 20 % (n = 35) had elevated eosinophils. Seventeen percent of patients with elevated eosinophils were admitted to the hospital during the follow-up period, significantly greater than patients with normal eosinophil levels (12 %; p = 0.011). Overall, compared to patients with normal eosinophil levels (n = 1734), patients with elevated eosinophil levels (n = 430) had significantly greater mean annual hospital admissions (0.51 vs. 0.21/year, p = 0.006) and hospital costs (2,536 vs. $1,091, p = 0.011). Logistic regressions showed that elevated eosinophil level was associated with 5.14 times increased odds of all cause admissions (95 % CI:1.76–14.99, p = 0.003) and 4.07 times increased odds of asthma related admissions (95 % CI: 1.26–13.12, p = 0.019).ConclusionEosinophil elevation was associated with greater healthcare resource use in patients with asthma.

The utility of inflammatory markers to predict readmissions and mortality in COPD cases with or without eosinophilia

BackgroundCOPD exacerbations requiring hospitalization increase morbidity and mortality. Although most COPD exacerbations are neutrophilic, approximately 10%–25% of exacerbations are eosinophilic.AimWe aimed to evaluate mortality and outcomes of eosinophilic and non-eosinophilic COPD exacerbations and identify new biomarkers that predict survival.MethodsA retrospective observational cohort study was carried out in a tertiary teaching hospital from January 1, 2014 to November 1, 2014. All COPD patients hospitalized with exacerbations were enrolled in the study at their initial hospitalization and followed-up for 6 months after discharge. Electronic data were collected from the hospital database. Subjects’ characteristics, hemogram parameters, CRP levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-mean platelet volume ratio on admission and discharge, length of hospital stay (days), readmissions, and mortality were recorded. Patients were grouped according to peripheral blood eosinophil (PBE) levels: Group 1, >2% PBE, eosinophilic; Group 2, non-eosinophilic ≤2%. Patient survival after hospital discharge was evaluated by Kaplan–Meier survival analysis.ResultsA total of 1,704 patients hospitalized with COPD exacerbation were included. Approximately 20% were classified as eosinophilic. Six-month mortality was similar in eosinophilic and non-eosinophilic groups (14.2% and 15.2%, respectively); however, the hospital stay length and readmission rate were longer and higher in the non-eosinophilic group (P<0.001 and P<0.01, respectively). CRP and NLR were significantly higher in the non-eosinophilic group (both P<0.01). The platelet-to-mean platelet volume ratio was not different between the two groups. Cox regression analysis showed that survival was negatively influenced by elevated CRP (P<0.035) and NLR (P<0.001) in the non-eosinophilic group.ConclusionNon-eosinophilic patients with COPD exacerbations with high CRP and NLR values had worse outcomes than eosinophilic patients. PBE and NLR can be helpful markers to guide treatment decisions.

Immunodiagnostic approaches for the detection of human toxocarosis

Human toxocarosis is an important zoonosis caused by larvae of Toxocara canis/cati. The objective was to evaluate the role of IgG anti-Toxocara antibody detection and the specific IgG avidity in diagnostics of human toxocarosis. Anti-Toxocara IgG antibodies and IgG avidity were evaluated by excretory-secretory (ES)-enzyme-linked immunosorbent assay (ELISA). The IgG anti-Toxocara seroprevalence in people (n = 7678) from western Slovakia was 15.3% and found to be highest in the oldest age groups. The presence of low- IgG avidity in 179 suspected patients for toxocarosis was evaluated in relation to sex, age, IgG antibody levels, eosinophilia, increased total IgE, domicile, geophagia, dog/cat ownership, anamnesis. Low- IgG avidity index was found in 30.7% of the patients. The low- IgG avidity in eosinophilic group (42.1%) was significantly higher than in non-eosinophilic group (22.0%; P = 0.043). Substantially higher eosinophilia was detected in children (under 10 years old; 55.6%) than in adults (aged ≥ 41 years; 17.6%; P = 0.009). Significant difference between seroprevalence of total IgE in patients coming from towns (48.8%) and patients from villages (21.3%) was established (P = 0.007). Mild negative correlation (r = −0.477, P = 0.043) was observed between the amounts of eosinophils and the values of IgG avidity. The sensitivity and specificity of IgG avidity assay were 43.8% and 83.3%, respectively. Our results suggest that besides anti-Toxocara IgG, measurement of IgG avidity may be useful for the determination of acute toxocarosis. Moreover, these tests should be accompanied by other immunological markers and determinants of examined patients such as eosinophilia, increased total IgE and age.

Seroepidemiology of Toxocariasis and Its Clinical Implications in Gwangju and Jeonnam-province, Korea.

We investigated the seroepidemiological, clinical, and laboratory characteristics of patients suspected to have toxocariasis in Gwangju and Jeonnam-province, Korea. In total, 228 specimens were analyzed for anti-Toxocara canis IgG at two university hospitals from 2010 to 2012. The overall seropositive rate was 67.1%, and the seropositive rates among the eosinophilic and non-eosinophilic groups were 76.1% (105/138) and 53.3% (48/90), respectively. Risk factors for eosinophilia and toxocariasis were male sex (odds ratios [OR]=2.632 and 3.477, respectively) and a history of ingesting raw meat (OR=2.884 and 3.274, respectively), especially raw cow liver (OR=2.089 and 10.038, respectively). T. canis seropositivity (OR=5.807, P=0.004) and a history of consuming raw cow liver (OR=2.766, P=0.052) were risk factors for organ involvement. The anti-T. canis IgG level showed weakly positive correlations with eosinophil counts (r=0.234, P<0.001) and the duration of eosinophilia (r=0.155, P=0.019). Although limited to the regions of Gwangju and Jeonnam-province, this study supports the opinion that toxocariasis is a reasonable focus as a cause of eosinophilia and that it is also associated with organ involvement.

Effectiveness of omalizumab in an asthmatic patient with severe airway and blood eosinophilia.

Omalizumab is a monoclonal antibody raised against class E immunoglobulin (IgE), approved for the treatment of chronic severe (in the EU) or moderate-to-severe (in the USA) IgE-mediated asthma. Omalizumab is effective in reducing asthma exacerbations, hospitalizations and emergency visits due to exacerbations as well as in improving patients’ quality of life (QoL) [1–3].

Sport Horses with Inflammatory Airway Disease (IAD) with Predominantly Eosinophils or Mast Cells Are More Predisposed to Poor Performance, Exercise Induced Pulmonary Haemorrhage (EIPH) and Have Shorter Careers When Compared to Horses with Neutrophilic IAD

Reasons for performing studyClinical differences and variable response to therapy had been suspected between sport horses with predominantly eosinophils and/or mast cells in the bronchoalveolar lavage fluid (BALF) and horses with predominantly neutrophilia in the BALF.ObjectivesTo examine possible differences in performance, response to treatment and prognosis between both groups.Study designRetrospective clinical study.MethodsA total of 174 client‐owned sport horses that were presented to the Wolvega Equine Clinic for respiratory problems between 2008 and 2013 were included. A questionnaire was used for follow‐up at least 3 months after diagnosis. Cytological BALF counts were considered increased when: neutrophils &gt;5%; eosinophils &gt;1% and mast cells &gt;2%. Data were analysed using SPSS software and Chi square tests.ResultsCough and highest mucus scores were significantly more associated with neutrophilic IAD (P = 0.009 and P = 0.007). The neutrophilia group was also significantly more responsive to therapy, often including corticosteroid inhalation, and management optimisation (P = 0.001) and had better long‐term prognosis when compared to horses from the eosinophilic or mast cell groups (P&lt;0.001). Lowest tracheal mucus scores were reported for the eosinophilic group, followed by the mast cell group. Haemosiderophage scores were significantly higher in the eosinophilic and mast cell groups (P&lt;0.001). Poor performance was reported significantly more frequently in horses with eosinophils and mast cells as the main inflammatory cell population in their BALF (P = 0.001).ConclusionsInflammatory airway disease with predominantly mast cells or eosinophils is associated with low endoscopic tracheal mucus scores. These horses are more predisposed to EIPH, poor performance and responded unfavourably to therapy when compared to horses with neutrophilic IAD.Ethical animal research: Ethical committee oversight not currently required by this congress: retrospective study of clinical records. Explicit owner informed consent for participation in this study was not stated. Sources of funding: Not stated. Competing interests: None.

Correlation between levels of exhaled hydrogen sulfide and airway inflammatory phenotype in patients with chronic persistent asthma.

Endogenous hydrogen sulfide (H2 S) may be a biomarker of asthma severity and activity. However, the relationship between exhaled H2 S and airway inflammation phenotypes in asthma remains unclear. This study examined associations between endogenous H2 S and chronic airway inflammatory phenotypes in patients with chronic persistent asthma. One hundred forty-eight patients (47 males, 101 females, 47.4 ± 15.3 years old) with chronic persistent asthma were enrolled. Induced sputum cells were examined, and patients were grouped according to sputum inflammatory cell composition. Baseline demographics, Asthma Control Test (ACT) scores, spirometry data and H₂S levels in exhaled air and plasma were obtained for all patients. The eosinophilic, neutrophilic, mixed granulocytic and paucigranulocytic inflammation groups included 57 (38.5%), 28 (18.9%), 23 (15.5%) and 40 (27%) subjects, respectively. The paucigranulocytic group had the best lung function, and patients with eosinophilic inflammation had lower ACT scores than patients with paucigranulocytic findings. In the eosinophilic group, lower exhaled H₂S were found and exhaled H2 S levels were negatively correlated with sputum eosinophil counts (R = -0.428, P < 0.01). Exhaled H2 S levels were positively correlated with percent of predicted forced expiratory volume in 1 s (R = 0.567, P < 0.01) and ACT score (R = 0.519, P < 0.01). Exhaled H2 S may be a useful marker of airway inflammation in asthma.

Biological monitoring of particulate matter accumulated in the lungs of urban asthmatic children in the Tel-Aviv area.

Lung inflammation from exposure to airborne particulate matter (PM) may be responsible for morbidity in asthma, but several studies using environmental monitoring data showed inconsistent results. Thus, the aim of this study was to evaluate the capability of induced sputum (IS) technology in order to biologically monitor PM in the lungs of urban asthmatic children. We collected clinical, demographic, biological and environmental monitoring data on 136 children referred for asthma evaluations. The study participants were divided into two groups according to IS eosinophil counts of <3% (non-eosinophilic inflammation, n = 52) and ≥3% (eosinophilic inflammation, n = 84). The eosinophilic group displays significantly higher levels of fractional exhaled nitric oxide than the non-eosinophilic one (58.8 ± 47.5 vs 28.9 ± 34.2 ppm, p = 0.007). Particles (0-2.5 and 0-5 µm) comprised a strong risk factor for eosinophilic inflammation in IS (≥3%). Children with >80% of particles (0-2.5 µm) out of the total PM accumulated in the airways displayed the highest OR 10.7 (CI 2.052-56.4 p = 0.005) for an existing eosinophilic inflammation. Heme oxygenase-1 (HO-1) enzyme levels in IS positively correlated with % eosinophils and with particles in IS ranging between 2 and 3 μm. The level of HO-1 enzyme activity and FEV1/FVC in children with <3% eosinophils, but not ≥3%, was positively and significantly correlated, showing a protective effect of HO-1. Accumulation of PM involves oxidative stress pathways and is a risk factor for developing eosinophilic inflammation in asthmatic children. IS can biologically monitor this process.

Comparison of Toxocariasis Frequency in Hyper- eosinophilic and Non- Eosinophilic Individuals Referred to Abadan Health Centers

Background: Toxocariasis is a zoonotic helminthic infection of humans and animals caused by the larvae of intestinal parasites of dogs and cats (Toxocara canis and Toxocara cati, respectively). These nematodes develop in to their adult stage in the intestines of cats and dogs. Three clinical entities have been recognized in humans; visceral larva migrans, ocular larva migrans and covert toxocariasis. Eosinophilia is a common finding in infected patients Objectives: In this study the frequency of toxocariasis in eosinophilic and non-eosinophilic individuals referred to the laboratory of Abadan health centers was compared. Materials and Methods: Serum samples were collected from individuals attending the laboratory of health centers for any medical problem and were tested for complet blood count (CBC). The samples of patients were divided in to two groups, those with more than 10% peripheral eosinophils, as the eosinophilic group (n = 54) and those with normal eosinophils (0-3%) as the non-eosinophilic group (n = 54). Samples were examined for anti-oxocara IgG by the enzyme linked immunosorbent assay (ELISA) and confirmed western blotting. Results: Anti-oxocara IgG was detected in the sera of six (11.11%) cases from the eosinophilic group and two (3.7%) of the non-eosinophilic group by the ELISA method, but all had negative results for the western blot analysis. Conclusions: The results of this study indicated that the eosinophilic individuals might beexposed to other helminthic infections or allergic agents. Further studies are required with more samples with different ages and occupations.

Defining phenotypes in asthma: a step towards personalized medicine.

Asthma is a common disease with a complex pathophysiology. It can present in various clinical forms and with different levels of severity. Unbiased cluster analytic methods have unravelled several phenotypes in cohorts representative of the whole spectrum of severity. Clusters of severe asthma include those on high-dose corticosteroid treatment, often with both inhaled and oral treatment, usually associated with severe airflow obstruction. Phenotypes with concordance between symptoms and sputum eosinophilia have been reported, including an eosinophilic inflammation-predominant group with few symptoms and late-onset disease who have a high prevalence of rhinosinusitis, aspirin sensitivity, and exacerbations. Sputum eosinophilia is also a biomarker that can predict therapeutic responses to antibody-based treatments to block the effects of the T-helper (Th)-2 cytokine, interleukin (IL)-5. Low Th2-expression has been predictive of poor therapeutic response to inhaled corticosteroid therapy. Current asthma schedules emphasise a step-up approach to treating asthma in relation to increasing severity, but, in more severe disease, phenotyping or endotyping of asthma will be necessary to determine new treatment strategies as severe asthma is recognized as being a particularly heterogeneous disease. Much less is known about 'non-eosinophilic' asthma. Phenotypic characterisation of corticosteroid insensitivity and chronic airflow obstruction of severe asthma is also needed. Phenotype-driven treatment of asthma will be further boosted by the advent of transcriptomic and proteomic technologies, with the application of systems biology or medicine approaches to defining phenotypes and biomarkers of disease and therapeutic response. This will pave the way towards personalized medicine and healthcare for asthma.

Mucosal cytokine profiles in paediatric eosinophilic oesophagitis: A case-control study

Eosinophilic oesophagitis is an inflammatory condition characterized by a dense eosinophilic infiltrate. The migration of eosinophils into the oesophagus is influenced by cytokines such as IL-5, IL-13 and eotaxin-3. The aim of this study was to evaluate changes in the cytokine expression profiles (IL-5, IL-13 and eotaxin-3/CCL26) in children after topical steroid treatment. a prospective case-control study was performed in 23 paediatric patients (age 5-16 years) with a histological diagnosis of eosinophilic oesophagitis. Histological evaluation and cytokine levels assay (IL-5, IL-13 and eotaxin-3/CCL26) in the proximal and distal oesophagus were performed before, and after 8 weeks of topical budesonide. Data were compared with a matched healthy control group. quantitative expression levels of IL-5, IL-13 and eotaxin-3 were significantly higher in the eosinophilic oesophagitis group both compared to healthy subjects (p<0.0001). A significant reduction of the eosinophil infiltrate as well as of IL-5, IL-13 and eotaxin-3 mucosal profiles was observed after steroid treatment both at the proximal and distal oesophagus (p<0.0001). IL-5, IL-13 and eotaxin-3/CCL26 are significantly over-expressed in the oesophageal epithelium of children with eosinophilic oesophagitis. Topical steroid treatment (inhaled and swallowed budesonide) can induce clinical response with partial mucosal remission.

The relationship between eosinophilia and airway remodelling in mild asthma

Eosinophilia is a marker of corticosteroid responsiveness and risk of exacerbation in asthma; although it has been linked to submucosal matrix deposition, its relationship with other features of airway remodelling is less clear. The aim of this study was to investigate the relationship between airway eosinophilia and airway remodelling. Bronchial biopsies from subjects (n=20 in each group) with mild steroid-naïve asthma, with either low (0-0.45mm(-2)) ) or high submucosal eosinophil (23.43-46.28mm(-2) ) counts and healthy controls were assessed for in vivo epithelial damage (using epidermal growth factor receptor staining), mucin expression, airway smooth muscle (ASM) hypertrophy and inflammatory cells within ASM. The proportion of in vivo damaged epithelium was significantly greater (P=0.02) in the high-eosinophil (27.37%) than the low-eosinophil (4.14%) group. Mucin expression and goblet cell numbers were similar in the two eosinophil groups; however, MUC-2 expression was increased (P=0.002) in the high-eosinophil group compared with controls. The proportion of submucosa occupied by ASM was higher in both asthma groups (P=0.021 and P=0.046) compared with controls. In the ASM, eosinophil and T-lymphocyte numbers were higher (P<0.05) in the high-eosinophil group than both the low-eosinophil group and the controls, whereas the numbers of mast cells were increased in the high-eosinophil group (P=0.01) compared with controls. Submucosal eosinophilia is a marker (and possibly a cause) of epithelial damage and is related to infiltration of ASM with eosinophils and T lymphocytes, but is unrelated to mucus metaplasia or smooth muscle hypertrophy.

Multiplex analyses of cytokine and chemokine release from the cultured fibroblast of nasal polyps: the effect of IL-17A

Conclusion: Our results demonstrate for the first time a potentially enhanced basal secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-17A-stimulated secretion of IL-6 from nasal polyp fibroblasts, enhanced basal secretion of IL-6 from eosinophilic nasal polyp fibroblasts, and a remarkable up-regulation of IL-9 and granulocyte colony-stimulating factor (G-CSF) from nasal fibroblasts by IL-17A stimulation. Objectives: The fibroblast, one of the main cell types making up nasal polyps, is thought to be a target cell of various cytokines. Methods: Subcultured fibroblasts were established from human polyp biopsy tissues. Simultaneous quantification of 27 kinds of cytokines and chemokines in culture supernatants in unstimulated and IL-17A-stimulated conditions was performed with a human multiplex cytokine assay system. Results: The IL-17A receptor was expressed at similar levels in all three groups. In the eosinophilic group, basal secretion levels of IL-6 were significantly higher than those in the control and non-eosinophilic groups. Basal secretion of MCP-1 in both the non-eosinophilic and eosinophilic groups was also higher than that of the control group. Both IL-9 and G-CSF secretion were remarkably enhanced by IL-17A stimulation in all three groups. The receptor-mediated response by IL-17A significantly up-regulated IL-6 release alone in the non-eosinophilic and eosinophilic groups as compared with the control group.

Reduction in Superoxide Dismutase Expression in the Epithelial Mucosa of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

Background: Eosinophils generate large amounts of oxidant species. The eosinophil-dominant type of chronic rhinosinusitis (CRS) with nasal polyps is related to more extensive disease and a decreased likelihood of surgical success. Superoxide dismutase (SOD) is the first-line and only antioxidant enzyme that converts superoxide to hydrogen peroxide. Methods: The patients with CRS with nasal polyps were divided into eosinophilic and noneosinophilic groups. The expression of three isoforms of SOD, intracellular copper-zinc SOD (CuZnSOD), mitochondrial manganese SOD (MnSOD) and extracellular SOD (ECSOD), were examined by enzyme activity assay, immunohistochemistry and quantitative real-time RT-PCR sampled by laser capture microdissection. Results: SOD activity in the eosinophilic and noneosinophilic groups was significantly reduced compared to that of the control groups. Immunostaining of both CuZnSOD and MnSOD in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. CuZnSOD mRNA of the eosinophilic group was significantly decreased compared with that of the control group, whereas MnSOD mRNA in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. Neither immunoreactivity nor mRNA of ECSOD was different among the three groups. The degree of epithelial damage and disease severity were inversely correlated with CuZnSOD and MnSOD immunoreactivity. Conclusions: The reduction in SOD activity and the downregulation of the SOD message are suggested to be related to eosinophil recruitment and epithelial damage of CRS with nasal polyps.