Peripheral Blood Eosinophil Count Research Articles

Peripheral Blood Eosinophil Count as a Marker of Pulmonary Allograft Rejection

Purpose Non-invasive methods for early diagnosis of acute cellular rejection (ACR) are needed. Previous studies of other solid organ transplanted recipients have shown a relationship between the eosinophil count in peripheral blood (EOSp) and the presence of ACR. However, the relationship between this biomarker and ACR in lung transplant patients remains unclear.Objective: To asses the relationship between EOSp and the presence of allograft rejection in lung transplant recipients. Methods A retrospective clinical review of 363 transbronchial biopsies (BTB) performed in 194 lung transplant patients between 2014 and 2018. We analyzed: age, date of transplant, the presence and degree of ACR, and the simultaneous absolute number of EOSp. BTB indications were classified as: 1. Protocol BTB in the first month after transplant and after ACR treatment. 2. Decrease of lung function. 3. Other indications The relationship between the EOSp count and ACR was analyzed by the Chi-square test . We calculated the sensitivity, specificity of the EOSp count to diagnose ACR. The precision of the EOS count to predict ACR was analyzed using a receiver operating characteristic ROC curve. Results BTB showed ACR in 117 of 363 cases (32.2%). The most frequent ACR degree was A2 (53%). The EOSp count in patients with ACR was higher than non-ACR patients (197 vs. 92.7; p 197 EOSp was 91% and the area under the ROC curve was 0.724 with 95% confidence interval (CI) 0.636-0.813. Conclusion The monitoring of the EOSp count can be useful to increase the diagnostic yield for ACR of BTB performed by protocol or lung function deterioration.

The Reliability of Adjusting Stepped Care Based on FeNO Monitoring for Patients with Chronic Persistent Asthma.

ObjectiveTo examine the feasibility of fractional exhaled nitrous oxide (FeNO) guided stepped care in patients with chronic persistent asthma.Methods160 patients with asthma were enrolled and randomly divided into study and control groups, and were given standardized treatment according to GINA 2014. All patients were evaluated every 3 months and their medication was adjusted according to the results of evaluation. The control group was adjusted according to the recommended protocol from GINA, while the study group was adjusted on the basis of the control group and combined with the results of FeNO. The complete control rate, failure rate of stepwise treatment, ACQ score, lung function, and peripheral blood eosinophil count were compared between the two groups.ResultsIn both study and control groups, the patient condition was effectively controlled. Strikingly, the failure rate of step therapy in study group was lower than that of control group (P<0.05), although there were no significant differences between the two groups on total control rate, ACQ score, lung function, and peripheral blood eosinophil count (P>0.05). Furthermore, the levels of FeNO positively correlated with ACQ scores and eosinophil counts or negatively with lung function.ConclusionsThe dynamic monitoring of FeNO could effectively guide the medication and reduce the rate of treatment failure, which could be used to inform standardized management of asthma.

Remotely Monitored Therapy and Nitric Oxide Suppression Identifies Nonadherence in Severe Asthma.

Poor adherence is common in difficult-to-control asthma. Distinguishing patients with difficult-to-control asthma who respond to inhaled corticosteroids (ICS) from refractory asthma is an important clinical challenge. Suppression of fractional exhaled nitric oxide (FeNO) with directly observed ICS therapy over 7 days can identify nonadherence to ICS treatment in difficult-to-control asthma. We examined the feasibility and utility of FeNO suppression testing in routine clinical care within UK severe asthma centers using remote monitoring technologies. A web-based interface with integrated remote monitoring technology was developed to deliver FeNO suppression testing. We examined the utility of FeNO suppression testing to demonstrate ICS responsiveness and clinical benefit on electronically monitored treatment with standard high-dose ICS and long-acting β2-agonist treatment. Clinical response was assessed using the Asthma Control Questionnaire-5, spirometry, and biomarker measurements (FeNO and peripheral blood eosinophil count). Of 250 subjects, 201 completed the test with 130 positive suppression tests. Compared with a negative suppression test, a positive test identified a FeNO-low population when adherent with ICS/long-acting β2-agonist (median, 26 ppb [interquartile range, 16-36 ppb] vs. 43 ppb [interquartile range, 38-73 ppb]) with significantly greater FEV1% (mean, 88.2 ± 16.4 vs. 74.1 ± 20.9; P < 0.01). Asthma Control Questionnaire-5 improved significantly in both groups (positive test: mean difference, -1.2; 95% confidence interval, -0.9 to -1.5; negative test: mean difference, -0.9; 95% confidence interval, -0.4 to -1.3). Remote FeNO suppression testing is an effective means of identifying nonadherence to ICS in subjects with difficult-to-control asthma and the substantial population of subjects who derive important clinical benefits from optimized ICS/long-acting β2-agonist treatment.

Relevance of peripheral eosinophilia in chronic pancreatitis

Background: Eosinophilia in peripheral blood has been observed in few patients with chronic pancreatitis (CP) but the clinical significance and the causes are not well understood. The aim was to analyse the features of CP in patients with and without eosinophilia and compare both groups and assess its significance.Methods: All patients diagnosed to have CP during period June 2009 to July 2012 were included in the study. Patients were divided into two groups based on eosinophil count in peripheral blood. Those with eosinophil count &gt;0.6x109/L (6%) were considered as having eosinophilia. Author had analyzed and compared the clinical features of CP in patients with and without eosinophilia.Results: There were 28 (24.56%) patients with eosinophilia among 114 CP patients. Mean age at presentation was similar in two groups. The male to female ratio was significantly higher in patients with eosinophilia (p=0.03). Patients with eosinophilia had higher incidence of pancreas enlargement (78.57% vs. 37.2%, p=0.007). Mean intraductal pressures (20.42 vs. 22.52; p=0.05) and average pancreatic ductal diameter (7.85 vs. 8.90; p=0.03) were lower in patients with eosinophilia. The incidence of complications was significantly more in patients with eosinophilia (85.71% vs. 20.93%; p=&lt;0.001). There was no infiltration of eosinophils in all the pancreatic tissue samples analysed in both groups.Conclusions: Association of eosinophilia with CP is a relatively common entity. It is associated with significantly increased incidence of disease related inflammatory complications, but the exact mechanism is not clear. Whether eosinophilia is a cause or effect of complication is not clear.

A sputum 6-gene signature predicts future exacerbations of poorly controlled asthma

Improved diagnostic tools for predicting future exacerbation frequency in asthmatic patients are required. Asputum gene expression signature of 6 biomarkers (6-gene signature [6GS], including Charcot-Leyden crystal galectin [CLC]; carboxypeptidase 3 [CPA3]; deoxyribonuclease 1-like 3 [DNASE1L3]; alkaline phosphatase, liver/bone/kidney [ALPL]; CXCR2; and IL1B) predicts inflammatory and treatment response phenotypes in patients with stable asthma. Recently, we demonstrated that azithromycin (AZM) add-on treatment in patients with uncontrolled moderate-to-severe asthma significantly reduced asthma exacerbations (AMAZES clinical trial). We sought to test whether the 6GS predicts future exacerbation and inflammatory phenotypes in a subpopulation of AMAZES and to test the effect of AZM therapy on 6GS expression and prognostic capacity. One hundred forty-two patients (73 placebo-treated and 69 AZM-treated patients) had sputum stored for quantitative PCR of 6GS markers at baseline and after 48weeks of treatment. Logistic regression and receiver operating characteristic and area under the curve (AUC) determination were performed on baseline measures, and in an exploratory analysis the predictive value of the 6GS was compared with conventional biomarkers for exacerbation and inflammatory phenotypes. The 6GS significantly predicted all future exacerbation phenotypes tested. Calculated AUCs for the 6GS were significantly greater than AUCs for peripheral blood eosinophil counts, sputum neutrophil counts, and combined sputum eosinophil and neutrophil counts. 6GS AUCs were also numerically but not significantly greater than those for fractional exhaled nitric oxide values and sputum eosinophil counts. AZM treatment altered neither 6GS expression nor the predictive capacity of the 6GS for future exacerbation phenotypes. The 6GS was a significant predictor of airway inflammatory phenotype in this population. We demonstrate that a sputum gene signature can predict future exacerbation phenotypes of asthma, with the greatest biomarker performance in identifying those who would experience frequent severe exacerbations. AZM therapy did not modify 6GS expression or biomarker performance, suggesting the therapeutic action of AZM is independent of 6GS-related inflammatory pathways.

Lund-Mackay Computed Tomography Score Is Associated With Obstructive Pulmonary Function Changes in Chronic Cough Patients.

A remarkable relationship between upper airway conditions and lung diseases has been reported. At the same time, sinonasal findings in chronic cough patients have not been fully examined. The purpose of this study is to show paranasal sinus findings and lung function in chronic cough patients without asthma and chest X-ray abnormalities. A total of 1412 patients with persistent cough were enrolled in this study. Of these patients, 376 patients were evaluated for further examination, as the patients with asthma and/or chest X-ray abnormality were excluded from the study. Normal control subjects without any chronic respiratory symptoms were also recruited. Pulmonary function was examined by spirometry. A bronchial obstruction reversibility test was applied. The Lund-Mackay computed tomography (CT) score, peripheral blood eosinophil count, and immunoglobulin E concentration in serum samples were examined. The Sino-Nasal Outcome Test was used to determine the severity of clinical symptoms. The patients with an abnormal soft tissue shadow in the paranasal sinus had significant obstructive lung function. The percent predicted forced expiratory volume in 1 second (FEV1.0) and the FEV1.0/forced vital capacity ratio negatively correlated with Lund-Mackay CT scores both before and after bronchodilator inhalation. There was a statistically significant correlation between pulmonary function and eosinophil count. The patients with chronic cough frequently had paranasal sinus abnormalities. The Lund-Mackay CT score may be useful for assessing the condition of the lower airway in chronic cough patients. Upper airway examinations should play a part in the management of chronic cough.

Efficacy of Sublingual Administration of Dermatophagoides Farinae Drops for Treatment of Pediatric Allergic Rhinitis Accompanied by Adenoid Hypertrophy and Improvement of Immune Function.

BackgroundThe aim of this study was to determine the efficacy of sublingual administration of Dermatophagoides farinae drops for the treatment of allergic rhinitis (AR) accompanied by adenoid hypertrophy and the effect on immune function in children.Material/MethodsEosinophil counts in peripheral blood before and after treatment were determined; serum levels of immunoglobulin E (IgE), total IgE (T-IgE), immunoglobulin G4 (IgG4), interleukin-2 (IL-2), and interleukin-6 (IL-6) before and after treatment were detected by enzyme-linked immunosorbent assay.ResultsThe total effective rate in the study group was significantly higher than that in the control group (P<0.05). In both the study and control groups, symptom scores, medication scores, eosinophil counts in the peripheral blood, and serum levels of IgE, T-IgE, and IL-6 were significantly lower than those before treatment (P<0.05), while the serum levels of IgG4 and IL-2 were significantly higher than those before treatment (P<0.05). After treatment, symptom scores, medication scores, eosinophil counts in the peripheral blood, and serum levels of IgE, T-IgE, and IL-6 in the study group were significantly lower than those in the control group (P<0.05), while the serum levels of IgG4 and IL-2 were significantly higher in the study group than those in the control group (P<0.05).ConclusionsSublingual administration of D. farinae drops improved the clinical symptoms of pediatric AR caused by Dermatophagoides mites and improved the immune functions in children.

Using the Peripheral Blood Eosinophil Count to Manage Patients with Chronic Obstructive Pulmonary Disease.

Using the Peripheral Blood Eosinophil Count to Manage Patients with Chronic Obstructive Pulmonary Disease.

The assessment value of peripheral blood eosinophils for treatment prognosis of chronic rhinosinusitis

Objective:The purposes of present study were to explore the relative factors affecting treatment outcomes of chronic rhinosinusitis(CRS),and investigated the clinical manifestation changes of CRS patients after post-operative treatment of oral glucocorticoid. Method: Forty-eight CRS subjects including 14 illness un-controlled group, and 34 illness controlled group were enrolled, and peripheral blood leukocytes, eosinophils, neutrophils, mononuclear cells, lymphocytes were detected and clinical features comprised of VAS, endoscopy and CT scan scores were recorded; 20 days'oral glucocorticoid was prescribed to the patients in illness un-controlled group and the data described above were analyzed. Result:Compared to illness controlled group, illness uncontrolled subjects had higher peripheral blood eosinophils count(P=0.028), and complicated with higher rate of allergic rhinitis(P=0.035), asthma(P=0.024), atopy patients(P=0.042); the eosinophils was positively correlated with total VAS scores(R=0,410, P=0,007); the eosinophils count(P=0.007), total VAS scores(P<0.001), total endoscopy scores(P=0.001) were significant decreased after oral glucocorticoid treatment. Conclusion: Allergic rhinitis, asthma, atopy, and elevated eosinophils counts were risk factors of the prognosis of CRS, oral glucocorticoid treatment showed additional benefit to the illness un-controlled CRS subjects, and blood eosinophils count was an important predictive factor for clinical manifestation of CRS.

Etiologies and differential markers of eosinophilia-associated diseases in the Allergy Department of a single university hospital

Purpose: We aimed to analyze the frequency of eosinophilia-associated diseases and to search for possible markers that may be useful for their differential diagnosis. Methods: We retrospectively reviewed the medical records of 148 patients with peripheral blood eosinophil count of more than 500/μL who visited the Allergy Department of Chonnam National University Hospital for the first time from January to December 2016. Blood eosinophilia was categorized as mild ( 5,000/μL). Results: Blood eosinophilia was mostly caused by allergic diseases (41.9%), parasitic infestation (23.6%), and drug allergy (19.6%). Eosinophil count was higher in patients with parasitic infestation (P<0.01), drug allergy (P<0.01), hypereosinophilic syndrome (HES, P<0.001), or eosinophilic granulomatosis with polyangiitis (EGPA, P<0.001) than in those with allergic diseases. The eosinophilic cationic protein level was higher in patients with HES than in those with allergic diseases (P<0.05) and parasitic infestation (P<0.05). The total IgE level was lower in patients with HES than in those with parasitic infestation (P<0.05) and EGPA (P<0.05). The vitamin B12 level was higher in patients with HES than in those with parasitic infestation (P<0.05). There was no statistically significant differ ence in tryptase levels between the groups. The most common cause of mild eosinophilia was allergic diseases (59.8%), followed by parasitic infestation (22.7%) and drug allergy (13.4%). The common causes of moderate eosinophilia were drug allergy (37.8%), par asitic infestation (29.7%), and allergic diseases (10.8%). The common causes of severe eosinophilia were EGPA (28.6%), HES (21.4%), parasitic infestation (14.3%), and drug allergy (14.3%). Conclusion: Common causes of blood eosinophilia in patients who visit the allergy department are allergic diseases, parasitic infes tation, and drug allergy. Several markers, including eosinophil count, total IgE, and vitamin B12, may be useful for the differential di agnosis of eosinophilia-associated diseases. (Allergy Asthma Respir Dis 2019;7:142-149)

Blood eosinophils may predict radiographic sinus opacification in patients with chronic rhinitis.

The association between chronic rhinosinusitis (CRS) and chronic rhinitis remains unclear. The aim of this study was to estimate the predictive factors for sinus opacification in chronic rhinitis patients without obvious CRS. We retrospectively studied a total of 332 adult patients with chronic rhinitis who visited our clinic from January 2015 to December 2017. All of the patients underwent endoscopic examination, allergy test, and osteomeatal-unit computed tomography. The subjects were assigned to the normal sinus (NS) group (Lund-Mackay score [LMS] <5) and sinus opacification (SO) group (LMS ≥5). A total of 288 patients were eligible for this study. Of them, 183 (63.5%) were classified in the NS group and 105 (36.5%) in the SO group. Total immunoglobulin E (IgE) level and peripheral blood eosinophil count were significantly higher in the SO than NS group (p = 0.031 and p < 0.0001, respectively). Using Pearson correlation coefficients, we determined that eosinophil count had a positive correlation with the LMS (r = 0.282). In logistic analysis, the interquartile range increase (0.19 × 109 /L) of the eosinophil count was significantly associated with SO (odds ratio [OR] 1.76; 95% confidence interval [CI], 1.30 to 2.39). After adjusting for age, gender, smoking, drinking, and underlying disease, the interquartile range increase of the eosinophil count increased the odds of SO to 1.69-fold; this increase was statistically significant (p = 0.007; 95% CI, 1.17 to 2.43). Peripheral blood eosinophil count is an independent predictor of CRS in patients with chronic rhinitis.

A Zebrafish JAK1-A634D Gain-of-Function Model Provides New Insights into the Pathogenesis of Familial Hypereosinophilia

Introduction: JAK/STAT signaling is of major importance for hematopoiesis and immune function. A heterozygous JAK1 c.1901C>A de novo point mutation was identified in three members of a family (a mother and two male sons). These patients presented with a unique clinical phenotype of severe atopic dermatitis, markedly elevated peripheral blood eosinophil counts with eosinophilic infiltration of the liver and gastrointestinal tract, hepatosplenomegaly, and failure to thrive. Treatment with ruxolitinib, a JAK1/2 inhibitor, resulted in reduced eosinophilia and improved growth (Del Bel et al. JACI 2017). However, the role of this JAK1 mutation in hematopoiesis remains unclear.Methods: ubi-JAK1-WT or A634D-P2A-sfGFP-pA zebrafish transgenic lines were generated incorporating the human genes. Both of these constructs were injected into embryos, but the survival rate for the JAK1-A634D embryos was very low. Six hour post-fertilization (hpf) embryos expressing the mutant transgene were treated with 1 µM ruxolitinib for 24h, which dramatically increased survival. Whole-mount in situ hybridization (WISH) was used to assess changes in hematopoietic stem cells/blood cell populations due to wild-type or JAK1-A634D expression at 24, 28, 36 and 48 hpf using a battery of blood lineage specific probes. O-dianisidine staining was employed to evaluate hemoglobin levels. ImageJ cell counter pluggin was used for cell quantification. Gata1 and o-dianisidine staining intensity was analyzed using Ilastik and CellProfiler. Six groups of 30-50 embryos were analyzed by RNA sequencing (RNAseq): control, JAK1-WT and JAK1-A634D at 28 and 36 hpf. RNA was extracted using Trizol. RNAseq data was analyzed with edgeR and enrichment analysis was performed using DAVID 6.8.Results: JAK1-A634D was toxic to zebrafish embryos but they survived to sexual maturity post-ruxolitinib therapy. F1 embryos from JAK1-A634D founders with high expression of the transgene exhibited abnormal development (70% of embryos) which could be reduced to 12% of embryos following 24h exposure to 1 µM ruxolitinib. This rescue suggests that JAK1-A634D is highly active in zebrafish and its activity needs to be under tight regulation for normal development. Both JAK1-WT and A634D mutant fish demonstrated increased HSPCs (c-myb/runx1 expression) at 36 hpf (p<0.0001) through 48 hpf (A634D>WT>controls; p=0.0308 and p=0.0045, respectively). pu.1/spi1 early myeloid expression showed a similar expression pattern at 28 hpf, A634D>WT>controls; p<0.0001 for both). At 24 and 28 hpf, granulocytes expressing myeloperoxidase (mpx) were increased in both JAK1-WT and JAK1-A634D mutants, but particularly high in JAK1-A634D embryos at 48 hpf (p<0.0001). Macrophages marked by l-plastin (lcp) expression, showed similar cell numbers in JAK1-WT and controls at 24 and 28 hpf, but a significant decrease in JAK1-A634D embryos (p<0.0001). An increase of carboxypeptidase A5 positive mast cells was observed in both JAK1-WT and JAK1-A634D embryos at 48 hpf compared with controls (p<0.0001). We observed an increase of gata1a expression at 24 hpf in A634D embryos (p=0.0058, p=0.0065), but o-dianisidine staining at 48 hpf revealed a decrease in hemoglobin in both JAK1 lines (p<0.0001). The latter data is supported by RNAseq results revealing decreased expression of hemoglobin-associated genes at 36 hpf in both transgenic lines. RNAseq revealed a total of 365 genes differentially expressed, with enrichment for genes coding for proteosomal and ribosomal proteins. In the JAK-1WT we found 79 genes upregulated and 115 downregulated; in the JAK1-A634D, 94 genes were upregulated and 77 were downregulated. JAK-STAT pathway genes were upregulated in the A634D mutant (p<0.05), as well as a trend for genes associated with hematopoiesis (p=0.0633) and negative regulation of cell proliferation (p=0.0658).Conclusions: JAK1-A634D plays an important role in zebrafish development and specifically impacts the myeloid lineage, particularly the granulocyte branch, from which eosinophils arise. Ruxolitinib can revert the arrested development phenotype, demonstrating the specificity of this targeted therapy. Our model provides the first in vivo evidence of the effects of the JAK1-A634D mutation on hematopoiesis and will provide further insight in understanding the cause of familial hypereosinophilia. DisclosuresNo relevant conflicts of interest to declare.

The characterization of asthma with blood eosinophilia in adults in Latin America

Objective: To identify and characterize asthma with blood eosinophilia in adults. Methods: This cross-sectional study consisted of 164 asthma patients, aged 18 years or older. Multivariate analyses by logistic regression were performed to identify clinical characteristics and biomarkers associated with asthma with blood eosinophilia (defined as asthma and a peripheral blood eosinophil count ≥400 cells/mm3). To evaluate the diagnostic accuracy of these biomarkers, the sensitivity, specificity and predictive values were calculated. Additionally, the area under the receiver operating characteristic (ROC) curve (AUC) was estimated for each biomarker. Results: Overall, 37.8% (95%CI: 30.7–45.4%) of asthma patients had blood eosinophilia. The following factors were associated with this characteristic: patient age <50 years (OR 3.25; 95% CI: 1.33–7.94), a serum level of IgE ≥300 UI/mL (OR 2.32; 95%CI: 1.14–4.75), and an Asthma Control Test (ACT) score <20 points (OR 3.10; 95%CI: 1.35–4.75); asthma with blood eosinophilia was also associated with a baseline FEV1/FVC <70% (OR 2.68; 95%CI: 1.28–5.59). On the other hand, age <50 years and ACT score <20 showed the highest sensitivity (above 80% each). Serum IgE level ≥300 UI/mL had the highest specificity (almost 68%). Finally, those with an ACT score <20 had the highest AUC (68%). Conclusions: In our study population, one-third of asthmatic adults had asthma with blood eosinophilia. Furthermore, the prevalence was greater in those ≤50 years of age; these patients experienced more severe, more poorly controlled asthma and had higher total serum IgE levels.

PERIPHERAL BLOOD EOSINOPHIL SHIFTS IN SEVERE, UNCONTROLLED ASTHMA

Introduction Greater clarity is needed on peripheral blood eosinophil counts (BEC) associated with events such as exacerbations or responsiveness to biologics in severe asthma. Inclusion criteria and prespecified analyses on peripheral BECs vary between clinical trials. Stability of BEC on repeated measures in this population is unknown. We examined shifts in BEC in patients with severe, uncontrolled asthma despite high-dosage inhaled corticosteroids/long-acting β2-agonists. Methods BEC shift was examined in patients randomized to placebo in two Phase III studies, SIROCCO (NCT01928771; 48 weeks) and CALIMA (NCT01914757; 56 weeks). We grouped patients by baseline BEC and counted the number in each baseline group who had ≥1 recorded peripheral BEC and who then shifted BEC group during the trial. Results 141 patients receiving placebo had a baseline peripheral BEC <150 cells/μL. Of these, 70.2% (n=99) had ≥1 BEC ≥150 cells/μL and 34.8% (n=49) had a BEC ≥300 cells/μL. An additional 170 patients had a baseline peripheral BEC 150≤300 cells/μL. Of these, 62.4% (n=106) had ≥1 BEC ≥300 cells/μL. 428 patients had a baseline peripheral BEC ≥300 cells/μL. Of these, 52.8% (n=226) had ≥1 BEC <300 cells/μL, and 22.4% (n=96) had a BEC <150 cells/μL (figure). Conclusions Most patients with a baseline BEC <150 cells/µL during SIROCCO or CALIMA, and approximately one-third had at least one BEC measurement ≥300 cells/µL. The data suggest that a single BEC does not negate the possibility of a patient having eosinophil-driven disease. Performing additional BECs may be of benefit. Percentage of Patients with Shifts in Peripheral Blood Eosinophil Count Group After Baseline Greater clarity is needed on peripheral blood eosinophil counts (BEC) associated with events such as exacerbations or responsiveness to biologics in severe asthma. Inclusion criteria and prespecified analyses on peripheral BECs vary between clinical trials. Stability of BEC on repeated measures in this population is unknown. We examined shifts in BEC in patients with severe, uncontrolled asthma despite high-dosage inhaled corticosteroids/long-acting β2-agonists. BEC shift was examined in patients randomized to placebo in two Phase III studies, SIROCCO (NCT01928771; 48 weeks) and CALIMA (NCT01914757; 56 weeks). We grouped patients by baseline BEC and counted the number in each baseline group who had ≥1 recorded peripheral BEC and who then shifted BEC group during the trial. 141 patients receiving placebo had a baseline peripheral BEC <150 cells/μL. Of these, 70.2% (n=99) had ≥1 BEC ≥150 cells/μL and 34.8% (n=49) had a BEC ≥300 cells/μL. An additional 170 patients had a baseline peripheral BEC 150≤300 cells/μL. Of these, 62.4% (n=106) had ≥1 BEC ≥300 cells/μL. 428 patients had a baseline peripheral BEC ≥300 cells/μL. Of these, 52.8% (n=226) had ≥1 BEC <300 cells/μL, and 22.4% (n=96) had a BEC <150 cells/μL (figure). Most patients with a baseline BEC <150 cells/µL during SIROCCO or CALIMA, and approximately one-third had at least one BEC measurement ≥300 cells/µL. The data suggest that a single BEC does not negate the possibility of a patient having eosinophil-driven disease. Performing additional BECs may be of benefit.

Urinary schistosomiasis in migrant population: a case series from a single centre in southern Italy.

To understand the frequency of urinary schistosomiasis, in migrants in clinical follow-up at the infectious disease outpatient clinic of ARNAS Civico Hospital in Palermo Italy, to raise awareness on this neglected tropical disease. A retrospective analysis of migrant patients in clinical care in our centre during the triennium 2015-2017. 2639 migrants have been in clinical care during the triennium 2015-2017, 72% are male and 28% are female. 214 patients were tested for the presence of Schistosoma eggs in urine, these patients are all male. All the patients tested, reported macroscopic haematuria and the 54% had an increase in the peripheral blood eosinophil count. Ninety subjects had a positive microscopic examination for Schistosoma haematobium eggs. Patients were treated with a standard dose of praziquantel (40mg/kg), and tested for Schistosoma 1month after the end of therapy. All the subjects fully recovered. Considering the migration phenomenon, the observation of these tropical diseases in European hospitals is becoming more and more common and an increasing number of health care professionals will be dealing with migrants. Searching for haematuria and eosinophilia and then testing for Schistosoma in this specific population will increase the number of diagnosis and correct treatment of urinary schistosomiasis, improving the patients' quality of life and preventing severe complications of the disease.

Eosinophils Target Therapy for Severe Asthma: Critical Points.

Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled” or if it remains ‘‘uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma.

Eosinophilic asthma, according to a blood eosinophil criterion, is associated with disease severity and lack of control among underprivileged urban Brazilians.

Asthma is a syndrome with multiple phenotypes. Peripheral blood eosinophil counts might be the ideal biomarker to identify subjects with eosinophilic asthma. It is available, inexpensive, and it is associated with eosinophilia in sputum. The aim of this study was to evaluate whether blood eosinophilia is associated with asthma severity and to evaluate whether blood eosinophilia is associated with lack of control of asthma symptoms and airway obstruction. Case control study. The cases were subjects recruited from a cohort of patients with severe asthma, in Salvador-BR, demanding continuous inhaled corticosteroids and LABA. There were two control groups: 1) subjects with mild/moderate asthma, 2) subjects with no asthma. Subjects enrolled in the study answered questionnaires, had their blood and stool samples collected, performed spirometry and SPT. We established a cutoff ≥ 260 cells/mm3 for blood eosinophilia. We evaluated 544 subjects in the case group, 452 subjects with mild to moderate asthma and 450 subjects with no asthma. The subjects of the case group had higher odds of presenting the eosinophilic phenotype in comparison to subjects with mild to moderate asthma [OR 1.60 95CI(1.19-2.16)] and no asthma [OR 3.93; 95CI(2.90-5.33)]. The eosinophilic phenotype, according to blood count, is associated with uncontrolled asthma [OR 1.56; 95CI(1.06-2.28)], but it is not associated with airway obstruction [OR 0.87; 95CI(0.61-1.24)]. We conclude that the blood eosinophilia is a biomarker associated with asthma severity and poor symptom control, but we found no association with reduced lung function.

Severe Asthma Phenotypes Classified by Site of Airway Involvement and Remodeling via Chest CT Scan.

This study aimed to establish a system that can classify severe asthma on the basis of airway remodeling patterns visualizedusing computed tomography (CT) images and to evaluate the clinical characteristics of individual image-based subtypes. Chest CT images from severe asthma patients were retrospectively evaluated to classify phenotypes by site of airway involvement and remodeling. The association between radiologic subtypes and clinical characteristics was assessed. Of 91 patients with severe asthma, 74 (81.3%) exhibited abnormal radiologic findings, including bronchial wall thickening (BT), mucus plugging (MP), and bronchiectasis (BE). The severity of BT and the extent of MP were independently associated with peripheral blood eosinophil count (P=.012, r2=0.112) and sputum eosinophil count (P=.022, r2=0.090), respectively. The large-to-medium airway remodeling type, which showed diffuse BT combined with MP and BE, accounted for 44% of patients and revealed higher peripheral blood eosinophil counts than other types. In the small airway remodeling type, which accounted for 6.6% of patients, we observed a higher rate of fixed airflow obstruction, along with a predominance of males and smokers and more frequent use of controller medication than other phenotypes. In 26% of patients with severe asthma, no prominent airway remodeling was observed (near-normal type); the near-normal type required oral corticosteroids less frequently than the large-to-medium airway and small airway remodeling types. Depending on the site of airway involvement and remodeling pattern, 3 different structural types can be distinguished in chest CT findings from patients with severe asthma. Remodeling in large-to-medium sized airways revealed an association with systemic eosinophilic inflammation in patients with severe asthma.

From Eosinophilic Gastroenteritis to Chronic Eosinophilic Leukemia: A Case of Hypereosinophilia

Introduction Hypereosinophilia is generally defined as a peripheral blood eosinophil count greater than 1500/mm3 and can be associated with reactive (secondary) or hematologic (primary) disorders, which can lead to end-organ damage. We present a patient with gastrointestinal symptoms in the setting of absolute eosinophilia. Work-up was initially suggestive of eosinophilic gastroenteritis, a rare inflammatory disorder characterized by eosinophilic tissue infiltration with no known natural progression to date. However, additional studies revealed a clonal genetic abnormality on chromosomal analysis in the diagnosis of chronic eosinophilic leukemia, not otherwise specified (CEL, NOS). Case Description An 82-year-old female with history of psoriatic arthritis presented with a 2-week history of watery, nonbloody bowel movements (5-20 per day) along with abdominal cramping, nausea and worsening oral intolerance. Vital signs and physical exam were unremarkable. Laboratory studies were significant for a WBC of 25,000 (40% eosinophils) and elevated IgE level at 138IU/mL. CT of the abdomen was also unremarkable.2578_A Figure 1. Duodenal biopsy, increased eosinophils infiltrating epithelium and lamina propria.2578_B Figure 2. Bone marrow biopsy, hypercellular bone marrow with eosinophilia.An esophagogastroduodenoscopy was performed, demonstrating diffuse duodenal erythema, edema and villous blunting as well as erythematous and hypertrophied gastric folds. Random duodenal, gastric, esophageal, and colonic biopsies revealed increased eosinophils (60 to >100 eos/hpf). Bone marrow biopsy was notable for hypercellularity and marked eosinophilia. The chromosomal analysis detected a clonal cytogenetic abnormality, del(11q), satisfying the 2017 WHO diagnostic criteria for CEL, NOS. The patient was treated with corticosteroids with resolution of absolute eosinophilia and gastrointestinal symptoms. Discussion This case elucidates the importance of undergoing a complete evaluation for hypereosinophilia, beginning with assessing for secondary causes, followed by thorough hematologic diagnostic studies. The localization of the patient's symptoms in the gastrointestinal tract, coupled with biopsy-proven eosinophilic infiltration, pointed initially towards eosinophilic gastroenteritis. However, the abnormal chromosomal analysis proved the diagnosis of CEL, NOS. As more cases suggestive of eosinophilic gastroenteritis emerge, the hope is to better understand the pathogenesis and natural progression of this rare disease, as well as to compare the effectiveness of therapeutic strategies with that of the hematologydriven processes.

Anti-inflammatory effects of roflumilast in chronic obstructive pulmonary disease (ROBERT): a 16-week, randomised, placebo-controlled trial

The clinical effects of roflumilast, a selective phosphodiesterase-4 inhibitor, are well established, but little is known about the anti-inflammatory mechanisms underlying the drug's efficacy. The aim of the ROflumilast Biopsy European Research Trial (ROBERT) was to assess the anti-inflammatory effects of roflumilast on bronchial mucosal inflammation in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and chronic bronchitis. ROBERT was a randomised, double-blind, placebo-controlled trial done at 18 sites in five countries. Eligible patients were aged 40-80 years, had COPD, and had had a chronic productive cough for 3 months in each of the two previous years. Patients also had to have a post-bronchodilator predicted FEV1 30-80% and a post-bronchodilator FEV1/forced vital capacity ratio of 70% or less. Patients entered a 6-week run-in period before being randomly assigned (1:1) via a computerised central randomisation system to roflumilast 500 μg once daily or placebo for 16 weeks, in addition to bronchodilator therapy (inhaled corticosteroids were not permitted). Randomisation was stratified by concomitant use of long-acting β agonist. Both participants and investigators were masked to group assignment. Roflumilast and placebo were supplied as identical yellow, triangular tablets. Airway inflammation was assessed by quantification of inflammatory cells in bronchial biopsy samples and induced sputum samples. The primary endpoint was the change in the number of CD8 inflammatory cells in bronchial biopsy submucosa from randomisation to week 16 in the intention-to-treat population. Changes in cell counts of additional inflammatory markers, including eosinophils, were assessed as secondary endpoints. This trial is registered with ClinicalTrials.gov, number NCT01509677, and is closed to new participants, with follow-up completed. Between Jan 4, 2012, and Feb 11, 2016, 158 patients were randomly assigned: 79 to the roflumilast group, and 79 to the placebo group. At week 16, the change in the number of CD8 cells in the bronchial submucosa did not differ significantly between the roflumilast and placebo groups (treatment ratio 1·03 [95% CI 0·82-1·30]; p=0·79). However, compared with placebo, roflumilast was associated with a significant reduction in eosinophils in bronchial biopsy samples at week 16 (treatment ratio 0·53 [95% CI 0·34-0·82]; p=0·0046). Significant reductions in both absolute (p=0·0042) and differential (p=0·0086) eosinophil cell counts in induced sputum were also noted with roflumilast compared with placebo, but peripheral blood eosinophil counts were not significantly affected. We noted no other significant effects of roflumilast on bronchial mucosal inflammatory cells. The most common (ie, occurring in >5% patients) moderate adverse events were worsening of COPD (three [4%] patients in the roflumilast group vs seven [9%] in the placebo group), cough (six [8%] vs four [5%]), diarrhoea (four [5%] vs three [4%]), and nasopharyngitis (three [4%] vs five [6%]). Severe adverse events included worsening of COPD, which occurred in four (5%) patients in the roflumilast group and two (3%) in the placebo group. No deaths occurred during the study. Serious adverse events occurred in eight (10%) patients in the roflumilast group and five (6%) in the placebo group. 16 weeks of treatment with roflumilast did not affect the number of CD8 cells in bronchial submucosa compared with placebo. However, we noted significant reductions in eosinophil cell counts in bronchial biopsy samples and induced sputum, generating the hypothesis that the effect of roflumilast in COPD could be mediated by an effect on lung eosinophils. Takeda and AstraZeneca.