Median Eosinophil Count Research Articles

Predictors of exacerbation in Japanese patients with severe asthma: Analysis of the severe asthma research program (Okayama-SARP) cohort

BackgroundBecause exacerbation of severe asthma decreases patients’ quality of life, this study aimed to identify predictive factors for asthma exacerbation. MethodsJapanese patients with severe asthma requiring treatment according to the Global Initiative for Asthma (GINA) guidelines ≥ Step 4 between January 2018 and August 2021 were prospectively enrolled and followed up for one year at facilities participating in the Okayama Respiratory Disease Study Group (Okayama Severe Asthma Research Program). ResultsA total of 85 patients (29 men and 56 women) were included. The median age was 64 (interquartile range [IQR], 51–72) years. Treatment according to GINA Steps 4 and 5 was required in 29 and 56 patients, respectively, and 44 patients (51.8%) were treated with biologics. The median peripheral-blood eosinophil count, fractional exhaled nitric oxide, IgE level, and percent predicted FEV1 (%FEV1) at enrollment were 204 (IQR, 49–436)/μL, 28 (IQR, 15–43) ppb, 172 (IQR, 56–473) IU/mL, and 80.0 (IQR, 61.1–96.1) %, respectively. Exacerbation during the previous year, asthma control test (ACT) score <20, %FEV1 <60%, and serum IL-10 level >6.7 pg/mL were associated with exacerbation during the observation period. ConclusionsExacerbation during the previous year, low ACT score, and low %FEV1 were predictive factors of future exacerbation, even in a cohort with >50% of patients treated with biologics. Furthermore, high serum IL-10 levels might be a new predictive factor.

Clinical Characteristics and Outcomes of CML in Adolescents and Young Adults

BackgroundWhile Chronic Myeloid Leukemia (CML) is a disease of older adults, there is a growing population of adolescent and young adults (AYAs) with CML. This study evaluated the clinical characteristics and outcomes of CML in AYAs. Patients and methodsData from medical records of adults with chronic phase CML diagnosed and treated at our center from 2011until 2021were retrospectively analyzed. Age between 18 and 29 years was used to define AYAs. Response to tyrosine kinase inhibitors (TKIs), progression to accelerated phase (AP) or blast crisis (BC), event-free survival (EFS) and overall survival (OS) were compared between AYAs and older adults. ResultsAmong 163 patients included, 41 (25.1%) were AYAs. AYAs were more likely to be males (P = .02), to present with symptoms (P = .004), had a higher median white blood cell count (P = .007), neutrophil count (P = .029), eosinophil count (P = 0.01), low-risk Sokal (P = .033) and Hasford (P = .005) groups. TKI-sensitivity as well as median times for achievement of complete cytogenetic and major molecular response were comparable between both groups. After a median follow-up of 76 (range: 11-235) months, there was no difference in OS (P = .528), or cumulative incidence of transformation to accelerated phase or blast crisis (P = .11). On the other hand, AYA had an inferior EFS (P = .034). ConclusionA quarter of the patients diagnosed with CML in our population were AYAs. Despite being characterized as “lower-risk,” they presented with a greater disease burden, had a shorter EFS but comparable OS. Further studies are needed to better understand the disease biology of this group.

A tale of two studies: is peripheral eosinophilia associated with Dientamoeba fragilis detection in adult stool samples?

The protozoan parasite Dientamoeba fragilis is a frequently isolated stool organism and postulated cause of gastrointestinal symptoms. Peripheral blood eosinophilia has been described. This is the first study amongst the Australasian adult population to assess the relationship between organism detection and eosinophilia. A case-control study took place over 7 years at a single Sydney laboratory site, evaluating patients with D.fragilis identified on stool using real-time PCR with a recent full blood count, to control groups with Giardia spp. and sequential negatives with neither organism. A nested study compared those with microscopic evidence of D.fragilis as a marker of disease burden, to molecular diagnosis alone. Sixty-four D.fragilis, 30 Giardia spp., and 94 sequential controls were enrolled. Only 60.1% of samples were preserved in sodium acetate-acetic acid formalin (SAF) fixative, indication mostly not documented. The major co-organism detected amongst all participants was Blastocystis sp., particularly in the D.fragilis cohort (37.2%). The most common pathogen amongst sequential controls was Campylobacter spp. (7.4%). Patients with D.fragilis were more likely (12.5%) to have a clinically significant eosinophilia (>0.5×109/L) compared to those with Giardia spp. (3.3%) or sequential controls (4.3%) (p=0.03). A significant difference was also noted in the overall median eosinophil count of those with D.fragilis versus all controls (0.2 vs 0.1×109/L, p=0.01); however, this was within the reference interval (where up to >0.5×109/L is accepted in healthy individuals within a typical population). No eosinophil difference was found between those with molecular versus additional microscopic detection of D.fragilis (0.1 vs 0.1×109/L). These results support an association between the identification of clinically significant peripheral blood eosinophilia and D.fragilis presence, which may impact the diagnostic approach to the patient with unexplained eosinophilia. Further prospective trials may help assess any significance further and the implication of co-carriage with other enteric organisms. The importance of clinical indication and need for appropriate fixative media in diagnostic parasitology are also highlighted.

Usefulness of Computed Tomography for Evaluating the Effects of Bronchial Thermoplasty in Japanese Patients with Severe Asthma.

Bronchial thermoplasty (BT) improves clinical outcomes and quality of life for patients with severe asthma and has shown sustained reductions in airway narrowing and air trapping in previous CT studies. However, there is a lack of a comprehensive analysis, including CT evaluation, of clinical outcomes in Japanese patients who have undergone BT for severe asthma. This study aimed to evaluate the impact of BT in Japanese asthma patients, with a focus on the CT metric "WA at Pi10" to assess airway disease. Twelve patients with severe persistent asthma who underwent BT were assessed using ACQ6, AQLQ, pulmonary function tests, FeNO measurement, blood sampling, and chest CT before BT and one year after the third procedure for the upper lobes. The median age of the patient was 62.0 years, 7/12 (58.3%) were male, 4/12 (33.3%) used regular oral corticosteroids, and 8/12 (66.7%) received biologics. Median FEV1% was 73.6%, and median peripheral eosinophil count was 163.8/μL. After one year of BT, ACQ6 scores improved from 2.4 to 0.8 points (p = 0.007), and AQLQ scores improved from 4.3 to 5.8 points (p < 0.001). Significant improvements were also observed in asthma exacerbations, unscheduled visits due to exacerbations, FeNO, and √WA at Pi10 (p < 0.05). The baseline mucus score on the CT findings was negatively correlated with FEV1 (r = -0.688, p = 0.013) and with the maximum mid-expiratory flow rate (r = -0.631, p = 0.028), and positively correlated with the peripheral blood eosinophil count (r = -0.719, p = 0.008). Changes in √WA at Pi10 after one year were positively correlated with changes in the mucus score (r = 0.742, p = 0.007). This study has limitations, including its single-arm observational design and the small sample size. However, BT led to a symptomatic improvement in patients with severe asthma. The validated "√WA at Pi10" metric on CT effectively evaluated the therapeutic response in Japanese asthma patients after BT.

Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis.

Asthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma. Our aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under "real-world" conditions. This was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0. Twenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable. In this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function.

Real-world outcomes of mepolizumab for the treatment of severe eosinophilic asthma in Canada: an observational study

BackgroundMepolizumab, the first widely available anti-interleukin 5 biologic, targets eosinophilic inflammation and has been shown in clinical trials to reduce exacerbations, oral corticosteroid dependence, and healthcare utilization in patients with severe asthma. The impact of mepolizumab in a real-world, publicly funded healthcare setting is unknown. The objective of this study was to describe the demographics and clinical characteristics of real-world patients receiving mepolizumab, and to compare asthma-related outcomes and associated asthma-related costs before and during mepolizumab use.MethodsThis retrospective, observational study in Ontario, Canada, included patients initiating mepolizumab between February 2016 and March 2019. Patients were identified using the mepolizumab patient support program and linked to the Institute for Clinical Evaluative Sciences database of publicly accessed healthcare. Patient outcomes were obtained for 12 months pre- and post-mepolizumab initiation and compared.ResultsA total of 275 patients were enrolled in the overall patient support program cohort (mean [standard deviation] age 57.6 [13.5] years, mean [standard deviation] of the median per-patient eosinophil count 540.4 [491.9] cells/μL). Mepolizumab was associated with reductions in asthma exacerbations (46.1%, P < 0.001) and in the number of asthma-related visits to general practitioners (40.2%, P < 0.001), specialists (27.2%, P < 0.001), and emergency departments (52.1%, P < 0.001). Associated costs were significantly lower post- versus pre-mepolizumab for asthma-related general practitioner and specialist visits, and for all-cause emergency department visits and hospital admissions.ConclusionsIn a real-world population of Canadian patients with severe asthma with an eosinophilic phenotype, the use of mepolizumab within a patient support program reduced asthma exacerbations and decreased asthma-related healthcare resource utilization and associated costs.

Outcomes of Serum Food-Specific Immunoglobulin G 4 to Guide Elimination Diet in Patients With Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes. Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up. Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up. Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.

Blood Eosinophil Count and Its Determinants in a Chinese Population-Based Cohort

Introduction: Blood eosinophil count has been shown markedly variable across different populations. However, its distribution in Chinese general population remains unclear. We aimed to investigate blood eosinophil count and its determinants in a Chinese general population. Methods: In this population-based study, general citizens of Sichuan province in China were extracted from the China Pulmonary Health study. Data on demographics, personal and family history, living condition, lifestyle, spirometry, and complete blood count test were obtained and analyzed. A stepwise multivariate binary logistic regression analysis was performed to identify determinants of high blood eosinophils (>75th percentile). Results: A total of 3,310 participants were included, with a mean age (standard deviation) of 47.0 (15.6) years. In total population, the median blood eosinophil count was 110.0 (interquartile range [IQR]: 67.2–192.9) cells/μL, lower than that in smokers (133.4 cells/μL, IQR: 79.3–228.4) and patients with asthma (140.7 cells/μL, IQR: 79.6–218.2) or post-bronchodilator airflow limitation (141.5 cells/μL, IQR: 82.6–230.1), with a right-skewed distribution. Multivariate analyses revealed that oldness (aged ≥60 years) (odds ratio [OR]: 1.66, 95% confidence interval [CI]: 1.11–2.48), smoking ≥20 pack-years (OR: 1.90, 95% CI: 1.20–3.00), raising a dog/cat (OR: 1.72, 95% CI: 1.17–2.52), and occupational exposure to dust, allergen, and harmful gas (OR: 1.58, 95% CI: 1.15–2.15) were significantly associated with high blood eosinophils. Conclusion: This study identifies a median blood eosinophil count of 110.0 cells/μL and determinants of high blood eosinophils in a Chinese general population, including oldness (aged ≥60 years), smoking ≥20 pack-years, raising a dog/cat, and occupational exposure to dust, allergen, and harmful gas.

Clinical implications of peripheral eosinophil count at diagnosis in patients newly diagnosed with microscopic polyangiitis and granulomatosis with polyangiitis

BackgroundThis study investigated the clinical implications of peripheral eosinophil count at diagnosis in estimating cross-sectional antineutrophil cytoplasmic antibody-associated vasculitis (AAV) activity and predicting all-cause mortality during follow-up in patients newly diagnosed with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).MethodsThis study included 224 immunosuppressive drug-naïve patients with peripheral eosinophil count at diagnosis < 1,000/mm3. The Birmingham Vasculitis Activity Score (BVAS), the Five-Factor Score (FFS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at diagnosis were assessed.ResultsThe median age of the 224 patients (152 MPA and 72 GPA) was 62.0 years; 35.3% of them were men. At diagnosis, peripheral eosinophil count was significantly correlated with BVAS (P = 0.001), FFS (P = 0.046), ESR (P < 0.001), and CRP (P < 0.001). Deceased patients had a significantly higher median peripheral eosinophil count at diagnosis than surviving patients (310.0/mm3 vs. 170.0/mm3, P = 0.004). In addition, patients with MPA and those with cardiovascular and renal manifestations at diagnosis exhibited significantly higher peripheral eosinophil counts than those without. When the optimal cut-off of peripheral eosinophil count at diagnosis for all-cause mortality during follow-up was set at 175.0/mm3, Patients with peripheral eosinophil count at diagnosis ≥ 175.0/mm3 exhibited a significantly lower cumulative patients’ survival rate than those with peripheral eosinophil count at diagnosis < 175.0/mm3 (P = 0.008).ConclusionsThis study was the first to demonstrate that peripheral eosinophil count at diagnosis could estimate cross-sectional AAV activity at diagnosis and contribute to predicting all-cause mortality during follow-up in MPA and GPA patients.

Early Elevation of Absolute Eosinophil Count after Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Chronic Graft-Versus-Host Disease in Children

BACKGROUND Chronic graft-versus-host disease (cGVHD) is the most frequent late complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with non-relapse mortality. If recipients with cGVHD are not properly treated at the appropriate time, cGVHD can lead to severe complications. Therefore, early prediction of cGVHD is required to improve quality of life among the pediatric survivors who undergo allo-HSCT. The significance of eosinophilia in peripheral blood after allo-HSCT remains to be elucidated. Previous studies found that eosinophilia after allo-HSCT reduced the risk of relapse of malignancies or non-relapse mortality and was also associated with cGVHD. However, the subjects of these reports were mainly adults and there were limited data focused on eosinophilia after allo-HSCT in children. The aim of this study was to evaluate whether an early elevation of absolute eosinophil count after allo-HSCT was associated with the development of cGVHD in children. METHODS A total of 165 consecutive patients who received allo-HSCT in our institute were included. Patients who had previously received allo-HSCT, relapsed or died before day 100, and did not achieve engraftment, were excluded. Eosinophilia was defined as an eosinophil count of more than 500 /µL in peripheral blood within 60 days of stem cell infusion. The primary outcome of the present study was the development of cGVHD. RESULTS In our cohort, eosinophilia was detected in 67 patients (40.6%), with a median maximum eosinophil count of 1,050 /µL (range, 504 - 7,812 /µL) at a median of 40 days (range, 24 - 59 days), while median maximum eosinophil count in those without eosinophilia was 189 /µL (range, 0 - 495 /µL). There were no significant differences between the patients with or without eosinophilia in disease type, graft source, donor type, conditioning regimen, and GVHD prophylaxis and treatment. The median time from day 0 to the date of diagnosis of cGVHD was 120 days (range, 100 - 1,302 days). The cumulative incidence rate of cGVHD at 3 years in the entire cohort was 39.3% (95% confidence interval: 32.2 - 47.4). Patients with eosinophilia had a higher 3-year cumulative incidence rate of cGVHD, compared with those without eosinophilia (49.1% vs. 32.7%, P = 0.007). Cox proportional hazards model analysis with adjustments for the potential confounding factors of HLA mismatched donor, unrelated donor, aGVHD, use of ATG as conditioning regimen revealed that eosinophilia was associated with an increased risk of cGVHD (adjusted hazard ratio: 2.12; 95% confidence interval: 1.16-3.85, P = 0.014). In the 165 patients who underwent allo-HSCT, there was no significant difference in 5-year overall survival (OS) between the eosinophilia and the non-eosinophilia groups (80.1% vs. 80.5%, P=0.76). In the 121 patients with malignant diseases, there was no significant difference in 5-year OS between the eosinophilia and the non-eosinophilia groups (75.5% vs. 76.3%, P = 0.70). There was also no significant difference in 5-year disease-free survival between the eosinophilia and the non-eosinophilia groups (69.1% vs. 77.1%, P = 0.34). On the other hand, there was a significant difference in 5-year GVHD-free relapse-free survival between the eosinophilia and the non-eosinophilia groups (41.1% vs. 62.4%, P = 0.04). DISCUSSION &amp; CONCLUSION In the present study, we revealed that an early elevation of absolute eosinophil count after allo-HSCT was associated with cGVHD in children. Because eosinophilia after allo-HSCT occurs before the development of cGVHD, early eosinophilia after allo-HSCT may predict the development of cGVHD in children.

Dupilumab for relapsing or refractory sinonasal and/or asthma manifestations in eosinophilic granulomatosis with polyangiitis: a European retrospective study

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We...

Association of blood total immunoglobulin E and eosinophils with radiological features of bronchiectasis

BackgroundOur study aimed to investigate whether serum total IgE and blood eosinophils were associated with radiological features of bronchiectasis in a Chinese cohort.MethodsWe retrospectively enrolled bronchiectasis patients who visited Peking University Third Hospital from Jan 1st, 2012 to Oct 7th, 2021. The clinical, laboratory and chest CT characteristics were analyzed in association with serum total IgE level and blood eosinophil count.ResultsA total of 125 bronchiectasis patients were enrolled, with 50.4% (63/125) female, and a mean age of 62.4 ± 14.1 years. The median serum total IgE level and blood eosinophil count were 47.7 (19.8, 123.0) KU/L and 140 (90, 230) cells/µl, respectively. In patients with a higher than normal (normal range, 0–60 KU/L) total IgE (43.2%, n = 54), more lobes were involved [4 (3, 5) vs. 3 (2, 4), p = 0.008], and mucus plugs were more common (25.9% vs. 9.9%, p =0.017) on HRCT, as compared to those with a normal level of total IgE. The higher IgE group was more likely to have bilateral involvement (p = 0.059), and had numerically higher Smith and Bhalla scores, but the differences were not statistically significant. In patients with an eosinophil count ≥ 150 cells/µl (49.6%, n = 62), the number of lobes involved was greater [4 (3, 5) vs. 3 (2, 4), p = 0.015], and the Smith and Bhalla scores were higher [9 (5, 12) vs. 6 (3, 9), p = 0.009, 7 (5, 11) vs. 5 (3, 9), p = 0.036]. The Smith score was correlated positively with the eosinophil count (r = 0.207, p = 0.020). Fractional exhaled nitric oxide (FeNO) was correlated with total IgE (r = 0.404, p = 0.001) and eosinophil count (r = 0.310, p = 0.014).ConclusionsOur study demonstrated that serum total IgE and the blood eosinophil count were associated with the radiological extent and severity of bronchiectasis, necessitating further investigation on the role of T2 inflammation in structural abnormalities of this heterogeneous disease.

Effect of abrocitinib and dupilumab on eosinophil levels in patients with moderate‐to‐severe atopic dermatitis

AbstractBackgroundEosinophilia is common in patients with atopic dermatitis (AD). Abrocitinib, an oral Janus kinase‐1 inhibitor and dupilumab, an anti–interleukin‐4 receptor‐α antibody, are approved for moderate‐to‐severe AD. Dupilumab has been associated with transient eosinophilia.ObjectivesTo assess the effect of abrocitinib and dupilumab on eosinophils in patients from the phase 3 JADE COMPARE (NCT03720470) and JADE EXTEND (NCT03422822) trials.MethodsIn JADE COMPARE, patients received once‐daily oral abrocitinib (200/100 mg), placebo or subcutaneous dupilumab (300 mg, biweekly) with background topical therapy. In the ongoing long‐term JADE EXTEND study (Data cutoff: April 22, 2020), dupilumab‐treated patients from JADE COMPARE received once‐daily abrocitinib (200/100 mg) with background topical therapy. The proportion of patients with eosinophilia and hypereosinophilia, and association of eosinophilia with clinical efficacy was assessed. Adverse events (AEs) were also assessed.ResultsOf the 837 patients in JADE COMPARE, 58 (25.7%), 47 (19.7%) and 51 (21.1%) had eosinophilia at baseline in the abrocitinib 200 mg, abrocitinib 100 mg and dupilumab groups, respectively. At Week 16, eosinophilia decreased with abrocitinib 200 mg (9.3%) and abrocitinib 100 mg (19.0%) but not dupilumab (21.5%); no cases of hypereosinophilia were observed with abrocitinib 200 mg compared with abrocitinib 100 mg (1.9%) and dupilumab (2.3%). Decreases in median eosinophil counts were greater with abrocitinib 200 mg (difference, −100/mm3) and abrocitinib 100 mg (−70/mm3) than dupilumab (+25/mm3) or placebo (+30/mm3) at Week 16. Similar trends were observed in patients with comorbid asthma and allergic rhinitis. Eosinophilia decreased from baseline to Week 12 in dupilumab‐treated patients who switched to abrocitinib in JADE EXTEND. Decreased eosinophil counts with abrocitinib correlated positively with improvements in AD severity, itch and sleep loss. No eosinophilia‐associated AEs occurred.ConclusionsAbrocitinib decreased eosinophilia in patients with moderate‐to‐severe AD who had baseline eosinophilia. Resolution of eosinophilia was associated with abrocitinib clinical efficacy.

Eosinophilia in patients with melanoma under treatment with immune checkpoint inhibitor-based regimens.

e21528 Background: Immune-related eosinophilia (irEo) has been described as an adverse event of immune checkpoint inhibitors (ICI), but its rate, severity, duration, clinical significance, diagnostic approach, and management have not been analysed. In the present study we analyse these features in patients with melanoma. Methods: We reviewed the files of patients with advanced/metastatic melanoma treated with ICI-based regimens in a tertiary university referral centre, to describe the rate of eosinophilia, along with the baseline disease characteristics, severity, type of treatment, time on treatment, maximum eosinophil count, and symptoms, as well as its diagnostic evaluation and management, course, and prognostic implications. Results: A total of 249 patients were included in the analysis. Eosinophilia was present in 61 (24.5%) and there was no correlation with gender, age, histologic type, stage, or BRAF mutation status. The median time interval from treatment initiation to the onset of eosinophilia was 55 days (10-534), while the median eosinophil count at first presentation was 0.70x109/L (0.50-4.53x109/L), and the maximum eosinophil count was 1.07x109/L (0.50-13.22 x109/L). The rate of eosinophilia was significantly higher in patients treated with nivolumab plus bempegaldesleukin (50.0%), followed by nivolumab plus ipilimumab (21.7%). Symptomatic patients [N = 15, mostly pruritus, rash, arthralgia] and/or patients with hypereosinophilia (eosinophil count &gt; 1.5x109/L, N = 3 at first presentation, N = 20 during the course of eosinophilia) were assessed for organ involvement and for the cause of eosinophilia (CBC with blood smear, biochemistry profile including LDH, and uric acid, cardiac troponin, chest X-ray, and heart ultrasound). Further evaluation was performed according to the clinical scenario and the findings of the initial evaluation. In none of the patients a definitive diagnosis of eosinophilia was reached; thus, all cases were deemed irEo. None of the patients was acutely ill. Patients without findings or hypereosinophilia did not require medical intervention, while the remaining were managed with low-to-medium doses of corticosteroids (N = 2), antihistamines (N = 11), or local treatment (N = 4). Two patients had to delay treatment, and one (max count 13.2x109/L) had to permanently discontinue bempegaldesleukin and continue on nivolumab monotherapy. Eosinophilia relapsed in 21 patients when rechallenged with the same or different immunotherapy regimen. There was a non-significant trend for longer overall survival in patients with eosinophilia (64.5 months vs 33.4 months, p = 0.16). Conclusions: This is the first study evaluating the association between the type of immunotherapy and the rate of eosinophilia in patients with melanoma and analysing the baseline characteristics of the patients as well as their diagnostic evaluation and management, course, and prognosis.

Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study

BackgroundThe efficacy of benralizumab has been broadly demonstrated in severe eosinophilic asthma (SEA), but only few real-life studies evaluated its long-term effects. Here we present novel data from the ANANKE study in which a large cohort of SEA patients was treated for up to 96 weeks.MethodsANANKE (NCT04272463) is an observational retrospective Italian study investigating the key characteristics of SEA patients (collected during the 12 months prior to benralizumab initiation) and the clinical outcomes during benralizumab treatment (annual exacerbation rate [AER], lung function, asthma control, OCS use, healthcare resource utilization). A post hoc analysis was also conducted in groups of patients based on history of previous biologic therapy (bio-experienced versus naïve patients). Analyses were descriptive only.ResultsBefore benralizumab initiation, evaluable SEA patients (N = 162, 61.1% females, mean age 56.0 ± 12.7) showed a median blood eosinophil count (BEC) of 600 cells/mm3 (IQR: 430–890). Patients experienced frequent exacerbations (annualized exacerbation rate [AER]: 4.10, severe AER: 0.98), with impaired lung function and poor asthma control (median ACT score: 14) despite 25.3% reported oral corticosteroid (OCS) use. Nasal polyposis was present in 53.1% patients; 47.5% patients were atopic. After 96 weeks since the start of benralizumab, nearly 90% patients were still on treatment; benralizumab dramatically decreased exacerbations (AER: − 94.9%; severe AER: − 96.9%), improved respiratory parameters (median increase in pre-bronchodilator forced expiratory volume [pre-BD FEV1]: + 400 mL) and asthma control (median ACT score: 23) while eliminating OCS in 60% patients. Importantly, benralizumab effects were either maintained or progressively improved over time, accompanied by a nearly complete depletion of BEC. Benralizumab reduced AER both in naïve (any AER: − 95.9%; severe AER: − 97.5%) and bio-experienced patients (any AER: − 92.4%; severe AER: − 94.0%).ConclusionsProfound and sustained improvements in all asthma outcomes were observed with benralizumab. The correct identification of patients’ eosinophilic-driven asthma phenotype was essential to ensure the achievement of such remarkable results.Trial registration: ClinicalTrials.gov Identifier: NCT04272463.

Use of methacoline challenge test to detect bronchial hyperresponsiveness in children with persistent rhinitis

Purpose: The incidence of persistent rhinitis in childhood is increasing day by day. Since bronchial hyperreactivity (BHR) and asthma can also be seen in a significant proportion of patients with persistent rhinitis, the use of markers that may indicate the risk of developing asthma in these patients is very important in clinical follow-up. In this study, it was aimed to demonstrate the relationship between persistent rhinitis and asthma in childhood using the bronchial methacoline challenge test (BMCT) and to investigate other factors associated with the risk of developing asthma in patients with persistent rhinitis.&#x0D; Materials and Methods: Patients aged 6-18 years who presented with findings of persistent rhinitis were evaluated with a detailed history, physical examination, and spirometry. Patients with normal examination findings and spirometry findings, and patients whose examination findings and nasal inflammation findings were compatible with moderate-to-severe rhinitis were included in the study, and their atopy status was evaluated by skin prick test, and their BHR was evaluated by BMCT.&#x0D; Results: Seventy-three patients were included in the study. The mean age was 9±2.7years, 45.2% of the patients were male. 63% of the patients were allergic and family history of allergy was present in 45.2% of the patients. 82.2% of the patients had BHR detected with BMCT. The median blood eosinophil count (BEC) was 320/mm3 and the IgE level was 160kU/L. Patients with atopy had statistically significantly higher IgE and BEC values compared with non-allergic patients. Patients with BHR were found to be younger, and had higher median BEC values. In multivariant analysis, it was observed that the patient's age300/mm3, and IgE levels&gt;250IU/L increased the probability of detecting BHR with BMCT. &#x0D; Conclusion: Care should be taken for every patient with persistent rhinitis because of the risk of BHR and asthma. Atopy examinations should be performed, but the possibility of developing BHR and asthma should not be overlooked even in the patients who are non- allergic.

Experimental infection with African Horse Sickness Virus in horses induces only mild temporal hematologic changes and acute phase reactant response.

African Horse Sickness (AHS) is a vector-borne disease endemic to sub-Saharan Africa caused by African Horse Sickness Virus (AHVS). Infections in naïve horses have high morbidity and mortality rates. AHS pathogenesis is not well understood; neither the hematologic changes nor acute phase response occurring during infection has been fully evaluated. The study's objective was to characterize the hematologic changes and acute phase response during experimental infection with AHSV. 4 horses negative for AHSV group-specific antibodies. In this prospective, longitudinal study conducted between November 23 and December 2, 2020, horses were experimentally infected with AHSV, and blood samples were obtained before inoculation and then every 12 hours until euthanasia. Hematologic changes and changes for serum amyloid A (SAA) and iron concentration were evaluated over time using a general linear model including natural logarithm of sampling time. All horses were humanely euthanized due to severe clinical signs typical of AHS. Median Hct increased significantly, and the median WBC count, monocyte count, eosinophil count, and myeloperoxidase index changed significantly in all horses over time. Horses developed marked thrombocytopenia (median, 48 X 103 cells/µL; range, 21 X 103 to 58 X 103 cells/µL) while markers of platelet activation also changed significantly. Median SAA increased and serum iron concentration decreased significantly over time. Results indicated severe thrombocytopenia with platelet activation occurs during infection with AHSV. Changes in acute phase reactants SAA and iron, while significant, were unexpectedly mild and might not be useful clinical markers.

Novel endoscopic approaches using the endocytoscopy for the target biopsy in esophageal eosinophilia.

Multiple biopsies are recommended for the diagnosis of eosinophilic esophagitis (EoE) because inflammatory changes are frequently patchy. Reports on EoE using endocytoscopy (ECS) are limited. This present study aimed to assess if diagnostic yield improves by adding ECS on conventional white light imaging (WLI) in patients with esophageal eosinophilia (EE). A total of 284 biopsy specimens from 71 patients with a known diagnosis of EE were enrolled and divided into the WLI group (156 specimens) or the ECS group (128 specimens). Four biopsies from 5 and 10cm proximal to the esophagogastric junction were taken from each patient. In the ECS group, the biopsy was performed where bilobed nuclei were observed. The biopsy sensitivity for EE, eosinophil count of a single specimen and the biopsy sensitivity of each endoscopic finding were evaluated between both groups. The sensitivity of a single biopsy specimen was higher in the ECS group than that of the WLI group (62.5 vs. 41.7%, P < 0.001). In addition, the median eosinophil count in the ECS group was significantly higher [19 vs. 6.5/high-power field (HPF), P < 0.001]. For each endoscopic finding, ECS-based biopsy had higher sensitivity than that of WLI in the diagnosis of edema (33.1 vs. 11.3%, P = 0.007) and linear furrows (75.8 vs. 52%, P = 0.005). This study showed that adding ECS to WLI improved the biopsy sensitivity and eosinophil detection in patients with EE.

Structured histopathology and laboratory evidence in nasal polyposis with different pathogenesis

PurposeNon-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD), intrinsic asthma, eosinophilic granulomatosis with polyangiitis (EGPA) and odontogenic sinusitis may be associated with nasal polyps. The aim of the study was to compare circulating inflammatory cells and structural histopathology of these groups of nasal polyposis. MethodsWe retrospectively evaluated 71 patients with nasal polyps stratified according to the above-mentioned pathogenesis. All patients underwent preoperative laboratory investigations and primary endoscopic sinus surgery. Surgical specimens were submitted to structured histopathological evaluation. ResultsThe median tissue eosinophil count (cells/HPF) was significantly different between the considered groups of nasal polyposis (p=0.0004). The median of NERD sub-cohort was significantly higher than intrinsic asthma (p=0.0030), odontogenic CRS (p=0.0001) and EGPA ones (p=0.0094). Eosinophilic aggregates positive rate was significantly higher in NERD sub-cohort than in odontogenic CRS (p=0.0072), EGPA (p=0.0497) and asthma (p=0.0188) ones. EGPA sub-cohort had a higher neutrophil infiltrate positive rate than NERD (p=0.0105) and intrinsic asthma ones (p=0.0040). Odontogenic CRS sub-cohort had a higher neutrophil infiltrate positive rate than NERD (p=0.0140) and asthma ones (p=0.0096). EGPA sub-cohort had a higher presence of fibrosis than NERD (p=0.0237) and odontogenic CRS sub-cohort (p=0.0107). Odontogenic sub-cohort had a lower sub-epithelial edema positive rate than NERD (p=0.0028) and asthma (p=0.0149) ones. ConclusionsStructural histopathology may identify nasal polyps histotypes with different morphological patterns. The identified histopathological features can facilitate the recognition of rational therapeutic and follow-up approaches that consider the tissue modifications associated with the response to drugs and surgery.

Hematological and Biochemical changes in Schistosoma mansoni infected patients at Haik Primary Hospital, North-East Ethiopia: A comparative cross-sectional study.

Schistosomes are blood dwelling parasites that affect more than 260 million people globally, and over 800 million people are at risk of infection in 74 countries. It causes acute and chronic debilitating diseases. The parasite is reported to alter the hematological and biochemical parameters in humans. Therefore, this study was aimed to evaluate the hematological and biochemical changes in S. mansoni infected adult patients compared to apparently healthy controls. A comparative cross-sectional study was conducted at Haik Primary Hospital from February to April 2021. One hundred and eighty study participants consisting of 90 S. mansoni infected patients and 90 apparently healthy controls were recruited using systematic random sampling method. Socio-demographic characteristics and other variables were collected using questionnaires. Stool sample was examined microscopically to detect S. mansoni infection using direct wet mount and Kato Katz technique. In apparently healthy controls, S. mansoni infection was rule out using direct wet mount and Kato Katz technique. Moreover, the intensity of S. mansoni infection was assessed using Kato Katz technique. Blood sample was collected from each study participant to determine the hematological and biochemical profiles. Data were entered in to Epi Data version 3.1 and analyzed using SPSS version 26.0 software. Kolmogorov-Smirnov and Shapiro Wilk normality tests were done to assess the distribution of continuous variables. The Mann-Whitney U test and Kruskal Wallis H test was done to compare the differences among nonnormally distributed variables between S. mansoni infected patients and healthy controls. P-values <0.05 at 95%CI were considered as statistically significant. The mean age (SD) of S. mansoni infected patients and apparently healthy controls was 30.33 (±12.26) and 31.2 (±12.85) years old, respectively. The prevalence of anemia, and thrombocytopenia among S. mansoni infected patients were 23.3% and 26.7%, respectively. Erythrocytic sedimentation rate (ESR) was significantly elevated among S. mansoni infected patients than apparently healthy controls. The median white blood cell count, red blood cell count, red blood cell indices, and platelet indices were significantly lower among S. mansoni infected patients compared to apparently healthy controls (P<0.05). On the other hand, the median eosinophil count was significantly elevated among S. mansoni infected patients compared to apparently healthy controls (P<0.05). This study also showed significantly elevated values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and direct bilirubin and lower albumin, total cholesterol and triglycerides among S. mansoni infected patients compared to apparently healthy controls. Kruskal Wallis H test showed a significant difference in the median of most hematological and biochemical parameters between moderate and heavy intensity of infection with light intensity of infection and apparently healthy controls. The findings of this study showed significantly altered hematological values and liver function tests among S. mansoni infected patients compared to apparently healthy controls. Therefore, screening of S. mansoni infected patients for various hematological and biochemical parameters and providing treatment to the underlying abnormalities is very crucial to avoid schistosomiasis associated morbidity and mortality.