Higher Eosinophil Research Articles

Stability of blood eosinophils in acute exacerbation of chronic obstructive pulmonary disease and its relationship to clinical outcomes: a prospective cohort study

BackgroundThe clinical value of blood eosinophils and their stability in chronic obstructive pulmonary disease (COPD) remains controversial. There are limited studies on association between the stability of blood eosinophils in acute exacerbation of COPD (AECOPD) and clinical outcomes. This study aimed to evaluate the stability of blood eosinophils in hospitalized AECOPD and its relationship to clinical outcomes.MethodsThis prospective observational study recruited patients hospitalized with AECOPD from November 2016 to July 2020. The eligible patients were divided into four groups according to their blood eosinophil counts at admission and discharge: persistently < 300 cells/μl (LL), < 300 cells/μl at admission but ≥ 300 cells/µl at discharge (LH), ≥ 300 cells/μl at admission but < 300 cells/µl at discharge (HL), and persistently ≥ 300 cells/μl (HH). Cox hazard analyses were used to study the association between eosinophil changes and exacerbations or mortality.ResultsIn 530 patients included, 90 (17.0%) had a high blood eosinophil count (BEC) ≥ 300 cells/µl at admission but 32 (35.6%) of them showed a decreased BEC at discharge. The proportions and distribution for group LL, LH, HL, and HH were 381 (71.9%), 59 (11.1%), 32 (6.0%), and 58 (10.9%), respectively. During hospitalization, the LH group had a higher C-reactive protein level, higher rate of intensive care unit (ICU) admission, and higher total cost. The length of hospital stay of the LH group was longer compared with group LL, HL, or HH (P = 0.002, 0.017, and 0.001, respectively). During a follow-up of 12 months, the HH group was associated with a higher risk of moderate-to-severe exacerbations compared to the LL group (hazard ratio 2.00, 95% confidence interval 1.30–3.08, P = 0.002). Eosinophil changes had no significant association with mortality at 12 months. Sensitivity analyses in patients without asthma and without use of systemic corticosteroids prior to admission did not alter the results.ConclusionsMore attention should be paid to the LH group when evaluating the short-term prognosis of AECOPD. A persistently high BEC was a risk factor for long-term exacerbations. Eosinophil changes during hospitalization could help to predict outcomes.

The characteristics and clinical significance of elevated serum IgG4/IgG levels in patients with Graves' disease.

This study aims to further explore the clinical and laboratory characteristics of patients with GD with high serum IgG4 based on the IgG4/IgG ratio. This study is a prospective observational study. A total of 25 normal controls and 84 people newly diagnosed with GD were enrolled in this study. Taking the IgG4/IgG ratio of 8% as the cutoff value, the experimental groups were further divided into two subgroups: the high IgG4/IgG subgroup and the normal IgG4/IgG subgroup. We evaluated the differences in clinical characteristics and laboratory parameters between the groups. The IgG4, IgG4/IgG, and IL-17 of the newly diagnosed GD group were significantly higher than those of the normal control group (P < 0.05). The differences in age, IL-1β, IL-17, and eosinophil count between the high IgG4/IgG subgroup and the normal IgG4/IgG subgroup were statistically significant (P < 0.05). After ATD treatment, some patients developed allergies; the high IgG4/IgG subgroup was significantly higher than the normal IgG4/IgG subgroup (χ2 = 4.424, P = 0.035). After 3 months of ATD treatment in patients with GD, the TRAb in the normal IgG4/IgG subgroup were significantly lower than before (P < 0.05), while the difference in the high IgG4/IgG subgroup was not statistically significant (P > 0.05). A small portion of patients with GD harbored elevated serum IgG4/IgG levels. They are younger, have higher eosinophils, and are more prone to allergies; also, they have higher levels of cytokines IL-1β and IL-17 and their remission is not easily attained after treatment with ATD; this could be due to the instability of the Th17/Treg cell balance.

Blood Eosinophils and Pulmonary Rehabilitation in COPD.

Background Blood eosinophils predict the response to therapy, risk of exacerbation, and readmission in COPD. This study investigates whether blood eosinophils predict pulmonary rehabilitation (PR) outcomes in COPD. Methods We categorized patients into eosinophilic (blood eosinophils ≥300 cells/ml) or noneosinophilic (<300 cells/ml). In a retrospective design, we compared changes within and between the two groups on BODE index, 6-minute walk test (6MWT), FEV1, and mMRC dyspnea scale. Results Of 206 patients enrolled, 176 were included for analysis; 90 were eosinophilic. BODE index improved in both groups: (MD −1.25; 95% CI (−0.45, −4.25), P ≤ 0.001) in the eosinophilic and (MD −1.33; 95% CI (−1.72, −0.94), P ≤ 0.001) in the noneosinophilic, but a higher BODE index remained in the eosinophilic (4.98); adjusted mean change (β): 0.7 (95% CI (0.15, 1.26), P=0.01). 6MWT improved by 29.3 m in the eosinophilic (95% CI (14.2, 44.4), P ≤ 0.001) vs. 115.1 m in the noneosinophilic (95% CI (−30.4, 260.6), P=0.12). FEV1 did not change in the eosinophilic (MD −0.6; 95% CI (−2.64, 1.48), P=0.58), but improved by 2.5% in the noneosinophilic (MD 2.5; 95% CI (0.77, 4.17), P=0.005). There were no significant between-group differences in 6MWT and FEV1; adjusted mean changes (β) were −9.69 m (95% CI (−39.51, 20.14), P=0.52) and −2.31% (95% CI (−5.69, 1.08), P=0.18), respectively. There were no significant within- or between-group changes in the mMRC scale. Conclusion Although PR improves the BODE index in both eosinophilic and noneosinophilic COPD, a higher eosinophil count (≥300 cells/ml) is associated with a higher (worse) BODE index. Blood eosinophils may predict PR outcomes.

Real-Life Effectiveness of Mepolizumab on Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity in Patients with Severe Eosinophilic Asthma.

Severe eosinophilic asthma (SEA) is associated with high peripheral blood and airway eosinophilia, recurrent disease exacerbations and severe airflow limitation. Eosinophilic inflammation is also responsible for small airway disease (SAD) development. SEA patients experience poor disease control and response to standard therapy and are prime candidates for anti-IL5 biologicals, such as mepolizumab, but the effect of treatment on SAD is unclear. We investigated the effect of mepolizumab on lung function in SEA patients, focusing on SAD parameters, and searched for an association between patients’ phenotypic characteristics and changes in small airways function. In this real-life study, data from 105 patients with SEA were collected at baseline and after 6, 12 and 18 months of mepolizumab treatment. Along with expected improvements in clinical and lung function parameters brought by Mepolizumab treatment, FEF2525-75% values showed a highly significant, gradual and persistent increase (from 32.7 ± 18.2% at baseline to 48.6 ± 18.4% after 18 months) and correlated with ACT scores at 18 months (r = 0.566; p ≤ 0.0001). A patient subgroup analysis showed that changes in FEF25-75% values were higher in patients with a baseline peripheral blood eosinophil count ≥400 cells/μL and oral corticosteroid use. Mepolizumab significantly improves small airway function. This effect correlates with clinical benefits and may represent an accessible parameter through which to evaluate therapeutic response. This study provides novel insights into the phenotypic characteristics associated with the improved functional outcome provided by mepolizumab treatment.

Long-term predictors of severe exacerbations and mortality in a cohort of well-characterised adults with asthma

BackgroundWe aimed to explore long-term predictors of severe exacerbations and mortality in adults with well-characterised asthma.Study design and methodsAdults (aged ≥ 15) with an objectively verified diagnosis of asthma were recruited from a Danish respiratory outpatient clinic between 1974 and 1990. All individuals were followed in Danish registries for vital status, hospital admissions for asthma and cause of death until end of 2017. Predictors of exacerbations were obtained from a repeated measures model. Standardised mortality rates (SMR) for all-causes were compared with the Danish background population. Hazard ratios for mortality were obtained from a cox proportional hazards model in a two-step process.ResultsAt baseline, the cohort comprised 1071 patients (mean age 38, SD 16, 61% women), of whom 357 (33%) died during follow-up, with 93 (26%) dying from asthma (primary diagnosis). We found an SMR of 1.24 (95% CI 1.11–1.37, p < 0.001) for all-cause mortality. Baseline predictors for asthma-related death and repeated severe exacerbations were increasing age, ever smoker, FEV1 < 80% pred., high blood eosinophils, longer duration of symptoms and use of SABA > twice daily. Being non-atopic, having a positive histamine challenge test and symptoms more than twice a week were also predictors of repeated exacerbations.ConclusionsMarkers of poor asthma control, including high use of SABA, are predictors of long-term exacerbation rate and mortality over 30 years in patients with well-characterised asthma. Improving asthma control, including lung function and reducing use of reliever medication, is vital for improving the long-term outcome of asthma.

OCCULT COCCIDIOIDOMYCOSIS: A CASE OF PLEURAL COCCIDIOIDOMYCOSIS

TOPIC: Disorders of the Pleura TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coccidioides is a dimorphic fungus found in desert soil, native to parts of southwestern USA. Infection is acquired by inhalation of arthroconidia causing primary pulmonary coccidioidomycosis (Cocci) but patients can also present with unusual manifestations, which makes identifying Coccidioides infection challenging. We present a case of pleural cocci causing isolated right sided pleural effusion. CASE PRESENTATION: A Caucasian male aged 64, residing in Arizona for 40 years, presented with a 2-week history of dyspnea associated with right-sided pleuritic chest pain, anorexia, and 12-lbs weight loss in the past month. Vital signs were stable. Physical exam was significant for dullness to percussion and absent breath sounds on the right lung base. Initial labs were remarkable for a normal leukocyte count with eosinophilia at 6.6%. A chest x-ray showed a large, unilateral right pleural effusion with pleural thickening. CT imaging demonstrated a right-sided pleural effusion and nonspecific, left-sided pulmonary nodules. Thoracentesis was performed, removing 1800 ccs of serous fluid. Fluid studies were consistent with an exudative effusion. Nucleated cell count was 1230cells/mm3 with 40% eosinophils. Gram stain and culture for bacterial, fungal and acid-fast organisms were negative. Cytology was negative for malignant cells. Thoracoscopy showed inflammatory changes along with white studding on the pleural surface. Histopathology demonstrated pleura with granulomatous changes and was negative for organisms or malignancy. Screening antibodies for cocci came back positive and immunodiffusion complement-fixing showed a normal IgG but an elevated IgM level. A diagnosis of pleural cocci was made and fluconazole 400 mg daily was initiated. On a follow up visit after 6 weeks, complete resolution of the effusion and significant symptomatic improvement in the patient were noted. DISCUSSION: Symptomatic coccidioidomycosis commonly presents as community acquired pneumonia. Pleural effusions can be associated in 10% of patients with pulmonary cocci; however, it is unusual for an isolated pleural effusion to present without evidence of ipsilateral parenchymal infection, as was found in this patient. Malignancy should be ruled out in effusions with a high eosinophil count as in our patient and necessitated thoracoscopy. Pleural cocci can be diagnosed with a combination of pleural fluid analysis, blood serology, and thoracoscopy with pleural biopsy. There are no specific recommendations for treatment and our patient was treated with Azole dosed for pulmonary cocci. CONCLUSIONS: This case demonstrates that, rarely, Coccidioidomycosis can present as an isolated pleural effusion, without evidence of parenchymal involvement and requires a high index of suspicion with invasive testing to secure a diagnosis and initiate appropriate treatment. REFERENCE #1: Valdivia L, Nix D, Wright M, et al. Coccidioidomycosis as a common cause of community-acquired pneumonia [published correction appears in Emerg Infect Dis. 2006 Aug;12(8):1307]. Emerg Infect Dis. 2006;12(6):958-962. doi:10.3201/eid1206.060028 REFERENCE #2: John N. Galgiani, Neil M. Ampel, Janis E. Blair, Antonino Catanzaro, Francesca Geertsma, Susan E. Hoover, Royce H. Johnson, Shimon Kusne, Jeffrey Lisse, Joel D. MacDonald, Shari L. Meyerson, Patricia B. Raksin, John Siever, David A. Stevens, Rebecca Sunenshine, Nicholas Theodore, 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis, Clinical Infectious Diseases, Volume 63, Issue 6, 15 September 2016, Pages e112–e146, https://doi.org/10.1093/cid/ciw360 DISCLOSURES: No relevant relationships by Muhammad Arif, source=Web Response No relevant relationships by Arnold Forlemu, source=Web Response No relevant relationships by Abid Khokar, source=Web Response No relevant relationships by Ali Saeed, source=Web Response No relevant relationships by Hursh Sarma, source=Web Response No relevant relationships by Ayushi Sharma, source=Web Response

OVERLAP OF ASTHMA WITH ABPA AND EGPA BY DISEASE SEVERITY, EOSINOPHIL LEVELS, HEALTH CARE RESOURCE UTILIZATION, AND COSTS

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: Eosinophilic immune dysfunction (EID) is the dysregulation of mechanisms of eosinophil recruitment and activation, which may be a key mediator of many eosinophilic-driven diseases (EDDs). The overlap of asthma and other respiratory EDDs is not well understood.We aimed to quantify the overlap of asthma and allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatosis with polyangiitis (EGPA) according to asthma severity. We also examined eosinophil levels, health care resource utilization (HCRU), and total costs in patients with and without disease overlap. METHODS: REal-world inVestigation of Eosinophilic-Associated disease overLap (REVEAL) is a retrospective study using Optum Clinformatics claims data. Diagnoses and disease severity were determined from International Classification of Diseases (ICD) codes. REVEAL included data from patients with ≥2 years of continuous health plan enrollment and at least one diagnostic code for selected respiratory and eosinophilic diseases of interest. This analysis included 406,573 patients with asthma, 702 with EGPA, and 881 with ABPA during the period from January 1, 2015 to June 30, 2019. Descriptive statistics were used to analyze disease overlap. RESULTS: Of 406,573 patients with asthma, 588 (0.14%) had comorbid ABPA and 310 (0.08%) had comorbid EGPA. Disease overlap rates were greater for severe asthma than for mild to moderate asthma. (Severe asthma was defined as patients with a prescription for oral corticosteroids, an emergency room [ER] visit or inpatient hospitalization with a primary diagnosis code for asthma, or use of biologic therapy for asthma.) Of patients with mild to moderate asthma, 430 (0.13%) had ABPA and 192 (0.06%) had EGPA; of patients with severe asthma, 158 (0.23%) had ABPA and 118 (0.17%) had EGPA. High eosinophil levels (≥500 cells/µL) were more frequent in patients with asthma and ABPA (24.7%) or EGPA (24.8%) than in those with asthma alone (8.4%). All-cause HCRU per patient per month (including hospitalizations, inpatient length of stay [LOS], ER visits, and outpatient visits) and total all-cause costs (2020 US$) were higher in patients with asthma and ABPA or asthma and EGPA than in those with asthma alone (hospitalizations [mean]: 0.5 and 0.6 vs. 0.2; LOS [days]: 0.9 and 1.2 vs. 0.5; ER visits: 0.2 and 0.2 vs. 0.1; outpatient visits: 2.6 and 2.9 vs. 1.2; and costs: $8499.10 and $10,047.90 vs. $2628.80, respectively). CONCLUSIONS: We observed that asthma patients with comorbid ABPA or EGPA had more severe disease, greater levels of eosinophilia, and increased HCRU and costs, suggesting a central role of EID in disease severity. CLINICAL IMPLICATIONS: These findings have implications for quantifying unmet need, informing diagnostic and treatment approaches, and raising awareness about the role of EID in driving the development of multiple related conditions. DISCLOSURES: Employee relationship with AstraZeneca Please note: Aug 2020 to present Added 04/27/2021 by Anamaria Brailean, source=Web Response, value=Salary Employee relationship with AstraZeneca Please note: Aug 2020 to present Added 04/27/2021 by Anamaria Brailean, source=Web Response, value=Ownership interest Employee relationship with astrazeneca Please note: current Added 04/30/2021 by Rohit Katial, source=Web Response, value=Salary Employee relationship with AstraZeneca Please note: 2019 Added 05/10/2021 by Danuta Kielar, source=Web Response, value=Salary Employee relationship with Evidera Please note: Oct 2020 Onward Added 04/27/2021 by Yong Jin Kim, source=Web Response, value=Salary Consultant relationship with AstraZeneca Please note: October 2020 Onward Added 04/27/2021 by Yong Jin Kim, source=Web Response, value=Consulting fee Employee relationship with AstraZeneca Please note: 2014-current Added 04/27/2021 by Justin Kwiatek, source=Web Response, value=Salary No relevant relationships by Sharon MacLachlan, source=Web Response Employee relationship with AstraZeneca Please note: full time employee Added 04/28/2021 by Heide Stirnadel-Farrant, source=Web Response, value=Salary No relevant relationships by Michael Stokes, source=Web Response Employee relationship with AstraZeneca Please note: 2008 - now Added 04/27/2021 by Xiao Xu, source=Web Response, value=Salary

Comparing hospital admissions, comorbidities, and biomarkers between severe asthma and Gold III-IV chronic obstructive pulmonary disease.

In spite of difficulties in differentiating asthma from chronic obstructive pulmonary disease (COPD), physicians should strive for accurate diagnosis because outcomes may be different. Our aims were to compare the frequency of hospital admissions (HA) between severe asthmatic (SA) and Gold III-IV COPD subjects receiving disease-specific guideline recommended therapy and to depict the frequency of prevalent chronic disorders and the laboratorial profile suggesting allergic and eosinophilic phenotypes. This cross-sectional study comprises one group of SA subjects and another group of Gold III-IV COPD subjects. Subjects answered standard questionnaires, underwent spirometry, and provided a peripheral blood sample. We validated the HA that have occurred during the preceding year by review of the report emitted by the hospital. We detected comorbidities by review of current pharmacological therapies. We enrolled 160 SA and 41 Gold III-IV COPD subjects. As compared with Gold III-IV COPD subjects, SA subjects had lower odds of HA (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.05-0.74) and higher odds of obesity (OR 9.17, 95%CI 2.68-31.37), hypertension (OR 2.54, 95%CI 1.16-5.57), and diabetes mellitus (OR 5.71, 95%CI 1.56-20.85). The frequency of atopic and eosinophilic phenotypes was similar between study groups. Our results demonstrated that Gold III-IV COPD subjects had worse outcomes as compared with SA subjects. We also observed that the frequency of atopy and high peripheral blood eosinophil count were similar between study groups. Finally, we exposed aspects of comorbidities related to asthma and COPD that indicate the need of close monitoring the cardiovascular risk in SA subjects above 40 years of age.

Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels. The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy. Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300cells/μL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab-placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT). Adjusted mean difference (95% CI) (omalizumab-placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300cells/μL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity. Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence. ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 (https://clinicaltrials.gov/ct2/show/NCT03280550); POLYP 2: ClinicalTrials.gov identifier NCT03280537 (https://clinicaltrials.gov/ct2/show/NCT03280537).

Phenotypic Clustering in Non-Cystic Fibrosis Bronchiectasis Patients: The Role of Eosinophils in Disease Severity.

Whether high blood eosinophil counts may define a better phenotype in bronchiectasis patients, as shown in chronic obstructive pulmonary disease (COPD), remains to be investigated. Differential phenotypic characteristics according to eosinophil counts were assessed using a biostatistical approach in a large cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 906 patients who met the inclusion criteria were clustered into two groups on the basis of their eosinophil levels. The potential differences according to the bronchiectasis severity index (BSI) score between two groups (Mann–Whitney U test and eosinophil count threshold: 100 cells/µL) showed the most balanced cluster sizes: above-threshold and below-threshold groups. Patients above the threshold exhibited significantly better clinical outcomes, lung function, and nutritional status, while showing lower systemic inflammation levels. The proportion of patients with mild disease was higher in the above-threshold group, while the below-threshold patients were more severe. Two distinct clinical phenotypes of stable patients with non-cystic fibrosis (CF) bronchiectasis of a wide range of disease severity were established on the basis of blood eosinophil counts using a biostatistical approach. Patients classified within the above-threshold cluster were those exhibiting a mild disease, significantly better clinical outcomes, lung function, and nutritional status while showing lower systemic inflammatory levels. These results will contribute to better characterizing bronchiectasis patients into phenotypic profiles with their clinical implications.

Biologics modulate antinuclear antibodies, immunoglobulin E, and eosinophil counts in psoriasis patients.

Psoriasis is a chronic disease centered on tumor necrosis factor (TNF), interleukin (IL)-23, and IL-17 axis. While psoriasis patients benefit from biologics targeting TNF, IL-17s, and IL-23 nowadays, suppression of these molecules could modulate the balances of immune systems. However, the incidence of autoimmune disease and T-helper 2 reaction during biologic treatments for psoriasis patients is not well documented. We retrospectively examined antinuclear antibody (ANA), eosinophil counts, and immunoglobulin E (IgE) levels for psoriasis patients who underwent biologic treatments in our dermatology clinic from June 10, 2010 to January 29, 2020. A cumulative total of 199 biologic treatments were performed for a total of 128 psoriasis patients. Compared to the non-biologic group of 109 psoriasis patients who received non-biologic treatment, patients treated with infliximab showed more incidents of high ANA (14%, p=0.039) and high eosinophils (14%, p=0.021). The use of brodalumab increased incidents of high eosinophils (21%, p=0.005) but did not affect increase in ANA and IgE. The increase in high IgE level was observed significantly more during the use of risankizumab (15%, p=0.011). Methotrexate was the most frequently used concomitant systemic treatment, but methotrexate did not affect ANA, eosinophil counts, and IgE levels. Since the biologics for psoriasis treatment modulate the balance of T-helper cells, careful observation is required to detect unexpected changes of systemic immune conditions under biologic treatments.

Clinical Predictors of High Blood Eosinophils in Chronic Obstructive Pulmonary Disease.

PurposeElevated blood eosinophils have been implicated in chronic obstructive pulmonary disease (COPD) progression and exacerbation. We aim to investigate clinical predictors of high blood eosinophils in a Chinese COPD cohort.Patients and MethodsWe conducted a retrospective cohort study in Sichuan province, a Southwest province with high prevalence of COPD in China. All patients in this cohort were extracted from the Chinese Pulmonary Health study, a large cross-sectional study on COPD epidemiology in China. Demographics, personal and family history, living condition, spirometry and blood eosinophil counts were obtained. Univariate and multiple linear regression analyses were performed to determine predictors of high blood eosinophils.ResultsA total of 375 COPD patients were included in this cohort. The median absolute blood eosinophil count was 138.8 cells/μL, and the prevalence of COPD with high blood eosinophils was 66.7% and 14.7% when using the thresholds of 100 cells/μL and 300 cells/μL, respectively. Univariate analyses indicated that male gender, lower body mass index, high-density lipoprotein (HDL), lower family income, raising pets and biomass use were significantly associated with high blood eosinophils (p < 0.05). Multiple linear regression model further revealed male gender (unstandardized coefficient (B)=66.125, 95% confidence intervals (CI) 16.350 to 115.900, p=0.009), age (B=2.819, 95% CI 0.639 to 5.000, p=0.012) predicted high blood eosinophil level, whereas HDL (B=−64.682, 95% CI −123.451 to −5.914, p=0.031) was a negative predictor for high blood eosinophils.ConclusionThis retrospective cohort study suggests male gender, oldness and lower HDL could be clinical predictors of high blood eosinophils in Chinese COPD patients.

Clinical Outcome Prediction in COVID-19 Patients by Lymphocyte Subsets Analysis and Monocytes' iTNF-α Expression.

Simple SummarySeveral studies have explored the role of the inflammatory cells and cytokines involved in the protection or pathogenesis of coronavirus disease 2019. Unfortunately, the results have been controversial, and further studies are needed to better understand not only the roles but also the balance of these parameters, which are crucial data to improve prevention and treatment. As COVID-19 has a well-determined phasic progression and rapidly deteriorates approximately seven days after the onset of symptoms, it is extremely necessary to detect the clinical signs that are predictive of the outcome as early as possible. To this end, in this preliminary study, we evaluated the data relating to the monocyte intracellular TNF-α expression and lymphocyte subpopulations in peripheral blood collected from patients at admission and every day of hospitalization until day 7. Our findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcome of the coronavirus disease 2019.In December 2019, a novel coronavirus, “SARS-CoV-2”, was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

Eosinophilic granulomatosis with polyangiitis with an unusual presentation

Eosinophilic granulomatosis with polyangiitis is an ANCA vasculitis characterized by asthma, rhinosinusitis and peripheral eosinophilia. The kidney is infrequently involved, usually in the form of necrotizing crescentic glomerulonephritis. We present the case of a 60-year-old man who presented with painless sudden loss of visual acuity, purpuric exanthem in his legs, asthenia and myalgia. CT-scan ruled out acute vascular and intracranial space occupant lesions. Optical coherence tomography showed signs of left central retinal artery occlusion and perfusion deficits in the right arterial retinal blood supply. Complementary study showed prominent peripheral eosinophilia (24.500 cel/uL), increased serum IgE (1260U/L) and increased C-reactive protein (10.6mg/ dl). During admission, the patient presented with acute kidney failure (serum creatinine of 4.7mg/dl) and an exceptionally high p-ANCA MPO titer (&gt;600U/L). Eosinophilic granulomatosis with polyangiitis was diagnosed and plasmapheresis, pulse steroid therapy and intravenous cyclophosphamide were provided. Kidney biopsy showed interstitial nephritis with high eosinophil content while the glomerulus was relatively spared, with only mild endocapillary proliferation. The patient didn’t require dialysis. Kidney function was normal at discharge, although the visual deficit did not improve.

Efficacy and Safety of Prostaglandin D2 Receptor 2 Antagonism with Fevipiprant for Patients with Asthma: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

Accumulating evidence has shown that prostaglandin D2 (PGD2)-chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) pathway plays an important role in promoting eosinophilic airway inflammation in asthma. We aimed to assess the efficacy and safety of CRTH2 antagonist fevipiprant in patients with persistent asthma compared with placebo. We identified eligible studies by searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. The study was registered as CRD 42020221714 ( http://www.crd.york.ac.uk/PROSPERO ). Ten randomized controlled trials with 7902 patients met our inclusion criteria. A statistically significant benefit of fevipiprant compared with placebo was shown in improving forced expiratory volume in 1 s (MD 0.05 L, 95% CI: 0.02 to 0.07; p < 0.0001), Asthma Control Questionnaire score (MD -0.10, 95% CI: -0.16 to -0.04; p = 0.001), and Asthma Quality of Life Questionnaire score (MD 0.08, 95% CI: 0.03 to 0.13; p = 0.003). Fevipiprant decreased number of patients with at least one asthma exacerbation requiring administration of systemic corticosteroids for 3 days or more (RR 0.86, 95% CI: 0.77 to 0.97; p = 0.01). Some benefits were a little more pronounced in the high eosinophil population (with an elevated blood eosinophil count or sputum eosinophil percentage) and in the 450 mg dose group. Fevipiprant was well tolerated with no safety issues compared with placebo. Fevipiprant could safely improve asthma outcomes compared to placebo. However, most of the differences didn't reach the minimal clinically important difference (MCID), thus the clinical benefits remained to be confirmed.

Abstract 27: Early dynamics in peripheral blood immune cell subsets and ctDNA are predictive of outcome to immunotherapy

Abstract Background: Treatment-induced anti-tumor immune response may be reflected in peripheral blood leukocyte composition and shifts. The relative abundance of immune cell subsets captured by neutrophil-to-lymphocyte ratio (NLR) is a promising biomarker of response to immune checkpoint inhibition (ICI). However early dynamics and integration with circulating tumor DNA (ctDNA) kinetics during ICI have not been comprehensively studied. Methods: We evaluated the predictive role of early dynamic changes of peripheral immune cell subsets in 239 ICI treated metastatic non-small cell lung cancers (mNSCLC) and combined those with ctDNA dynamics in 18 early stage NSCLCs (esNSCLC) treated with neoadjuvant ICI. Blood cell counts were analyzed at baseline, 4 weeks on treatment, and at first radiographic follow up (mNSCLC) or preoperatively (esNSCLC). mNSCLC patients without progression at 6 months were considered to have durable clinical benefit (DCB). We employed eXtreme Gradient Boosting, a decision-tree based machine learning algorithm, to integrate baseline values and early changes in immune cell subsets. To reduce modeling overfitting, we trained an ensemble of models, incorporating 10-fold cross-validation that included feature selection (training n=171) and tested the model in an unseen independent set (n=68). For esNSCLCs, major pathologic response (MPR; ≤10% residual tumor; RT) was determined. We performed Targeted Error Correction next generation sequencing on 60 serial plasma and matched leukocyte DNA samples to assess ctDNA clonal dynamics. Changes in immune cell subsets were correlated with RT, MPR, progression-free (PFS) and overall survival (OS). Results: Our machine learning integrative model predicted DCB with an area under the ROC curve (AUC) of 0.96 for training, 0.72 for cross-validation testing and 0.74 for unseen testing datasets. Feature importance analysis revealed that NLR at 4 weeks, first radiographic follow up, and relative change in NLR from baseline were the strongest predictors of outcome together with relative eosinophil and lymphocyte count. Our model's performance was superior to TMB (AUC=0.52) or PD-L1 (AUC=0.54). For esNSCLCs, change in NLR at 4 weeks after ICI initiation was predictive of tumor regression (p=0.02), such that those with MPR showed significant decrease in NLR. This was also predictive of PFS (log rank p=0.004) and OS (log rank p=0.02). Furthermore, higher eosinophil count at 4 weeks was correlated with MPR (p=0.006) and decreased RT (p=0.006). Immune cell subset kinetics were concordant with ctDNA clearance in all but two patients and importantly NLR dynamics at 4 weeks were predictive of MPR even when ctDNA was undetectable. Conclusions: Early changes in peripheral immune cell subsets together with ctDNA are reflective of anti-tumor immune response during ICI and may more accurately predict ICI response than currently used biomarkers. Citation Format: Michael Hwang, Jenna Canzoniero, Samuel Rosner, Guangfan Zhang, Mara Lanis, Lamia Rhymee, Alexandria Curry, Gavin Pereira, Kristen Marrone, Joshua Reuss, Jarushka Naidoo, Christine Hann, Vincent Lam, Benjamin Levy, David Ettinger, Patrick Forde, Julie Brahmer, Victor Velculescu, Tanguy Seiwert, Valsamo Anagnostou. Early dynamics in peripheral blood immune cell subsets and ctDNA are predictive of outcome to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 27.

The Clinicopathologic Evaluation of Eosinophilic Cholecystitis: A Retrospective Observational Study in a Tertiary Care Center

Background: Eosinophilic cholecystitis (EC) is a rare form of cholecystitis that is diagnosed histopathologically. The aim of this study to evaluate the patient demographic features, laboratory findings and histopathologic characteristics of EC. The aim of this study to evaluate the patient demographic features, laboratory findings and histopathologic characteristics of EC.&#x0D; Design and setting: Retrospective observational study conducted in Erzurum, Turkey.&#x0D; Methods: Between June 2014 and June 2017 3,178 cholecystectomy specimens were reviewed retrospectively. Nineteen EC cases were included to the study. Parameters such as sex, age, clinical information, laboratory findings were obtained from information system of hospital. And the data of EC group were compared with a control group of 50 non-specific chronic cholecystitis patients (CC).&#x0D; Result: Out of 3,178 cholecystectomy specimens, 19 cases were diagnosed as EC (0.59%). Patients’ age ranged from 22-84 years and female to male ratio was 1.7:1. The average eosinophil count was 139.7 U/L in EC group. 11.7% of EC group had high level for eosinophils. In the EC group there were statistical significances between high eosinophil percentages and aspartate transaminase (AST), alkaline phosphatase (ALP) values (P&lt;0.05, P&lt;0.05). The EC group eosinophil levels were slightly higher than CC. Histopathologically, dense, severe infiltrates composed of eosinophils were seen.&#x0D; Conclusion: EC is a rare entity that can only diagnosed by histopathology. There were certain high levels in liver function tests and eosinophils in correlation with non-specific cholecystitis. Although the presentation may be similar to non-specific cholecystitis, if a postoperative histopathological diagnosis of EC is made, then the patient must be investigated thoroughly to rule out other associated disease conditions.

Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts

BackgroundIn the Phase III KRONOS study, triple therapy with budesonide/glycopyrronium/formoterol fumarate metered dose inhaler (BGF MDI) was shown to reduce exacerbations and improve lung function versus glycopyrronium/formoterol fumarate dihydrate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). However, whether the benefits related to the ICS component of BGF are driven by patients with high blood eosinophil counts (EOS) and/or airway reversibility has not been previously studied.MethodsKRONOS was a Phase III, double-blind, parallel-group, multicenter, randomized, controlled study of patients with moderate-to-very-severe COPD. Patients were randomized 2:2:1:1 to receive BGF 320/14.4/10 μg, GFF 14.4/10 μg, budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10 μg via a single Aerosphere inhaler, or open-label budesonide/formoterol fumarate dihydrate dry powder inhaler 400/12 μg (BUD/FORM DPI; Symbicort Turbuhaler) twice-daily for 24 weeks. Efficacy outcomes included in this post-hoc analysis were change from baseline in morning pre-dose trough FEV1 over weeks 12–24 and the rate of moderate-to-severe and severe COPD exacerbations. Adverse events in the non-reversible subgroup are also reported.ResultsOf 1896 patients analyzed, 948 (50%) were non-reversible and had EOS < 300 cells/mm3. In this group, BGF significantly improved morning pre-dose trough FEV1 versus BFF and BUD/FORM (least squares mean treatment difference, 95% confidence interval [CI] 69 mL [39, 99], unadjusted p < 0.0001 and 51 mL [20, 81], unadjusted p = 0.0011, respectively) and was comparable to GFF. BGF also significantly reduced annual moderate-to-severe exacerbation rates versus GFF (rate ratio [95% CI] 0.53 [0.37, 0.76], unadjusted p = 0.0005), with numerical reductions observed versus BFF and BUD/FORM. These results were similar for the overall study population. Safety findings were generally similar between non-reversible patients with EOS < 300 cells/mm3 and the overall population.ConclusionsIn patients with moderate-to-very-severe COPD without airway reversibility and EOS < 300 cells/mm3, BGF significantly improved morning pre-dose trough FEV1 versus BFF and BUD/FORM and significantly reduced the rate of moderate-to-severe exacerbations versus GFF. These findings demonstrate that BGF can provide benefits for a broad range of patients with COPD, and that the overall findings of the KRONOS primary analysis were not driven by patients with reversible airflow obstruction or high eosinophil counts.Trial registration ClinicalTrials.gov, NCT02497001. Registered 14 July 2015, https://clinicaltrials.gov/ct2/show/NCT02497001

Low Peripheral Blood Eosinophil Counts in Patients with Acute Graft-Versus-Host-Disease Prior to Systemic Corticosteroid Therapy Is Associated with Poor Prognosis

Background: Acute graft-versus-host-disease (aGVHD) is one of the main complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), occurring in about half of patients. Patients with grade II-IV aGVHD require treatment with systemic corticosteroids. However, 30% of them show steroid resistance, leading to poor prognosis. Thus, pretreatment prediction of steroid refractoriness allows for early secondary treatment introduction, which may improve aGVHD outcomes. The possible association between elevated peripheral blood (PB) eosinophil counts and the development of aGVHD has been previously reported. In contrast, several studies showed an association with better outcomes after allo-HSCT. These reports imply that PB eosinophil counts may predict prognosis in patients with aGVHD. In this study, we investigated the predictive role of pretreatment PB eosinophil counts in patients with aGVHD treated with systemic corticosteroid therapy.Methods: Retrospective case analysis was performed on 121 patients with hematological malignancies who underwent allo-HSCT between October 2010 and January 2017 in our institutes and developed any grade of aGVHD. We excluded patients who did not require systemic corticosteroid therapy (n=53), and who developed aGVHD after premature discontinuation of calcineurin inhibitors (n=5) because of relapse or calcineurin toxicities. Finally, a total of 63 patients were enrolled. PB smears obtained within 2 days before the start of systemic corticosteroid therapy were microscopically examined. The cut-off value of eosinophil counts for predicting survival was determined using receiver operating characteristic (ROC) curve analysis. The primary endpoint was 1-year overall survival (OS), measured from the start of systemic corticosteroid therapy to death due to any cause or the last follow-up. The secondary endpoints were 1-year progression-free survival (PFS), 1-year cumulative incidence (CI) of non-relapse mortality (NRM), and CI of relapse. OS and PFS were compared using the log-rank test and CIs of NRM and relapse were compared using Gray's test. Predictors of OS were evaluated using univariate and multivariate analysis using Cox's proportional hazards model.Results: The median age was 48 years (range: 40-59 years), and 31 patients (60.8%) were male. Primary diagnoses were acute myeloid leukemia (n=21), acute lymphoblastic leukemia (n=18), myelodysplastic syndrome (n=9), malignant lymphoma (n=13), multiple myeloma (n=1), and chronic myelomonocytic leukemia (n=1). They received bone marrow (n=38), peripheral blood stem cells (n=5), and cord blood (n=20). The median PB eosinophil count was 96/mm3 (range: 0-2903/mm3). ROC analysis revealed the cut-off value for predicting 1-year OS as 133/mm3 (area under the curve: 0.783; 95% confidence interval, 0.662-0.904). Thus, we defined patients with eosinophil counts ≥133/mm3 as the “high eosinophil group” (n=30) and the others as the “low eosinophil group” (n=33). There was no difference in clinical characteristics between the two groups, with the exception of days from transplantation to systemic corticosteroid therapy (29 days in the low eosinophil group vs. 43 days in the high eosinophil group, p<0.001). Regarding the primary endpoint, the 1-year OS rates were 65.2% and 93.3% in the low and high eosinophil groups, respectively (p=0.008) (Figure A). In the univariate analysis, the hazard ratio (HR) for 1-year OS of the low eosinophil group was 6.0 (95% confidence interval: 1.3-27.2, p=0.020). In the multivariate analysis adjusted for eosinophil counts (low vs. high), recipient age (≥50 vs. <50 years), aGVHD grade (III-IV vs. I-II), and stem cell source, the low eosinophil group showed independent poor prognosis for 1-year OS (HR, 6.0; 95% confidence interval, 1.3-28.4; p=0.023). Especially in patients with grade III-IV aGVHD, the low eosinophil group showed substantially inferior 1-year OS rates than those in the high eosinophil group (35.0% vs. 88.9%, p=0.032) (Figure B). Regarding secondary endpoints, 1-year PFS rates were 59.2% and 89.9% (p=0.006), 1-year CI rates of NRM were 21.7% and 3.33% (p=0.035), and 1-year CI rates of relapse were 19.1% and 6.8% (p=0.145) in the low and high eosinophil groups, respectively (Figures C-E).Conclusion: Low PB eosinophil counts before systemic corticosteroid therapy is associated with inferior 1-year OS after aGVHD due to elevated NRM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Revisiting characteristics, treatment and outcome of cardiomyopathy in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss).

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing eosinophil-rich vasculitis. Specific cardiomyopathy (CM) was described in early studies as the most important predictor of mortality. We aimed to revisit EGPA-related CM and investigate its outcome in recent decades. We reviewed all EGPA patients managed from 2000 to 2019 in our vasculitis clinic. Baseline characteristics and outcomes were analysed. EGPA-related CM was defined as clinical or extra-clinical manifestations of patent myocardial involvement, after exclusion of other causes. We included 176 patients. The median age was 47 years [interquartile range (IQR) 36-58 years]. Specific CM was observed in 70 patients (40%). Cardiac symptoms were observed in 81% of CM+ patients, including mainly typical or atypical chest pain and peripheral oedema. Abnormal ECG, transthoracic echocardiography and cardiac MRI (CMRI) were found in 72%, 72% and 99% of CM+ patients, respectively, contrasting with abnormalities in 32%, 38% and 60% of CM-negative patients, respectively. Late gadolinium enhancement (LGE) was the most frequent abnormality on CMRI (70%). CM+ patients were less frequently ANCA-positive, had less frequent peripheral neuropathy and had higher eosinophil count. Major adverse cardiovascular events (MACEs) occurred in 13% of patients, both in CM+ and CM- patients. Abnormal ECG and LGE on CMRI were associated with the occurrence of MACEs. Four patients died, but none from cardiac causes. Specific cardiomyopathy is frequent in EGPA, especially in ANCA-negative patients with high eosinophil counts. Long-term outcome was better than previously reported. Abnormal ECG and LGE on CMRI were associated with the occurrence of MACEs.