Lower Eosinophil Research Articles

Gaining insights into chronic obstructive pulmonary disease exacerbation through emerging biomarkers and the chronic obstructive pulmonary disease assessment test score.

Chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity, presents significant challenges, particularly with exacerbations, which drastically impact patients' health and healthcare costs. The Global Initiative for Chronic Obstructive Lung Disease guidelines recommend comprehensive assessments beyond spirometry, with the COPD assessment test (CAT) emerging as a pivotal tool. Despite its utility, the relationship between CAT scores and specific biomarkers during exacerbations remains unclear. Hence, this study aims to assess the correlation between the CAT score and specific circulating biomarkers. A cross-sectional study from August 2023 to January 2024 included 59 COPD patients with exacerbations who underwent pulmonary function tests and completed the CAT score assessment. The CAT score cut-off point was set at 20, where a CAT score <20 indicated a low impact on health status and a CAT score ≥20 indicated a high impact on health status. On the same day, measurements of neutrophils, leukocytes, eosinophils, C-reactive protein, and procalcitonin were conducted. Patients with CAT scores ≥20 had significantly higher levels of neutrophils (p=0.001), leukocytes (p=0.006), procalcitonin (p=0.010), and forced expiratory volume in the first second/forced vital capacity (p=0.002), but lower eosinophil levels (p=0.025). A positive correlation existed between total CAT score and neutrophils (p=0.001), leukocytes (p=0.000), and procalcitonin (p=0.010), while eosinophil levels showed a negative correlation (p=0.025). The spirometry parameters showed no correlation with the total CAT score. This study highlights the link between CAT and key inflammatory biomarkers, supporting the use of blood biomarkers to identify COPD patients at risk of exacerbations.

Relation between airway cellular and bacterial findings and severity of COPD exacerbations: A multicentric study

&lt;b&gt;Aim: &lt;/b&gt;To evaluate the relationships between sputum and bronchoalveolar lavage (BAL) cellular and bacterial findings and severity of exacerbation of chronic obstructive pulmonary disease (ECOPD).&lt;br /&gt; &lt;b&gt;Patients &amp;amp; methods: &lt;/b&gt;A cross-section study was conducted on 307 patients with ECOPD. They underwent sputum and BAL inflammatory cell count and bacterial culture.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; Patients with severe ECOPD have significantly higher neutrophils percentage (neut.%), lower lymphocytes percentage (lymph.%), lower eosinophils percentage (eosin.%) and higher neutrophil/lymphocyte ratio (NLR) as compared to patients with mild ECOPD. It was also shown that patients with severe ECOPD had significantly higher BAL neut.%, lower lymph.%, lower eosin.%, and higher NLR as compared to the other two subgroups. Also, patients with severe ECOPD have significantly higher frequency of cases with monomicrobial (71.30% vs. 36.10%) and polymicrobial (21.25% vs. 2.10%) growths in comparison to patients with mild ECOPD.&lt;br /&gt; &lt;b&gt;Conclusions: &lt;/b&gt;Cellular and bacterial findings in sputum and BAL are related to severity of ECOPD.

Eosinophilic bronchiectasis increases length and cost of hospitalization: a retrospective analysis in a hospital of southern China from 2012 to 2020

BackgroundThe concept of eosinophilic bronchiectasis has received clinical attention recently, but the association between blood eosinophil count (BEC) and hospital characteristics has rarely been reported yet. We aim to investigate the clinical impact of BEC on patients with acute bronchiectasis exacerbation.MethodsA total of 1332 adult patients diagnosed with acute exacerbation of bronchiectasis from January 2012 to December 2020 were included in this retrospective study. A propensity-matched analysis was performed by matching age, sex and comorbidities in patients with high eosinophil count (≥ 300 cell/µL) and low eosinophil count (< 300 cell/µL). Clinical characteristics, length of hospital stay (LOS), hospitalization cost and inflammatory markers were compared between the two groups.ResultsEosinophilic bronchiectasis occurred in approximately 11.7% of all patients. 156 propensity score–matched pairs were identified with and without high eosinophil count. Eosinophilic bronchiectasis presented with a longer LOS [9.0 (6.0–12.5) vs. 5.0 (4.0–6.0) days, p < 0.0001] and more hospitalization cost [15,011(9,753–27,404) vs. 9,109(6,402–12,287) RMB, p < 0.0001] compared to those in non-eosinophilic bronchiectasis. The median white blood cell (WBC), lymphocyte, platelet (PLT) and C-reactive protein (CRP) levels in eosinophilic bronchiectasis were significantly increased. Multivariate logistic regression analysis confirmed that the high levels of eosinophil count (OR = 13.95, p < 0.0001), worse FEV1% predicted (OR = 7.80, p = 0.0003) and PLT (OR = 1.01, p = 0.035) were independent prognostic factors for length of hospital (LOS) greater than 7 days.ConclusionEosinophilic bronchiectasis patients had longer length of hospital stay and more hospitalization cost compared to those in non-eosinophilic bronchiectasis group, which might be associated with the stronger inflammatory reaction.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6months of treatment. More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1month, 39% exhibited improvement at 6months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6months of treatment (OR and 95% CI 1.75 [1.09-2.98]). Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

Development and evaluation of a model for predicting the risk of healthcare-associated infections in patients admitted to intensive care units.

This retrospective study used 10 machine learning algorithms to predict the risk of healthcare-associated infections (HAIs) in patients admitted to intensive care units (ICUs). A total of 2,517 patients treated in the ICU of a tertiary hospital in China from January 2019 to December 2023 were included, of whom 455 (18.1%) developed an HAI. Data on 32 potential risk factors for infection were considered, of which 18 factors that were statistically significant on single-factor analysis were used to develop a machine learning prediction model using the synthetic minority oversampling technique (SMOTE). The main HAIs were respiratory tract infections (28.7%) and ventilator-associated pneumonia (25.0%), and were predominantly caused by gram-negative bacteria (78.8%). The CatBoost model showed good predictive performance (area under the curve: 0.944, and sensitivity 0.872). The 10 most important predictors of HAIs in this model were the Penetration Aspiration Scale score, Braden score, high total bilirubin level, female, high white blood cell count, Caprini Risk Score, Nutritional Risk Screening 2002 score, low eosinophil count, medium white blood cell count, and the Glasgow Coma Scale score. The CatBoost model accurately predicted the occurrence of HAIs and could be used in clinical practice.

Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts.

Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made. To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups. A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model. Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/μL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/μL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)]. Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.

A Low Eosinophil to Platelet Ratio as a Worse Prognostic Index for Emergency Department Attendance in Acute Exacerbation of COPD.

Identifying prognosis for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is challenging. Eosinophils and platelet are involved in the development of COPD, which may predict adverse events. The objective of this study was to determine the effect of the eosinophil to platelet ratio (EPR) in predicting adverse events in patients with AECOPD who visited the emergency department. The records of patients with AECOPD treated at Dalian Municipal Friendship Hospital from January 2018 to December 2020 were retrospectively reviewed. The relationship between the clinical characteristics and EPR, as cut-off value of 0.755, was evaluated. A total of 508 patients with an AECOPD (316 male, 192 female) were included. An optimal AUC cutoff of 0.755 for the EPR segregated the patients into 2 groups with significantly different mortality (25.3% vs 5.5%, P < 0.001). The same mortality risk with lower EPR was observed among the patients with emergency room attendance (35.6% vs 11.1%, P < 0.001). A model including EPR <0.755, exacerbation history, PaO2 <60mmHg, PaCO2 >50 mm Hg, hypoalbuminemia and age ≥80 was developed to predict death risk and showed good performance. During severe COPD exacerbation, an EPR < 0.755 preceding therapy can predict worse outcomes in patients with an AECOPD.

Protocol for the air purification for eosinophilic COPD study (APECS): a randomised controlled trial of home air filtration by HEPA

IntroductionExposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have...

Burden of Uncontrolled Severe Asthma With and Without Elevated Type-2 Inflammatory Biomarkers

Many patients with asthma have type-2 airway inflammation, identified by the presence of biomarkers, including history of allergy, high blood eosinophil (EOS) count, and high fractional exhaled nitric oxide levels. To assess disease burden in relation to type-2 inflammatory biomarker status (history of allergy, blood EOS count, and fractional exhaled nitric oxide level) in patients with uncontrolled and controlled severe asthma in the NOVEL observational longiTudinal studY (NOVELTY) (NCT02760329). Asthma diagnosis and severity were physician-reported. Control was defined using Asthma Control Test score (uncontrolled <20, controlled ≥20) and/or 1 or more severe physician-reported exacerbation in the previous year. Biomarker distribution (history of allergy, blood EOS count, and fractional exhaled nitric oxide level), symptom burden (Asthma Control Test score, modified Medical Research Council dyspnea scale), health status (St George's Respiratory Questionnaire score), exacerbations, and health care resource utilization were assessed. Of 647 patients with severe asthma, 446 had uncontrolled and 123 had controlled asthma. Among those with uncontrolled asthma, 196 (44%) had 2 or more positive biomarkers, 187 (42%) had 1 positive biomarker, 325 (73%) had low blood EOS, and 63 (14%) were triple-negative. Disease burden was similarly high across uncontrolled subgroups, irrespective of biomarker status, with poor symptom control (Asthma Control Test score 14.9-16.6), impaired health status (St George's Respiratory Questionnaire total score 46.7-49.4), clinically important breathlessness (modified Medical Research Council grade ≥2 in 47.3%-57.1%), and 1 or more severe exacerbation (70.6%-76.2%). Type-2 inflammatory biomarkers did not differentiate disease burden in patients with severe asthma. Patients with low type-2 inflammatory biomarker levels have few biologic therapy options; their needs should be addressed.

Association between low eosinophil count and acute bacterial infection, a prospective study in hospitalized older adults

BackgroundThe incidence of sepsis increases significantly with age, including a high incidence of bacterial infection in the old adults. Eosinopenia and the CIBLE score have been proposed in critically ill adults and in internal medicine wards. This study aimed to assess whether a low eosinophil count was associated with acute bacterial infection among hospitalized older adults, and to find the most efficient eosinophil count cut-off to differentiate acute bacterial infection from other inflammatory states.MethodsThis was a prospective study from July 2020 to July 2022 in geriatric wards of the University Paul Brousse Hospital (Villejuif, France) including patients aged of 75 y/o or over suffering from fever or biological inflammation. Acute bacterial infection was assessed using biological identification and/or clinical and radiological data.ResultsA total of 156 patients were included. Eighty-two (53%) patients suffered from acute bacterial infection (mean age (SD) 88.7 (5.9)). Low eosinophil count was independently associated with acute bacterial infection: OR [CI95%] 3.03 [1.04–9.37] and 6.08 [2.42–16.5] for eosinophil count 0–0.07 G/L and 0.07–0.172 G/L respectively (vs. eosinophil count > 0.172 G/L). Specificity and sensitivity for eosinophil count < 0.01 G/L and CIBLE score were 84%-49% and 72%-62%, respectively with equivalent AUCs (0.66 and 0.67).ConclusionEosinophil count < 0.01 G/L is a simple, routinely used and inexpensive tool which can easily participate in antibiotic decisions for older adults. Further studies are needed to assess clinical benefits.Trial registrationThe study was registered at Clinical trial.gov (NCT04363138–23/04/2020).

Pretreatment eosinophil count predicts response to atezolizumab plus bevacizumab therapy in patients with hepatocellular carcinoma.

Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). We enrolled 114 patients with u-HCC treated with ATZ/BEV (n=48) or lenvatinib (n=66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). Twenty-three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV-eosinophil-high group, which had better responses than the ATZ/BEV-eosinophil-low group (P=0.0090). Kaplan-Meier curves revealed a trend toward significantly better progression-free survival (PFS) in the ATZ/BEV-eosinophil-high group than the ATZ/BEV-eosinophil-low group (the median PFS: 4.7months in the ATZ/BEV-eosinophil-low group vs 12.6months in the ATZ/BEV-eosinophil-high group; P=0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P=0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02-4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV-eosinophil-high group (P=0.0285). The outcomes did not significantly differ between the LEN-eosinophil-high group and the LEN-eosinophil-low group. A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u-HCC and was associated with the incidence of AEs (≥ grade 3).

An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma

BackgroundAsthma is stratified into type 2-high and type 2-low inflammatory phenotypes. Limited success has been achieved in developing drugs that target type 2-low inflammation. Previous studies have linked IL-6 signaling to severe asthma. IL-6 cooperates with soluble-IL-6Rα to activate cell signaling in airway epithelium.ObjectiveWe sought to study the role of sIL-6Rα amplified IL-6 signaling in airway epithelium and to develop an IL-6+ sIL-6Rα gene signature that may be used to select asthma patients who potentially respond to anti-IL-6 therapy.MethodsHuman airway epithelial cells were stimulated with combinations of IL-6, sIL-6Rα, and inhibitors, sgp130 (Olamkicept), and anti-IL-6R (Tocilizumab), to assess effects on pathway activation, epithelial barrier integrity, and gene expression. A gene signature was generated to identify IL-6 high patients using bronchial biopsies and nasal brushes.ResultsSoluble-IL-6Rα amplified the activation of the IL-6 pathway, shown by the increase of STAT3 phosphorylation and stronger gene induction in airway epithelial cells compared to IL-6 alone. Olamkicept and Tocilizumab inhibited the effect of IL-6 + sIL-6Rα on gene expression. We developed an IL-6 + sIL-6Rα gene signature and observed enrichment of this signature in bronchial biopsies but not nasal brushes from asthma patients compared to healthy controls. An IL-6 + sIL-6Rα gene signature score was associated with lower levels of sputum eosinophils in asthma.ConclusionsIL-6Rα amplifies IL-6 signaling in bronchial epithelial cells. Higher local airway IL-6 + sIL-6Rα signaling is observed in asthma patients with low sputum eosinophils.

A Comparison of the Epidemiological Characteristics Between Influenza and COVID-19 Patients: A Retrospective, Observational Cohort Study.

Background and objective It is crucial to make early differentiation between coronavirus disease 2019 (COVID-19) and seasonal influenza infections at the time of a patient's presentation to the emergency department (ED). In light of this, this study aimed to identify key epidemiological, initial laboratory, and radiological differences that would enable early recognition during co-circulation. Methods This was a retrospective, observational cohort study. All adult patients presenting to our ED at the Watford General Hospital, UK, with a laboratory-confirmed diagnosis of COVID-19 (2019/20) or influenza (2018/19) infection were included in this study. Demographic, laboratory, and radiological data were collected. Binary logistic regression was employed to determinefeatures associated with COVID-19 infection rather than influenza. Results Chest radiographs suggestive of viral pneumonitis and older age (≥80 years) were associated with increased odds of having COVID-19 [odds ratio (OR): 47.00, 95% confidence interval (CI): 21.63-102.13and OR: 64.85, 95% CI: 19.96-210.69respectively]. Low eosinophils (<0.02 x 109/L) were found to increasethe odds of COVID-19 (OR: 2.12, 95% CI: 1.44-3.10, p<0.001). Conclusions Gaining awareness about the epidemiological, biological, and radiologic presentation of influenza-like illness can be useful for clinicians in ED to differentiate between COVID-19 and influenza. This study showed that older age, eosinopenia, and radiographic evidence of viral pneumonitis significantly increase the odds of having COVID-19 compared to influenza. Further research is needed to determine if these findings are affected by acquired or natural immunity.

Cross-sectional and longitudinal relationships between complete blood count measures and adolescent suicidal behavior

ObjectiveReplicable biological predictors are needed to distinguish adolescents at risk for suicide attempts (SA) compared to those at risk for suicidal ideation (SI). Early evidence in adults identifies that complete blood count (CBC) measures may be directly related to suicidal behavior (SB). MethodsIn this retrospective chart review, we assessed if CBC measures differed between adolescents psychiatrically hospitalized for SA versus SI, initially in an exploratory test cohort (n = 110, age = 11–18, 67 % female, 72.7 % White) and then in an independent confirmatory replication cohort (n = 97). In longitudinal analyses, we identified if CBC measures predicted future SB over 90 days. CBC measures were also compared to a healthy adolescent cohort (n = 597) and a medically-hospitalized nonsuicidal adolescent cohort (“MH” cohort; n = 51). ResultsSuicide attempters had lower eosinophil percentages, eosinophil counts, and platelet counts as compared to suicide ideators, though in the replication cohort, only eosinophil percentages were lower in suicide attempters. In longitudinal analysis, both lower eosinophil blood counts and percentages were associated with future suicidal behavior. In cross-sectional comparative analyses, the MH cohort had similar or lower eosinophil percentages/counts to adolescents psychiatrically hospitalized with SA. ConclusionsThough lower eosinophil percentages and counts were present in adolescents with recent SA (compared to SI), such effects may be related to physical sequalae of SA. Nevertheless, both lower eosinophil counts and percentages appear to be valuable predictors of prospective suicidal behavior over 90 days amongst psychiatrically hospitalized adolescents. These findings may guide research seeking to effectively identify adolescents at elevated risk of future suicide attempts.

Serum α-Klotho level, lung function, airflow obstruction and inflammatory markers in US adults.

α-Klotho is a pleiotropic protein that may have anti-oxidative and anti-inflammatory properties in the lung, but its role in airflow obstruction or lung function is largely unknown. This was a cross-sectional study of 6046 adults aged 40-79 years in the US National Health and Nutrition Examination Survey (NHANES) 2007-2012. We used multivariable logistic or linear regression to examine the relation between serum α-Klotho level and airflow obstruction, defined as forced expiratory volume in 1 s (FEV1) <80% of predicted and FEV1/forced vital capacity (FVC) ratio <0.70; FEV1, FVC and FEV1/FVC as percentage of predicted; and inflammatory markers in blood (white blood cell count, eosinophils, neutrophils and C-reactive protein (CRP)). α-Klotho levels in the second to fourth quartiles (Q2-Q4) were associated with significantly decreased odds of airflow obstruction (adjusted OR for Q2-Q4 versus lowest quartile (Q1) 0.54 (95% CI 0.35-0.81)) in never-smokers and ex-smokers with <10 pack-years of smoking, but not in current smokers or ex-smokers with ≥10 pack-years of smoking. In all participants, each unit increment in log10-transformed α-Klotho level was significantly associated with 5.0% higher FEV1 % pred and 3.7% higher FVC % pred. Higher α-Klotho was also associated with lower eosinophils, neutrophils and CRP in participants both with and without airflow obstruction. Higher serum α-Klotho is associated with lower inflammatory markers and higher lung function in adults with and without airflow obstruction, and with decreased odds of airflow obstruction in never-smokers and ex-smokers with <10 pack-years of smoking. Further studies are warranted to replicate our findings and evaluate underlying mechanisms.

Exhaled nitric oxide, eosinophils and current smoking in COPD patients.

High FENO can occur despite low blood eosinophil counts in ex-smokers, while a minority of current smokers have elevated FENO that is not related to eosinophil counts. FENO levels may be related to noneosinophilic mechanisms in a subgroup of COPD. https://bit.ly/3PSWvM2.

Predictors of persistent disease in biologic treated type 2 diffuse/eosinophilic chronic rhinosinusitis undergoing surgery.

Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control. A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control. A total of 37 patients were included (age 47.8±12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3%vs. 50.0%, p<0.001) and increased serum neutrophils (5.2±2.7vs. 3.7±1.1×109 cells/L, p=0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR=0.21, 95% CI [0.05, 0.83], p=0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75×109 cells/L (sensitivity=80.0%, specificity=96.9%, AUC=0.938, p=0.002). Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75×109 cells/L predicts for poor response to current biologic therapy.

Histopathologic features of biologic therapy nonresponders in chronic rhinosinusitis with nasal polyposis.

Biologics are effective for chronic rhinosinusitis with nasal polyposis (CRSwNP) by reducing type 2 inflammation. Nonresponders often require functional endoscopic sinus surgery (FESS) and represent a challenging population potentially due to non-type 2 pathophysiology. This study characterizes the histopathologic features of biologic nonresponders. A retrospective review of 257 CRSwNP patients undergoing FESS was conducted. The biologic nonresponder group included patients with prior biologic therapy who exhibited persistent symptoms and polyp burden. Those with CRSwNP not prescribed biologic therapy were selected as controls. Demographics, comorbidities, and structured histopathology consisting of 13 variables were collected. Of 257 CRSwNP patients, 20 were on biologics prior to FESS. Fourteen patients (70.0%) received dupilumab, one (5.0%) received mepolizumab, one (5.0%) received omalizumab, and four (20.0%) tried multiple biologics. The mean age for the biologic nonresponder group was 45.8 years compared to 50.4 years for the controls. Nonresponders had a significantly increased incidence of reduced tissue eosinophilia, defined as<5 per high power field (55%vs. 31.2%, p=0.044) and increased basement membrane thickening (100%vs. 78.1%, p=0.019). The remaining 11 variables did not reach statistical significance. Histopathologic analysis of biologic nonresponders demonstrates decreased eosinophilia and thickened basement membranes. These findings, particularly low tissue eosinophils, are consistent with a non-type 2 CRSwNP that may be recalcitrant to biologic therapies. Histopathologic analysis done in conjunction with FESS may aid clinicians in understanding response to biologic therapies in patients with CRSwNP who have persistent symptom burden necessitating FESS.

The role of first trimester eosinophil count and eosinophil-based complete blood cell indices in the predictiction of preeclampsia: A case-control study

IntroductionThe importance of eosinophils in the pathogenesis of preeclampsia is an question of interest and there are recent studies in the literature indicating significantly lower eosinophil count values in pregnant women with preeclampsia. The present study aims to evaluate the utility of first-trimester eosinophil count and eosinophil-based complete blood cell count indices in the prediction of preeclampsia. MethodsPregnant women diagnosed with preeclampsia (n = 281) were retrospectively compared with a control group (n = 307). The utility of first trimester eosinophil count, neutrophil to eosinophil ratio (NER) (neutrophil/eosinophil), leukocyte to eosinophil ratio (LER) (leukocyte/eosinophil), eosinophil to monocyte ratio (EMR) (eosinophil/monocyte) and, eosinophil to lymphocyte ratio (ELR) (eosinophil/lymphocyte) in the prediction of preeclampsia were evaluated. ResultsOptimal cut-off values for eosinophil count, NER, LER, EMR and, ELR in predicting preeclampsia were 0.07 (AUC: 0.62, 58.7% sensitivity, 56.4% specificity), 90.9 (AUC: 0.65, 61.1% sensitivity, 59.4% specificity), 125.7 (AUC: 0.64, 61.4% sensitivity, 58.4% specificity), 0.15 (AUC: 0.63, 60.1% sensitivity, 59.6% specificity) and, 0.03 (AUC: 0.62, 60.9% sensitivity, 57% specificity), respectively. Mentioned values in predicting early-onset preeclampsia were 0.07 (AUC: 0.64, 60.5% sensitivity, 50.8% specificity), 102.1 (AUC: 0.64, 62.4% sensitivity, 58.8% specificity), 140.2 (AUC: 0.65, 63.5% sensitivity, 59.1% soecificity), 0.14 (AUC: 0.66, 66.3% sensitivity, 59.2% specificity), and, 0.03 (AUC: 0.63, 60.5% sensitivity, 57.4% specificity), respectively. The optimal cut-off value for EMR in the prediction of preeclampsia with severe features was 0.16 (AUC: 0.56, 56.9% sensitivity, 53.2% specificity). DiscussionEosinophil-based complete blood count indices may be used to predict early-onset preeclampsia with relatively low sensitivity and specificity.

Airway inflammatory changes in the lungs of patients with asthma-COPD overlap (ACO): a bronchoscopy endobronchial biopsy study

BackgroundAlthough asthma and chronic obstructive pulmonary disease (COPD) are two distinct chronic airway inflammatory diseases, they often co-exist in a patient and the condition is referred to as asthma-COPD overlap (ACO). Lack of evidence regarding the inflammatory cells in ACO airways has led to their poor prognosis and treatment. The objective of this endobronchial biopsy (EBB) study was to enumerate inflammatory cellular changes in the airway wall of ACO compared with asthma, COPD current smokers (CS) and ex-smokers (ES), normal lung function smokers (NLFS), and non-smoker controls (HC).MethodsEBB tissues from 74 patients were immunohistochemically stained for macrophages, mast cells, eosinophils, neutrophils, CD8+ T-cells and CD4+ T-cells. The microscopic images of stained tissues were evaluated in the epithelium, reticular basement membrane (RBM) cells/mm RBM length, and lamina propria (LP) cells/mm2 up to a depth of 120 µM using the image analysis software Image-Pro Plus 7.0. The observer was blinded to the images and disease diagnosis. Statistical analysis was performed using GraphPad Prism v9.ResultsThe tissue macrophages in ACO were substantially higher in the epithelium and RBM than in HC (P < 0.001 for both), COPD-ES (P < 0.001 for both), and -CS (P < 0.05 and < 0.0001, respectively). The ACO LP macrophages were significantly higher in number than COPD-CS (P < 0.05). The mast cell numbers in ACO were lower than in NLFS (P < 0.05) in the epithelium, lower than COPD (P < 0.05) and NLFS (P < 0.001) in RBM; and lower than HC (P < 0.05) in LP. We noted lower eosinophils in ACO LP than HC (P < 0.05) and the lowest neutrophils in both ACO and asthma. Furthermore, CD8+ T-cell numbers increased in the ACO RBM than HC (P < 0.05), COPD-ES (P < 0.05), and NLFS (P < 0.01); however, they were similar in number in epithelium and LP across groups. CD4+ T-cells remained lower in number across all regions and groups.ConclusionThese results suggest that the ACO airway tissue inflammatory cellular profile differed from the contributing diseases of asthma and COPD with a predominance of macrophages.