Eosinophil Count Research Articles

Worse lung function, more allergic sensitization but less blood eosinophilia in elderly patients with long-standing versus late-onset asthma

ABSTRACT Background Asthma in the elderly is usually considered homogeneous and non-atopic. Objective To compare clinical, functional and immunological features between elderly asthmatics with long-standing asthma (LSA) and those with late-onset asthma (LOA). Methods Eighty-two asthmatics older than 64 were included into LSA (asthma onset before age 40; n =46) and LOA (asthma onset from 40 years of age on; n = 36) groups. Asthma treatment and comorbidities were recorded. All individuals underwent the asthma control questionnaire-7 (ACQ-7) and cognitive impairment screening (Mini-Mental State Examination). Inhaler technique was assessed by checklists; the Morisky Medication Adherence Scale-8 was used to assess adherence to treatment. Spirometry, skin prick tests (SPTs), induced sputum and blood eosinophil counts were performed. Results We found high frequencies of cognitive impairment, poor inhaler technique and low adherence to treatment in both groups, which had good disease control (ACQ-7 scores: 1.20 ± 0.74 versus 1.11 ± 0.89; p = 0.67, respectively). The LSA group had more severe airway obstruction (FEV1(% predicted): 62.04 ± 19.50 versus 77.15 ± 18.74, p< 0.01; FEV1/FVC: 0.59 ± 0.10 versus 0.69 ± 0.09, p < 0.01); higher frequency of positive SPTs (65.6% versus 18.8%, p = 0.001); and lower frequency of blood eosinophilia (45.7% versus 77.1%, p = 0.004) than the LOA group. No differences in sputum cell counts or inflammatory profiles were found between the groups. Ninety percent of the individuals studied had at least one feature of Type 2 asthma. Conclusion LSA and LOA phenotypes differ substantially. That should be accounted for in research and clinical practice grounds.

Symptomatic Improvement in Adults and Adolescents with Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure than Histologic Response.

We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications. Results for the phase 3 LIBERTY EoE TREET study co-primary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses. A steep initial relationship then plateau was observed between higher dupilumab steady state trough concentrations (Ctrough) and decreased eosinophilic infiltration at Week 24, while a graded exposure-response relationship was observed for symptomatic improvement at Week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation. The dupilumab 300 mg qw regimen approved for adults and adolescents with EoE weighing ≥40 kg is supported by dose- and exposure-response relationships.

Longitudinal multi-trajectory phenotypes of severe eosinophilic asthma on type 2 biologics treatment

BackgroundLimited understanding exists regarding the progression trajectory of severe eosinophilic asthma (SEA) patients on type 2 biologics therapies. ObjectiveWe aim to explore distinct longitudinal phenotypes of these patients based on crucial asthma biomarkers. MethodsWe enrolled 101 adult patients with SEA. Of these, 51 were treated with anti-IL5/IL5Rα or anti-IL5/IL5RαR antibody, and 50 with anti-IL-4Rα antibody. Multi-trajectory analysis, an extension of univariate group-based trajectory modeling, was used to categorize patients based on their trajectories of forced expiratory volume in 1 s (FEV1), blood eosinophil counts (BEC), and fractional exhaled nitric oxide (FeNO) levels at baseline, and after 1, 6, and 12 months of treatment. Associations between trajectory-based clusters and clinical parameters were examined. ResultsAmong anti-IL5/IL5Rα antibody-treated patients, 2 clusters were identified. The cluster characterized by higher baseline BEC and lower FEV1 showed a better response, with improvements in FEV1 and reductions in BEC over time. Among anti-IL-4Rα antibody-treated, 3 clusters were identified. Clusters with moderate BEC and FeNO at baseline demonstrated better improvements in FEV1 and reductions in FeNO, despite increased BEC during follow-up. Conversely, individuals with extremely low FeNO and high BEC at baseline were more likely to experience poorer progression, demonstrating an increase in FeNO and a reduction in FEV1. ConclusionTo optimally monitor treatment response in SEA patients on type 2 biologics, integrating longitudinal biomarker features is essential.

Effectiveness of benralizumab in the Tokyo Asthma Study (TOAST): A real-world prospective interventional trial

BackgroundBiologics are integral in the management of severe asthma. As the effectiveness of the anti-IL-5 receptor antibody benralizumab in Japan remains elusive, this study aimed to assess its real-world effectiveness in Japanese patients with severe asthma. MethodsThis prospective, interventional, single-arm clinical trial was conducted across ten facilities in Japan between September 2020 and July 2022. Adult patients with severe eosinophilic asthma (peripheral blood eosinophil count ≥150 cells/μl) were enrolled and treated with benralizumab. The primary endpoint was the change in ACQ-5 score from baseline to week 24. ResultsOf 103 patients, 98 (mean age: 62.1 years, women: 55.1 %, regular oral corticosteroids [OCS] treatment: 20.4 %) were included in the analysis. From baseline to week 24, benralizumab significantly improved ACQ-5 (−0.67, 95 % CI: −0.94 to −0.39) and AQLQ (0.71, 95 % CI: 0.46 to 0.96) scores with an increase in FEV1 (87 ml, 95 % CI: 15–159 ml). The maintenance OCS dose and the percentage of OCS users decreased from 13.9 mg/day to 6.0 mg/day and from 20.4 % to 9.2 %, respectively. Multivariable analysis identified baseline blood eosinophil count (≥400 cells/μl) and fractional exhaled nitric oxide (≥22 ppb) as independent predictors of therapeutic response to benralizumab. Benralizumab treatment was discontinued due to nonserious adverse events and patient choice in four and three patients, respectively. ConclusionsIn a real-world setting in Japan, patients with severe eosinophilic asthma treated with benralizumab demonstrated substantial improvements in asthma control, quality of life, and respiratory function with reduced OCS usage. Trial registration: Japan Registry of Clinical Trials (jRCTs031190237).

Osteopontin as a Novel Biomarker in Distinguishing Chronic Rhinosinusitis with Nasal Polyp Endotypes and Predicting Disease Severity

Introduction: The objective of this study was to ascertain the predictive value of osteopontin (OPN), a cytokine with pro-inflammatory properties implicated in inflammatory and allergic conditions, in nasal secretions for the identification of chronic rhinosinusitis with nasal polyp (CRSwNP) endotypes and the assessment of disease severity. Methods: A cohort comprising 81 individuals diagnosed with CRSwNP was enrolled, which included 37 subjects with the non-eosinophilic CRSwNP and 44 subjects with the eosinophilic CRSwNP (eCRSwNP), alongside 32 healthy controls (HCs). Nasal secretions and tissue samples were collected from all participants. The quantification of OPN in these samples was conducted using ELISA and immunohistochemistry. Nasal fractional exhaled nitric oxide levels were determined with the Nano Coulomb Breath Analyzer. The diagnostic efficacy of OPN levels in distinguishing eCRSwNP was assessed using the receiver operating characteristic (ROC) curve, while Pearson correlation analysis was employed to evaluate the correlation between OPN levels and disease severity indicators. Results: Concentrations of OPN in nasal secretions were found to be elevated in CRSwNP patients compared to the HC group and significantly higher in patients with eCRSwNP. A positive correlation was identified between OPN levels in nasal secretions and peripheral blood eosinophil counts and percentages, and tissue eosinophil counts, as well as the Visual Analog Scale (VAS) score, Lund-Mackay score, and Lund-Kennedy score. The ROC analysis demonstrated that the OPN level in nasal secretions possesses a robust discriminatory capacity for eCRSwNP, with a cutoff value of 121.05 ng/mL. Furthermore, the OPN concentration was determined to be a more precise predictor of the VAS score, Lund-Mackay score, and Lund-Kennedy score than the CRSwNP endotypes. Conclusion: The findings of this study indicate that OPN is differentially expressed in the nasal secretions of eCRSwNP patients and correlates with eosinophilic inflammation. The presence of OPN in nasal secretions emerges as a novel and potentially valuable biomarker for the differentiation of CRSwNP endotypes and the prognostication of disease severity.

Association Between Serum Vitamin D Level and Uncontrolled Chronic Rhinosinusitis With Nasal Polyposis.

Objective: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by type 2 inflammation, and studies have shown that conventional therapy usually yields unsatisfactory results. While recent studies have indicated the potential effect of vitamin D on allergic and inflammatory diseases, including CRSwNP. Therefore, this study aimed to investigate the relationship between serum vitamin D levels and the severity of CRSwNP using endoscopic evaluations, imaging, patient-reported outcome measures, absolute eosinophilic count, and serum vitamin D levels and determine the prevalence of vitamin D deficiency in patients with CRSwNP. Methods: Serum vitamin D levels were measured in 104 patients with uncontrolled CRSwNP, who failed maximum medical management and were scheduled for functional endoscopic sinus surgery. Vitamin D levels were compared between patients using the Lund- Mackay (LM) score, Sinonasal Outcome Test-22 (SNOT-22), total nasal polyp scores, and absolute eosinophil counts. Results: The 104 included patients had an average age of 42.09 ± 13.3 years, and 63.5% of them were male. Mean value of vitamin D was 57.9 ± 31.2 nmol/L. The average SNOT-22 score was 65.49 ± 21.3. The mean LM score was 14.48 ± 6.64. The total nasal polyp score was 4.3 ± 2.08. Vitamin D levels were negatively correlated with LM score (r = -.210, P = .032) and polyp grade (r = -.264, P = .007), but did not correlate with other variables. Conclusions: Our study indicates that vitamin D deficiency or insufficiency is common in patients with CRSwNP. We found that low serum vitamin D levels were negatively correlated with the Lund-Mackay score and the total nasal polyp score, providing additional support for an association between low vitamin D levels and a greater severity of CRSwNP.

Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial

Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are important events and are associated with critical illness. Eosinophilic inflammation is a treatable trait commonly found during acute exacerbations of asthma and COPD. We hypothesised that for patients with eosinophilic exacerbations, a single injection of benralizumab, a humanised monoclonal antibody against interleukin-5 receptor-α, alone or in combination with prednisolone, will improve clinical outcomes compared with prednisolone, the standard of care. The Acute exacerbations treated with BenRAlizumab trial (ABRA) was a multicentre, phase 2, double-blind, double-dummy, active placebo-controlled randomised trial completed in the UK at Oxford University Hospitals NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust. Patients were recruited from urgent care clinics and emergency departments of these two hospitals. At the time of an acute exacerbation of asthma or COPD, adults with blood eosinophil counts of equal to or more than 300 cells per μL were randomly assigned in a 1:1:1 ratio to receive acute treatment with: prednisolone 30 mg once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA plus PRED group); placebo tablets once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA group); or prednisolone 30 mg once daily for 5 days and placebo subcutaneous injection once (PRED group). Randomisation was performed with a centralised interactive computer randomisation service. All patients and study research staff involved in data collection were masked to study blood results and treatment allocation. The co-primary outcomes were proportion of treatment failures over 90 days and total visual analogue scale (VAS) symptoms at day 28 in the pooled benralizumab groups compared with the prednisolone alone group and analysed in the intention-to-treat population. The trial was registered on Clinicaltrials.govNCT04098718. Between May 13, 2021, and Feb 5, 2024, 287 patients were screened for study inclusion. 129 were excluded due to not having an exacerbation captured or not meeting the eosinophil exclusion criteria. 158 patients were randomly assigned at acute eosinophilic exacerbation of asthma or COPD where 86 (54%) patients were female and 72 (46%) were male with a mean age of 57 years (range, 18-84). 53 patients were randomly assigned to the PRED group, 53 were randomly assigned to the BENRA group, and 52 were assigned to the BENRA plus PRED treatment group. At 90 days, treatment failures occurred in 39 (74%) of 53 in the PRED group, and 47 (45%) of 105 in the pooled-BENRA group (OR 0·26 [95% CI 0·13-0·56]; p=0·0005). The 28-day total VAS mean difference was 49 mm (95% CI 14-84; p=0·0065), favouring the pooled-BENRA group. There were no fatal adverse events and benralizumab was well tolerated. Notably, hyperglycaemia and sinusitis or sinus infection adverse events were related to the prednisolone study drug only. Benralizumab can be used as a treatment of acute eosinophilic exacerbations and achieves better outcomes than the current standard of care with prednisolone alone. These results offer a new way of treating eosinophilic endotypes of asthma and COPD exacerbations. AstraZeneca.

Exploring hematological diversity, a comprehensive study of CBC variations among the population of Tehsil Kot-Momin Sargodha

Objectives: To ascertain the diversity and patterns observed in the complete blood count within the population of Tehsil Kot-Momin , Sargodha. Study Design: Observational Cross Sectional Study Place of Study: Rai Medical College,Sargodha Materials &amp; Methods: A comprehensive collection of 401 CBC samples was meticoulously acquired from individuals at Medina Medical Complex in Kot-Momin ,Sargodha, subsequent to securing verbal informed consent. Subsequent research activities were conducted at Rai Medical College,Sargodha, post-recipt of sanction from the institutional ethical review committee. The time frame for data accumulation extended from june 2023 through August 2023 and the results were analyzed on SPSS Ver 27. Results: The study aimed to explore gender differences in hematological parameters among a sample of 401 individuals. Key findings indicated significant gender-based variations in hemoglobin (p &lt; 0.001), total RBC count ( p&lt; 0.001), hematocrit (p &lt;0.001) , platlelt count (p=0.008), and mean platelet volume (MPV) (p=0.033). In this investigation, male subjects were observed to possess higher mean concentration of hemoplobin , total erythrocyte count and hematocrit levels relative to their female counterparts, who demonstrated an augmented mean thrombocyte count. Significantly, the mean thrombocyte volume (MTV)-a proxy for platelet volume - was markedly distinct between genders, alluding to potential differences in thrombocyte function or production. Conversly, the study revealed no statistically significant disparities in parameters such as leukocyte count (WBC) , mean corpuscular volume ( MCV), mean corpuscular hemoglobin (MCH) , mean corpuscular hemoglobin concentration (MCHC), and proportions of hematocrit (PCT), as well as neutrophil,lymphocyte ,monocyte, eosinophil and basophil counts, thereby indicating a homogeneity in these hematological indices across genders. Conclusion: This study offers a comprehensive analysis of variations in hematological parameters across different groups, highlighting significant differences in hemoglobin , total RBC count, hematocrit, platelet count and mean platelet volume. These findings underscore the potential influence of biological and physiological factors on blood profiles, suggesting a need for personalized approaches in the interpretation of hematological data for clinical or diagnostic purposes.

Role of Monoclonal Antibodies in the Management of Eosinophilic COPD: A Meta-analysis of Randomized Controlled Trials.

COPD remains a leading cause of morbidity and mortality worldwide. Acute exacerbations are associated with progressive decline in lung function and quality of life. After recognition of the role of type 2 inflammation in the pathogenesis of eosinophilic COPD, there was increased interest in studying monoclonal antibodies as a therapeutic agent. Multiple randomized control trials (RCTs) showed promising results, yet no consensus exist. Our study aims to summarize the current evidence regarding the role of monoclonal antibodies in the management of patients with eosinophilic COPD. We systematically searched multiple databases using pre-specified search terms. We included only RCTs comparing monoclonal antibodies to placebo in patients with objective evidence of eosinophilic COPD receiving standard of care. The primary outcome of interest was annualized rate of COPD exacerbation. Absolute changes in FEV1, and SGRQ scores were secondary outcomes. We also reported serious adverse effects and all-cause mortality. Statistical analysis was conducted via random effects model, using RevMan software. We identified and included 8 double blinded, placebo-controlled trials with a total of 4,512 patients, and a median follow up of 52 weeks. The patients mean age was 65±8 years, with 85% male majority. 70% of patients were former smokers, with a mean of 43±25 pack-years. The majority of patients were on triple inhaled therapy. The mean serum eosinophil count on enrollment was 398±297 cell/µL. Monoclonal antibodies were Dupilumab, Mepolizumab, Benralizumab, Astegolimab, and Itepekimab. Compared to placebo, patients who received monoclonal antibody had a significantly decreased annualized COPD exacerbation rate [RR 0.79; 95% CI (0.73, 0.86), P<0.001]. The serious adverse effect rate was significantly lower in monoclonal antibody arm compared to placebo, [OR 0.80, 95% CI (0.69, 0.93, P=0.004)]. All-cause mortality rate was not statistically different between the groups, [OR of 0.91, 95% CI (0.63, 1.3, P=0.6)]. Dupilumab showed a trend of efficacy over Mepolizumab and Benralizumab. In patients with eosinophilic COPD receiving standard of care therapy, the use of monoclonal antibodies led to a significant reduction in annualized COPD exacerbation rate compared to placebo. Monoclonal antibodies have an acceptable tolerability and safety profile.

Prospective study on the association between 36 human blood cell traits and pan-cancer outcomes: a mendelian randomization analysis

BackgroundResearch on the link between blood cell traits and cancer risk has gained significant attention. Traditional epidemiological and cell biology studies, have identified correlations between blood traits and cancer risks. These findings are important as they suggest potential risk factors and biological mechanisms. However, these studies often can’t confirm causality, pointing to the need for further investigation to understand these relationships better.MethodsMendelian randomization (MR), utilizing single-nucleotide polymorphisms as instrumental variables, was employed to investigate blood cell trait causal effects on cancer risk. Thirty-six blood cell traits were analyzed, and their impact on 28 major cancer outcomes was assessed using data from the FinnGen cohort, with eight major cancer outcomes and 22 cancer subsets. Furthermore, 1,008 MR analyses were conducted, incorporating sensitivity analyses (weighted median, MR-Egger, and MR-PRESSO) to address potential pleiotropy and heterogeneity.ResultsThe analysis (data from 173,480 individuals primarily of European descent) revealed significant results. An increase in eosinophil count was associated with a reduced risk of colorectal malignancies (OR = 0.7702 per 1 SD higher level, 95% CI = 0.6852 to 0.8658; P = 1.22E-05). Similarly, an increase in total eosinophil and basophil count was linked to a decreased risk of colorectal malignancies (OR = 0.7798 per 1 SD higher level, 95% CI = 0.6904 to 0.8808; P = 6.30E-05). Elevated hematocrit (HCT) levels were associated with a reduced risk of ovarian cancer (OR = 0.5857 per 1 SD higher level, 95% CI = 0.4443 to 0.7721; P = 1.47E-04). No significant heterogeneity or horizontal pleiotropy was observed.ConclusionsOur study highlights the complex and context-dependent roles of blood cell traits in cancers.

Leptin augments IL-13-induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma

BackgroundAirway tissue eosinophilia can be an observed feature of obesity associated T2 asthma, but the processes mediating this inflammation are unknown. ObjectiveWe investigated a process whereby leptin, an adipokine elevated in obesity, potentiates pulmonary eosinophilia and eotaxin production by airway fibroblasts in T2 asthma. MethodsWe assessed associations between body mass index and airway eosinophilia, leptin and eotaxin production in 78 asthma participants, 36 of which exhibited obesity. Cultured human airway fibroblasts and mouse models of chronic allergic airway disease were used to evaluate leptin’s effect on eotaxin production and lung eosinophilia. The role of interleukin-13 receptor alpha 2 (IL-13Rα2) in mediating these processes was examined using specific neutralizing antibodies in vitro. ResultsIn T2 asthma participants with obesity, we observed that airway tissue eosinophilia did not associate with traditional T2 inflammation metrics such as peripheral and/or bronchoalveolar lavage fluid (BALF) eosinophil counts or with fractional concentration of exhaled nitric oxide (FeNO). Alternatively, we observed elevated BALF leptin and eotaxin-1 levels. In airway fibroblasts from asthma participants, leptin augmented IL-13-induced eotaxin-1 and -3 production and IL13RA2 expression. In mice, elevated leptin promoted airway IL-13Rα2 and eotaxin production by lung fibroblasts and lung tissue eosinophilia following chronic house dust mite allergen exposure. Inhibition of IL-13Rα2 reduced combined leptin and IL-13-stimulated eotaxin secretion by human airway fibroblasts. ConclusionWe identified a potential association explaining airway tissue eosinophil retention in obesity-associated T2 asthma through leptin-mediated enhancement of IL-13-induced eosinophil chemokine production by airway fibroblasts, a process requiring IL-13Rα2.

Association of asthma and bronchiectasis: Mendelian randomization analyses and observational study

BackgroundPrevious studies have demonstrated that asthma is closely associated with bronchiectasis, however, the causal relationship between asthma and bronchiectasis has not been investigated in depth. Therefore, this study aims to explore the causal relationship and to identify potential factors that mediate between these two diseases.MethodAll the necessary summarized information were obtained from publicly available genome-wide association study (GWAS). Two-sample Mendelian randomization (two-sample MR) was employed to explore the causal relationship between asthma and bronchiectasis, with an additional dataset used for validation. Heterogeneity and pleiotropy analyses were utilized to verify the robustness of the results. Subsequently, mediation MR analyses were performed to identify potential mediating factors. Lastly, a retrospective observational study was conducted to validate the findings.ResultPreliminary inverse-variance weighted (IVW) results indicated there was a causal effect of asthma on bronchiectasis (odds ratio [OR] = 1.228, 95% confidence interval [CI]: 1.077–1.400, P = 0.002). Repetition validation yielded a consistent result. Mediation MR analysis demonstrated that the presence of nasal polyps (OR = 1.063, 95% CI: 1.015–1.113, mediation ratio = 30.492%, P = 0.009), acute sinusitis (OR = 1.062, 95% CI: 1.009–1.118, mediation ratio = 30.157%, P = 0.018), chronic sinusitis (OR = 1.085, 95% CI: 1.024–1.150, mediation ratio = 40.677%, P = 0.005), and peripheral eosinophil counts (OR = 1.013, 95% CI: 1.000–1.026, mediation ratio = 6.514%, P = 0.042) served as significant mediators in the occurrence and development of bronchiectasis induced by asthma. Furthermore, a retrospective observational study observed that bronchiectasis patients with asthma had a higher prevalence of sinusitis (5.043% vs 2.971%, P < 0.001), nasal polyps (0.536% vs 0.152%, P < 0.001), and rhinitis (13.197% vs 1.860%, P < 0.001). The ratio (1.950 (0.500, 5.600) vs 1.500 (0.500, 2.600), P = 0.006) and counts (0.125 (0.040, 0.363) vs 0.090 (0.030, 0.160), P < 0.001) of peripheral blood eosinophils were also elevated in bronchiectasis patients with asthma.ConclusionThe MR analysis uncovered a notable genetic association between asthma and bronchiectasis, which was partially mediated by sinusitis, nasal polyps, and eosinophils. A subsequent retrospective study provided further evidence by demonstrating that bronchiectasis patients with asthma had a higher prevalence of sinusitis, nasal polyps, an elevated proportion of eosinophils, and higher eosinophil counts.

The Effects of Mepolizumab on CRSwNP: Real-Life Evidence.

Background: This study aims to evaluate the efficacy and safety of mepolizumab in the treatment of severe uncontrolled CRSwNP with or without comorbid asthma in a real-life setting over the first six months of therapy. Methods: A total of 45 patients with nasal polyps with or without comorbid asthma were treated with mepolizumab (100 mg q4w) for 6 months. The following outcomes were assessed before therapy (V0), and after 6 months (V1): endoscopic nasal polyp score (NPS), nasal congestion score (NCS), sinonasal outcome test (SNOT-22), visual analog scale (VAS), nasal flow rate (PNIF), olfactory test (SS-I), and asthma control test (ACT). Blood eosinophil count, oral steroid intake, and rescue surgery were also measured. Results: We found a statistically significant improvement in NPS, NCS, SNOT-22, overall VAS, PNIF, SS-I, and ACT. In addition, we observed a decrease in blood eosinophils count. Mepolizumab was well tolerated, and no patients interrupted the treatment during the follow up. Conclusions: Our real-life study confirmed the efficacy and tolerance of mepolizumab prescribed for CRSwNP with or without asthma. The safety profile of mepolizumab was consistent with previous reports.

Altered leukocyte pattern and inflammatory markers in unvaccinated long covid patients: a cross-sectional study.

Long Covid results from the damage caused by SARS-CoV-2, involving the release of cytokines and the continuous activation of immune cells. This cross-sectional study investigates leukocyte and cytokine profiles in Long Covid patients in the Amazon, a region where such studies are limited. Blood samples were analysed for differential leukocyte counts and cytokine levels. We suggest elevated lymphocyte counts in hospitalised patients and those with severe COVID-19. Higher eosinophil counts were observed in patients with up to three months of Long Covid, and increased monocyte counts in those with up to six months. IL-2 levels were higher in patients with fewer symptoms and Long Covid duration of more than three months, whereas IL-10 may remain elevated for up to 12 months. We suggest positive correlations between neutrophils, monocytes, eosinophils, and lymphocytes with different cytokines (IFN-γ, IL-6, IL-4, IL-17a, IL-2). Women were associated with lower hospitalisation rates and longer durations of Long Covid; increased lymphocyte counts were linked to hospitalisation due to COVID-19, while higher monocyte counts were associated with Long Covid durations of up to six months. We suggest that Long Covid patients may exhibit alterations in inflammatory markers, indicating a persistently pro-inflammatory microenvironment that tends to diminish after 12 months of Long Covid.

A New Laboratory Tool for COVID-19 Severity Prediction, CENIL Score.

Several studies investigated the risk factors for severe COVID-19-related outcomes. Early identification and proper treatment of COVID-19 patients who may develop severe pneumonia are crucial. The aim of this study was to detect the importance of the laboratory parameters for risk prediction of severe pneumonia in COVID-19 patients. This retrospective cohort study included COVID-19 patients' laboratory parameters at admission. Biochemical, hematological, coagulation, and inflammatory parameters values were compared between the non-severe and severe groups. A total of 534 COVID-19 patients were screened, and 472 of them were included in this study. The mean age of patients was 64 (±3.1) years; 242 (51.3%) were men. A total of 204 (43.2%) patients were diagnosed as severe cases. The independent predictors of severe illness were C-reactive peptide, Eosinophil, neutrophil-lymphocyte ratio, interleukin-6, and lactate dehydrogenase. These parameters were named as CENIL scores from 0 to 5 points. The findings of this study indicate that these biomarkers identified tend to increase progressively with disease severity in severe COVID-19 patients. Additionally, the CENIL risk score identified a specific cut-off value of 3, highlighting it as a critical threshold for identifying patients at high risk of severe COVID-19 progression. In this study, we identified biomarkers-including CRP, eosinophil count, NLR, IL-6, and LDH-named as CENIL risk score that can help predict the likelihood of severe disease at diagnosis. Clinicians may be more vigilant regarding the development of severe disease in patients with high CENIL risk scores, guided by clinical and radiological findings.

Management of multiple valve replacement operations for a young patient with hypereosinophilic syndrome and valvular heart disease: a case report

BackgroundHypereosinophilic syndrome (HES) is characterized by the overproduction of eosinophils and manifests as valvular disease and thrombogenesis. Herein, we report our experience with a patient with HES requiring multiple reoperations for prosthetic heart valve replacement via median sternotomy.Case presentationThe patient was a 54-year-old man who had undergone four valve replacement operations via median sternotomy (three mitral valve replacements and one double valve replacement) because of valvular diseases complicated by HES since he was 26 years old. All the artificial valves were bioprosthetic to prevent thrombotic events. At presentation, he had developed structural deterioration of the artificial aortic valve with severe stenosis. His prosthetic mitral valve did not fulfil the criteria for intervention, as it exhibited only mild regurgitation and no stenosis. The explanted mitral prosthetic valve at the previous (fourth) surgery had exhibited eosinophilic infiltration, resulting in the introduction of cyclosporin for poorly controlled HES. We conducted re-aortic valve replacement via a fifth median sternotomy using a bioprosthetic valve, and no eosinophilic infiltration was observed in the explanted valve. The patient was discharged on postoperative day 15 without complications.ConclusionsControlling eosinophil count during the pre- and postoperative course is vital in treating patients with HES after valve replacement surgery. A holistic management and therapeutic strategy, including prosthetic valve selection and medication for HES is required to improve outcomes of patients with HES and heart valve disease.

Meta-Analysis: Evaluating Placebo Rates Across Outcomes in Eosinophilic Oesophagitis Randomised Controlled Trials.

High placebo responses have limited drug development in eosinophilic oesophagitis. The optimal configuration of trial outcomes is uncertain. To inform more efficient future trial designs, to characterise clinical, endoscopic and histologic placebo responses in eosinophilic oesophagitis randomised controlled trials (RCTs). We updated a Cochrane systematic review and meta-analysis, searching multiple databases to January 1, 2024, to identify placebo-controlled RCTs evaluating medical therapies for patients with eosinophilic oesophagitis. The primary outcome was the pooled proportion of study-defined clinical, endoscopic and histologic responders and remitters randomised to placebo, using an intention-to-treat approach and random-effects model. Sources of heterogeneity were explored using meta-regression. We included 25 RCTs. The pooled proportion of clinical response was 41.0% [95% CI: 29.7%-52.8%] with substantial heterogeneity (I2 = 74.9%). On meta-regression, older age and a higher probability of being randomised to placebo reduced the likelihood of clinical response to placebo. The pooled proportion of histologic remission defined as a peak eosinophil count [PEC] ≤ 6 eosinophils per high power field [HPF] or ≤ 1 eosinophil/HPF was 4.3% [95% CI: 2.6%-6.2%] (I2 = 23.6%) and 1.3% [95% CI: 0.5%-2.5%] (I2 = 0%), respectively. The standardised mean difference in the Eosinophilic Oesophagitis Endoscopic Reference Score to placebo was -0.25 [95% CI: -0.41, -0.10]. Over 40% of patients in eosinophilic oesophagitis trials respond clinically to placebo, and this is associated with trial design factors such as randomisation ratio and trial population. Objective endoscopic and histologic measures are associated with very low placebo responses.

Peripheral Eosinophil Count May Be the Prognostic Factor for Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Treatment.

(1) Background: The importance of total eosinophil count in peripheral blood (EOS) as a type 2 inflammation marker is known to be fundamental in asthma, chronic sinusitis, and vasculitis. In cancer, despite their questionable antiproliferative effect, their role remains unclear. Our purpose was to describe the relationship between baseline blood EOS and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We retrospectively analyzed data from 137 adult patients who underwent surgical treatment for pancreatic ductal adenocarcinoma (PDAC) between the years 2012 and 2019. Patients with no recent history of systemic steroid use and without intraoperative metastases were included. Patients were categorized into two groups based on EOS (≥0.1 G/l and <0.1 G/l). Survival outcomes were analyzed using Cox proportional hazards regression models. (3) Results: According to EOS and PDAC stage, median OS values were as follows: in stage I-III, EOS ≥ 0.1 G/l group: 14.5 months, in stage I-III, EOS < 0.1 G/l group: 8.0 months, in stage IV, EOS ≥ 0.1 G/l group: 7.0 months, and in stage IV, EOS < 0.1 G/l group: 5.0 months. EOS < 0.1 G/l (vs. ≥0.1 G/l) was an independent prognostic factor for OS in both the uni- and multivariate Cox regression, respectively (HR = 1.48, p = 0.035 and HR = 1.57, p = 0.021). (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that type 2 inflammation may be the factor directly or indirectly lengthening the survival of patients with PDAC.

Abstract 4135360: Eosinophilic Myocarditis: An Atypical Presentation with a Labile Course: A Case Report

Case presentation: A 64-year-old man presented with one day of chest pain. Initial evaluation showed elevated cardiac enzymes (CE) and normal eosinophil count. Electrocardiogram (EKG) was unremarkable. Transthoracic echocardiogram (TTE) showed an ejection fraction (EF) of 40% and a moderate-large pericardial effusion with signs of tamponade. Pericardiocentesis was deferred due to the lack of a safe window. Left and right heart catheterization showed no occlusive disease or chamber pressure equalization. The patient developed worsening shock, raising suspicion for myocarditis and prompting an endomyocardial biopsy (EMB). He was placed on extracorporeal membrane oxygenation (ECMO) on day 3. The EMB resulted as eosinophilic myocarditis (EM), and high dose Methylprednisolone was started. He was decannulated from ECMO on day 10. Intra-operative transesophageal echocardiogram (TEE) post-decannulation showed a normal EF without segmental abnormalities. Three hours later, a rise in CEs was noted, and EKG showed ST elevations inferiorly. TTE showed a reduced EF with multiple segmental abnormalities concerning for myocardial infarction. A repeat coronary angiogram was unremarkable. Due to the residual pericardial effusion, the patient underwent a pericardial window draining 200 cc of serosanguinous fluid. Intra-operative TEE showed an EF of 20% with no improvement after drainage. He had a cardiac arrest during the procedure and was placed back on ECMO. High-dose steroids were resumed along with intravenous immunoglobulin. Despite interventions, the patient continued to deteriorate and he ultimately expired. Discussion: EM has high mortality and a variable course, often requiring EMB for diagnosis. As in our case, about 25% of cases present without peripheral eosinophilia. Pericardial effusion occurs in 34% of cases and tamponade in 6%. A distinct feature of this case is the decompensation associated with ST elevation and segmental abnormalities, thought initially to be myocardial infarction (MI), after an initial response to steroids. While the etiology of such decompensation is unclear, relapsing EM in the setting of tapering steroids is one explanation, as myocarditis and MI can share similar clinical features. Another explanation is cardiac tamponade, which has also been reported to mimic MI and myocarditis. Air embolism from ECMO decannulation is another possibility, though air embolisms may include cerebrovascular pathology, which was not observed.

Chronic Strongyloides stercoralis infection in Fijian migrants to the UK.

Introduction. Strongyloides stercoralis, the human threadworm, is a parasitic nematode with global distribution, estimated to infect over 600 million people. Chronic infection is often asymptomatic, but hyperinfection and dissemination syndromes can occur in the immunosuppressed with high case fatality rates. Whilst strongyloidiasis is endemic in Fiji, its prevalence in Fijian migrant groups in the UK is unknown.Gap Statement. No previous studies have been conducted on the prevalence of Strongyloides and other gastrointestinal parasites (GIPs) in Fijian migrants to the UK.Aim. We conducted a cross-sectional study of the prevalence of GIPs in a Fijian migrant population.Methodology. Participants completed a questionnaire on residence, travel and clinical symptoms and were asked to provide a serum sample for S. stercoralis IgG ELISA, venous blood samples for eosinophil count and a faecal sample for charcoal culture, multiplex real-time PCR (rtPCR) and microscopy after formalin-ethyl acetate concentration. Sequencing was performed on pooled Strongyloides larvae for nuclear 18S rRNA hyper-variable regions (HVRs) I and IV.Results. A total of 250 participants (94% male) with median (range) age 37 (20-51) years entered the study, 15 (1-24) years since leaving Fiji. S. stercoralis IgG ELISA was positive in 87/248 (35.1 %) and 14/74 (18.9 %) had a GIP detected in faeces. This included 7/74 (9.5 %) with Strongyloides and 5/74 (6.8 %) with hookworms. Dermatological symptoms were more common in those with Strongyloides, and eosinophilia (>0.5×109 cells per litre) was present in 55.6% of those with positive S. stercoralis IgG. rtPCR was the most sensitive faecal diagnostic test for Strongyloides and hookworms in faeces. Sequences of nuclear 18S rRNA for HVRs I and IV confirmed the presence of S. stercoralis.Conclusion. This first cross-sectional study in Fijian migrants found a high rate of chronic infection with GIPs, particularly S. stercoralis. Faecal microscopy was insensitive compared to charcoal culture, rtPCR or serology, demonstrating the importance of specialist parasitological tests when investigating people with a suspected chronic infection. Our study highlights an overlooked burden of strongyloidiasis in the UK and has implications for screening and treatment programmes in Fiji and for migrants from Fiji.