Eosinophil Count Research Articles

Dupilumab Efficacy and Safety in Children With Moderate-to-Severe Asthma and High Blood Eosinophils: A Post Hoc Analysis of VOYAGE

Elevated blood or tissue eosinophils are considered to characterize type 2 inflammation in children with asthma and are associated with increased exacerbation rates and worse asthma control. Dupilumab, a human monoclonal antibody that blocks type 2 inflammatory drivers IL-4 and IL-13, reduced severe exacerbation rates and improved lung function vs placebo in children aged 6-11 years with uncontrolled moderate-to-severe asthma in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). This post hoc analysis assessed dupilumab efficacy and safety in children from VOYAGE with moderate-to-severe asthma and ≥500 and <1500 blood eosinophils/μL at baseline. Children received add-on dupilumab (100/200 mg by body weight) or matched placebo every 2 weeks for 52 weeks. We assessed annualized severe exacerbation rates, least squares mean (LSM) change from baseline in pre-bronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1), and incidence of treatment-emergent adverse events. In children with elevated baseline eosinophils (N = 174), dupilumab vs placebo significantly reduced annualized exacerbation rates by 67% (95% CI: 38-82%; P < .001) and improved pre-bronchodilator ppFEV1 from baseline at Weeks 24 and 52 (LSM difference [95% CI] 7.58 percentage points [2.85-12.31]; P = .002; 7.98 percentage points [2.17-13.78]; P = .007, respectively). The incidence of treatment emergent adverse events was similar with dupilumab and placebo. Dupilumab significantly reduced severe exacerbations and improved lung function in children with moderate-to-severe asthma and baseline blood eosinophil counts ≥500 and <1500 cells/μL, with a safety profile comparable with the overall study population.

The impact of Charcot-Leyden Crystal protein on mesothelioma chemotherapy: targeting eosinophils for enhanced chemosensitivity

In mesothelioma (MPM), clinical evidence indicates that the absolute eosinophil count negatively correlates with overall survival and response to standard chemotherapy. Since eosinophils poorly infiltrate MPM tumours, we hypothesised that endocrine rather than paracrine pathways mediate the therapeutic response. We thus studied the effect of eosinophil-associated factors on response to chemotherapy in mesothelioma. The culture supernatant conditioned by primary human eosinophils was added to mesothelioma cells in presence of the standard chemotherapeutic regimen. The effectiveness of an anti-eosinophil treatment was evaluated in a preclinical model of C57BL/6 mice transplanted with mesothelioma tumour cells. Supernatant of eosinophils differentiated from EOL1 cells or directly isolated from peripheral blood inhibited apoptosis induced by cisplatin and pemetrexed in 2D cultures and in spheroids. Transcriptomic analysis indicated that the anti-apoptotic effect mediated by eosinophils involved molecular interactions with the Charcot-Leyden Crystal protein or Galectin-10 (CLC-P/Gal10). The functional relevance of CLC-P/Gal10 was demonstrated by antibody-mediated depletion. Recombinant human CLC-P/Gal10 mimicked the anti-apoptotic activity of eosinophil-derived supernatants. In the mouse model, eosinophilia did not significantly affect tumour growth but altered the response to chemotherapy. Finally, pretreatment of eosinophilia with the anti-Siglec-F antibody before chemotherapy restored the effectiveness of the treatment. This study provides a mechanistic rationale to clinical evidence correlating the poor outcome of patients with mesothelioma and with eosinophil-derived CLC-P/Gal10, opening new prospects for intervention in this fatal solid tumour. Belgian Foundation against Cancer, Fonds National de la Recherche Scientifique (FNRS), Télévie, Foundation Léon Fredericq, ULiège.

Immunomodulatory Potential of Melatonin in Immunosuppression: An in-vivo Study.

To assess the immunomodulatory effects of melatonin on the acquired immunity of immunosuppressed male Wistar rats by checking Interleukin 6 (IL-6) levels, total leucocyte counts (TLC), and differential leucocyte counts. Experimental study. Place and Duration of the Study: Animal laboratory, CMH Lahore Medical College, from June to October 2023. Fifty male Wistar rats, weighing 180g to 200g, were included in this study with 10 rats in each of the five groups namely cyclophosphamide (CP), CP + melatonin, CP + immunomodulator, melatonin-only, and control. A calculated dose of CP was administered intraperitoneally for 30 days (from 13/06/23 to 13/07/23) to each group except the control groups. After this, the experimental group was given melatonin CP + Melatonin for 7 days (from 14/07/23 to 20/07/23). CP + Immunomodulatory group was kept for comparison of immunomodulatory effects. Blood samples were drawn from all 5 groups. IL-6 was estimated through ELISA. Other parameters assessed were TLC and absolute differential leucocyte counts. Melatonin increased IL-6 levels significantly (p = 0.042) as well as the TLC levels (p <0.001) compared to the immuno-suppressed CP group. Melatonin was seen to have an upregulation of IL-6 levels in immunosuppression compared to the administration of immunomodulator preparation (p = 0.506) which was not as effective. Administration of melatonin significantly increased the TLC, neutrophil, lymphocyte, monocyte, and eosinophil count compared to known immunomodulators. Melatonin as a supplement may have some role in activating multiple immune response processes in immune-depressed states. It was also established that it allows quick recovery of cell components from immunosuppressed states. Melatonin, Immunomodulation, Rats, Interleukin-6, Acquired immunity, Cyclophosphamide.

Dupilumab Use in Patients With Hypereosinophilic Syndromes: A Multicenter Case Series and Review of the Literature

BackgroundHypereosinophilic syndromes (HES) are defined as hypereosinophilia with eosinophil-related clinical manifestations, some of which overlap in presentation with asthma, atopic dermatitis, eosinophilic esophagitis, and/or chronic rhinosinusitis with nasal polyps (CRSwNP). Dupilumab is approved to treat these conditions but can induce a transient rise in the absolute eosinophil count (AEC) and rare eosinophil-related complications. ObjectiveTo determine whether eosinophil-related complications of dupilumab are increased in HES. MethodsRetrospective chart review of patients with HES treated with dupilumab enrolled on an IRB-approved research protocol at the National Institutes of Health (NCT00001406) or receiving care at Walter Reed National Military Medical Center. Clinical response and treatment-emergent adverse events were recorded. Serum mediators were assessed in a subset of patients before and after dupilumab using stored samples. ResultsAmong the 28 patients (15 male, 13 female; median age 41.5), the most common prescribing indication for dupilumab was CRSwNP (n=11). Twenty-three patients (82%) showed significant clinical improvement on dupilumab. Hypereosinophilia (AEC >1.5x109/L) recurred or worsened in 9/20 patients on dupilumab monotherapy. Moreover, 4/20 (20%) patients developed an eosinophil-related complication with dupilumab discontinuation and/or addition of eosinophil-lowering therapy. None of the 8 patients who received dupilumab while in hematologic remission on an eosinophil-lowering biologic developed hypereosinophilia or an eosinophil-related complication. Serum IgE and eotaxin levels decreased on dupilumab therapy. ConclusionThese data suggest that dupilumab is effective in treating residual symptoms in HES patients but that the incidence of eosinophil-related complications is increased. Concomitant eosinophil-lowering therapy may reduce the risk of eosinophil-related complications during dupilumab therapy in patients with HES.

Diagnostic criteria for eosinophilic chronic rhinosinusitis: Comparative analysis and novel scoring system.

Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes. This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma etal.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field. Patients were randomly divided into estimation (n=430) and validation (n=210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval [CI], 0.670-0.835) in the estimation group, 0.729 (0.629-0.830) in the validation group, and 0.661 (0.584-0.738) in the 20-fold cross-validation with the entire dataset. We propose a novel scoring system that incorporates three key parameters: "novel score=blood eosinophil (%) + total Lund-Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present" greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention.

Biomarkers for house dust mite subcutaneous immunotherapy in allergic asthma

BackgroundAllergen immunotherapy (AIT) has demonstrated clinical efficacy in patients with allergic asthma. However, there is little information on biomarkers to evaluate the effect of house dust mite (HDM) subcutaneous immunotherapy (SCIT) on allergic asthma. ObjectiveTo evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SCIT. Methods139 patients with asthma sensitized to HDM were recruited, 75 subjects received SCIT as an add-on therapy to drug treatment, and 64 subjects received drug treatment alone. Spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total IgE (TIgE), serum specific IgE for HDM, and frequency of exacerbations (ACT scores) were measured at baseline, 6 months, and 12 months. The relationship between biomarkers and pulmonary function improvement was investigated. ResultsSCIT demonstrated a significant reduction in FeNO, serum IL-25 and ACT scores at 6 months and significantly improved airflow limitation at 12 months compared to pharmacotherapy. The changes in FEV1 were dramatically correlated with changes in blood eosinophils ( r =-0.35, P=0.002), FeNO ( r =-0.57, P＜0.0001), serum IL-25 ( r =-0.68, P＜0.0001) and ACT scores( r =0.562, P＜0.0001). The multivariate regression analysis revealed that the changes in serum IL-25 concentration and FeNO were independently associated with an increase in FEV1 (r2 = 0.514, P < 0.05, respectively) in patients with allergic asthma treated with HDM SCIT. ConclusionsAdding HDM SCIT to pharmacotherapy reduced serum IL-25 and FeNO and improved pulmonary function in allergic asthma. Serum IL-25 and FeNO may be useful biomarkers for predicting HDM SCIT in allergic asthma, even in the absence of significant improvement in airflow limitation.

Daily or twice daily treatment with topical steroids results in similar responses in eosinophilic esophagitis

Background and aimsFew data compare topical corticosteroid (tCS) dosing regimens and outcomes. We aimed to compare treatment outcomes in eosinophilic esophagitis (EoE) patients by once or twice daily dosing regimens. MethodsWe conducted a retrospective cohort study utilizing the UNC EoE Clinicopathologic Database of newly diagnosed EoE patients treated with a tCS who had a follow-up endoscopy with biopsy. Baseline data and outcomes were extracted. Bivariate and multivariate analyses compared patients at baseline and following initial tCS given as a once or twice daily dose. Results522 patients met inclusion criteria, 122 patients on once daily dosing (72% male; 91% white) and 400 patients on twice daily dosing (66% male; 89% white). Patients on twice daily dosing were older (28.8 ± 18.2 vs. 24.3 ± 18.0; p = 0.01) and reported more heartburn (40% vs. 25%; p = 0.004). On bivariate analysis, global symptomatic response (78% vs. 76%; p = 0.82), post-treatment eosinophil count (20.8 ± 27.2 vs. 25.6 ± 39.4; p = 0.21), post-treatment EREFS (2.2 ± 1.8 vs. 2.2 ± 2.0; p = 0.92), and histologic response (<15 eos/hpf; 56% vs 58%; p = 0.66) did not differ. Candida was less frequent with daily dosing (2% vs. 8%; p = 0.04). In multivariate analysis, the odds of histologic response did not differ by dose groups (aOR: 1.03; 95% CI: 0.67 – 1.60). ConclusionsEoE outcomes did not differ by daily or twice daily dosing regimens. These results inform tCS dosing regimens and reassure that both are effective.

Acupoint Autohemotherapy Alleviates Airway Inflammation in Asthmatic Rats via Upregulating Expression of Hemeoxygenase-1.

Acupoint autohemotherapy (AA), a therapeutic technique involving the subcutaneous injection of autologous blood into acupoints, has been empirically validated as safe and effective for treating asthma by alleviating symptoms and decreasing acute attacks, though its mechanism is not well understood. The role of heme oxygenase-1 (HO-1) in AA-induced suppression of asthmatic airway inflammation is examined. Twenty rats were assigned randomly to four groups, namely the Control, OVA, OVA + AA, and (OVA + Snpp) + AA. Rats in the OVA + AA and (OVA + Snpp) + AA received autologous blood injections into acupoints (BL13 and BL23) following OVA challenge. Rats in the (OVA + Snpp) + AA were concurrently subjected to intraperitoneal injections of Snpp, a inhibitor of HO-1. Airway inflammation was evaluated through HE staining, while the concentrations of cytokines in BALF were quantified using ELISA. The mRNA and protein levels of RORγt (Th17-specific transcription factor), Foxp3 (Treg-specific transcription factor), and HO-1 in lung tissue were assessed through qRT-PCR and WB. HE staining indicated that airway inflammation was alleviated in the OVA + AA. The OVA + AA displayed significantly lower counts of total cells and eosinophils in the BALF compared to both the OVA and (OVA + Snpp) + AA. The ELISA demonstrated a significant decrease in levels of pro-inflamatory cytokines (IL-4, IL-17A), and an increase in levels of anti-inflamatory cytokines (IFN-γ, IL-10), in the OVA + AA when compared to both OVA and (OVA + Snpp) + AA. The qRT-PCR and WB analyses revealed an upregulation of HO-1 and Foxp3 expression, and a downregulation of RORγt expression, in the OVA + AA when compared to OVA and (OVA + Snpp) + AA. The involvement of HO-1 in the underlying mechanism responsible for the anti-inflammatory effects of AA is evident.

Optimal Diagnostic and Treatment Response Threshold of the Eosinophilic Esophagitis Endoscopic Reference Score: A Single-Center Study of 102 Patients With Eosinophilic Esophagitis.

The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE. Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established. This study aims to establish these thresholds for the first time among Asian patients with EoE. Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 and November 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index. Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively (P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology were available for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold (sensitivity, 0.95; specificity, 0.88; Youden index, 0.83). The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3, respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

A Case Report of Isotretinoin: Acute Eosinophilic Pneumonia, A Rare Adverse Reaction

Abstract This is a case of acute eosinophilic pneumonia (AEP) in a 21-year-old woman with acne vulgaris who was treated with isotretinoin. During treatment, her blood tests showed normal results until the third month, when there was a slight increase in eosinophil count. In the fifth month of treatment, the patient presented to the pulmonology outpatient clinic with complaints of shortness of breath. Lung CT imaging revealed infiltration in both lungs characterized by ground glass opacities. AEP was diagnosed based on blood and imaging results. Isotretinoin therapy was terminated, and oral steroids were initiated, resulting in the improvement of the patient’s symptoms. The patient had no additional risk factors except for smoking, but she had not started or resumed smoking after quitting. This case report highlights the possibility of hypersensitivity pneumonitis following isotretinoin administration.

Acute Febrile Illness in India: An Epidemiological Retrospective Study.

Acute febrile illness (AFI) is a frequent occurrence in India, often complicated by a multitude of pathogenic and etiological factors. In this context, it is important to analyze the biochemical, hematological, and epidemiological clinical parameters of AFI patients in the North Indian population. This study included 1,819 patients of various ages who presented with new-onset acute febrile illness (AFI) between 2017 and 2021. Among these patients, 211, with a median age of 40 years (ranging from 2 to 85 years), were selected for further analysis. At enrollment, clinical examination involved collecting respiratory tract specimens, blood, and urine samples for bio-chemical analysis, with subsequent data analysis conducted using statistical methods. The following biochemical parameters were analyzed: C-reactive protein (CRP), alkaline phosphatase (ALP), serum glutamate-pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGT), and total protein serum. The hematological parameters included total leukocyte count (TLC), lymphocyte count, monocyte count, eosinophil count, red blood cell count (RBCs), packed cell volume (PCV), erythrocyte sedimentation rate (ESR), hematocrit value, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Additionally, clinical parameters such as phosphorus, urea, calcium, sodium, uric acid, bilirubin, and potassium were measured. Specific values observed were: SGPT (~113 IU/L in 2018), SGOT (~81 U/L in 2019), GGT (~148 g/L in 2018), and total protein serum (~7 g/L in 2020). The hematological parameters (TLC, lymphocyte, monocyte, RBCs, PCV, ESR, MCV, and MCH). The regression analysis was conducted to explore the temperature recorded at the time of admission, the duration of hospital stays, and biochemical as well as hematological variables of patients suffering from AFI. Karl-Pearson's correlation coefficient and variance inflation factor for each variable mentioned above. Biochemical and hematological parameters were analyzed over different years of intake in patients with Acute Febrile Illness (AFI). Further investigation is required to explore the mechanistic pathways of infection, and preventive measures will be implemented using natural products and other therapeutic interventions. Our data will offer the first systematic assessment of the etiological factors, along with regression analysis and the Karl-Pearson correlation coefficient for each variable in AFI patients.

Retrospective Evaluation of Clinical Characteristics of Children with Cat Sensitivity

Aims: Cat allergy has an important place among allergic diseases and it is known that environmental factors as well as genetic factors affect sensitisation. It has been reported that having a cat at home increases the risk of sensitisation, especially in susceptible individuals. The aim of this study was to retrospectively evaluate the clinical features of cat sensitisation in children. Methods: In this descriptive retrospective study, children aged 0-18 years with cat sensitisation who were admitted to the clinic between June 2023 and December 2023 were examined. Clinical characteristics, total IgE, eosinophil count, specific IgE values and skin prick test results were retrospectively evaluated using data obtained from the hospital database. Results: The study included 76 children with cat sensitisation. The mean age was 7 years and 56.6% were male. The most common diagnoses were asthma (63.2%) and allergic rhinitis (31.6%). Cat sensitisation was positive in 100% of the patients, house dust mite sensitisation was found in 78.9% and pollen sensitisation in 14.5%. Total IgE levels of patients with multiple allergies were significantly higher than those without multiple allergies. Conclusion: The study showed that additional allergen sensitisation was common in children with cat sensitisation and the most common diagnoses were allergic rhinitis and asthma. The findings are consistent with the existing literature and emphasise the importance of total IgE in the clinical management of allergic diseases.

High eosinophil counts aid in diagnosing Kawasaki disease in febrile children

Abstract Background Several recent studies have validated the newfound significance of elevated eosinophils in Kawasaki disease (KD). However, this finding was not incorporated into the suggested laboratory criteria outlined by the Kawasaki Disease Committee of the American Heart Association for assessing children with incomplete KD. Purpose We aimed to determine the potential benefits of including eosinophil levels in the laboratory evaluation of KD. Methods A retrospective cohort study involved 77,934 febrile children (FC, not KD) and 1,970 subjects diagnosed with KD. Participants were recruited from four hospitals, comprising two medical centers and two regional hospitals. The AHA recommends specific laboratory tests—white blood cell count, hemoglobin, platelet count, ALT levels, albumin, and urinalysis—for evaluating incomplete KD in children with a higher CRP than 30mg/dL. The first four items are standard blood assays. Additionally, we introduced high eosinophil counts as a new diagnostic criterion for identifying children with KD. Results All these five laboratory findings (anemia for age defined as below the 5th percentile), platelet count &amp;gt;450,000/mm3, white blood cell&amp;gt;15,000/mm3, ALT&amp;gt;40 U/L, and eosinophil count &amp;gt;190/mm3) are significantly different between KD children and FC. The proportion of having these features is higher in KD children than in FC (19.3% vs. 8.0% in anemia for age, 20.5% vs. 10.3% in thrombocytosis, 37.0% vs. 18.1% in leukocytosis, 45.7% vs. 5.8% in elevated ALT, and 62.6% vs. 29.3% in high eosinophils). Elevated eosinophil counts are most commonly associated with KD among these five parameters. Furthermore, when incorporating the parameter of elevated eosinophil counts, the proportion of KD children with at least two abnormalities rose from 35.4% to 60.7%. In a subgroup analysis of children with KD presenting at least two abnormalities, the proportion rose from 38.7% to 63.5% in the high CRP group (≧ 3.0 mg/L) and 21.6% to 49.0% in the low CRP group (&amp;lt; 3.0 mg/L), respectively. Conclusions Higher eosinophil counts are vital markers in KD children. This aids in the identification of additional potential KD cases, especially in those exhibiting low CRP levels.

Detection of chronic obstructive pulmonary disease and frequency of cardiopulmonary events in patients with a significant smoking history hospitalised for acute myocardial infarction

Abstract Background Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and also myocardial infarction (MI). Patients with COPD are more likely to have MI than those without and adequately treating COPD might improve cardiovascular outcomes. Reliable diagnosis is important for appropriate treatment. Prevalence of COPD in those hospitalised for MI has not been accurately established. Blood eosinophil count is an important guide to the benefit of inhaled corticosteroid (ICS) treatment in COPD. We aimed to accurately characterise lung function, symptom burden, eosinophil count and cardiopulmonary events in those with a significant smoking history hospitalised for acute MI. Methods Participants (n=216) with a smoking history of ≥10 pack-years currently hospitalised for acute MI were recruited at a single UK centre. Microspirometry and completion of the COPD Assessment Test (CAT) questionnaire were performed at enrolment. Presence and severity of COPD was graded using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. A high burden of COPD symptoms was defined as a CAT score of &amp;gt;10. Repeat CAT and assessment for relevant cardiopulmonary events was undertaken at 3 months and 1 year after enrolment. Results In the enrolled cohort, median age was 60 years (IQR 53-67), 26% were female, 57% were current smokers and median pack-year history was 32 (23-45). 41 of 216 (19 %, [95% CI 14-25]) had evidence of COPD, defined as FEV1/FEV6 &amp;lt;0.7 on best-attempt microspirometry, with 39 (95%) being GOLD2 or greater. Of the 41 with detected COPD, only 15 (37%, [22-53]) had a prior diagnosis. In those with evidence of COPD, a high burden of COPD symptoms was present in 63% of participants at enrolment, 40% at 3 months and 45% at 1 year. 20% [9-35] were receiving inhaled corticosteroids at enrolment. 63% [47-78] had eosinophil count ≥100 cells/mm3 and 17% [7-32] ≥300 cells/mm3. Among those with detected COPD, after 1 year 19.5% (95% CI 9-35%) had suffered a respiratory illness requiring prescription of medication, which was numerically but not statistically significantly higher than those without detected COPD (14.3% [10-20%]). In the COPD cohort, death, infection requiring hospitalisation, MI or unplanned coronary revascularisation, and bleeding requiring hospitalisation each occurred on two occasions (4.9%). Conclusions Based on these data, the prevalence of microspirometry-diagnosed COPD of any severity in patients with significant smoking history hospitalised for MI is around 19%. There is a high rate of undiagnosed and untreated disease, a significant burden of symptoms, including during convalescence, and around a 20% incidence of respiratory illness requiring medical treatment at 1 year. Gathering accurate data from this group is helpful in planning research and service improvement. Increasing detection of COPD in patients with MI would lead to improved cardiopulmonary outcomes.

Eosinophilic cationic protein and D-Dimer are potential biomarkers to predict response to antihistamines but not to omalizumab in chronic spontaneous urticaria

ABSTRACT Introduction: Biomarkers that could reliably anticipate the effectiveness of antihistamines and omalizumab in treating chronic spontaneous urticaria (CSU) have not been conclusively identified. Our objective was to examine how eosinophilic cationic protein (ECP), tryptase, D-dimer, and total Immunoglobulin E (IgE) impact the response to antihistamine and omalizumab treatments in individuals with CSU. Methods: In this cross-sectional retrospective study, CSU patients that had undergone treatment with either antihistamines or omalizumab for a minimum of 12 weeks between 2015 and 2021 at an Allergy and Immunology Department were analyzed. Several demographic and laboratory parameters including eosinophil counts, mean platelet volüme (MPV), sedimentation, C-reactive protein (CRP), antinuclear antibodies (ANA) and Anti-thyroperoxidase (Anti-TPO) and total IgE, tryptase, ECP and D-dimer were retrived from patient files. The association of these biomarkers with Urticaria Control Test (UCT) and the effect of these biomarkers on treatment response were evaluated. Treatment response was assessed using the UCT, with a score of UCT ≥ 12 indicating a responder and UCT < 12 indicating a non responder. Results: The patients in the omalizumab group were older, had a longer disease duration and had worse urticaria control (lower baseline UCT scores). 421 patients were treated with antihistamines and 88 patients were treated with omalizumab. ECP was found to be inversely correlated with baseline UCT (p < 0.001 r=−0.268). ECP and D-dimer levels of non-responder patients in the antihistamine group were significantly higher than in responder patients (ECP: 49 ng/mL vs 28.1 ng/mL, p < 0.001) (D-dimer: 0.60 mg/L vs 0.30 mg/L, p < 0.001), while there were no significant difference in terms of tryptase and total IgE. These four biomarkers were similar, in omalizumab responders and non responders. Conclusion: In this study with CSU, we looked at predictors of responses to treatments. ECP can serve as a marker of poor urticaria control and may predict antihistamine refractoriness along with D-dimer.

Clinical picture, outcomes and predictors of relapse in eosinophilia-associated coronary vasospasm: data from a European multicentric study

Abstract Background and aims Eosinophilia-associated coronary vasospasm is an under-recognized and scarcely reported life-threatening condition for whose management is undefined. Preliminary data suggest that eosinophil-targeted therapies could be beneficial. Our aim is to provide an in-depth report of the clinical picture, outcomes and predictors of relapse in patients with eosinophilia-associated coronary vasospasm. Methods European multicentric retrospective study, gathering twenty centers across France, Italy and Spain. Patients of 15 years or more with definite or suspected coronary vasospasm according to the 2017 International standardization of diagnostic criteria for vasospastic and concomitant (± 48 hours) eosinophilia (threshold: 0.5 x 109/L) were included in this study. Outcomes included vasospasm relapse and other major cardiovascular events (MACE) during follow-up. Predictors of relapse were assessed using bidirectional stepwise regression analysis. Results Thirty-seven patients (median age: 52 [42-64] years, 43% women) were included, among which 16 (43%) had aspirin-exacerbated respiratory disease, 16 (43%) and 13 (35%) fulfilled classification criteria for Eosinophilic Granulomatosis with Polyangiitis (all with negative antineutrophil cytoplasmic antibodies) and Hypereosinophilic syndrome, respectively. There was no predominant coronary territory involved. A iatrogenic trigger was evidenced in 7 (19%) patients, consisting in all cases but one of non-steroidal anti-inflammatory drugs. After a median follow-up of 32 [12-63] months, 20 (54%) patients relapsed (median time to first relapse: 10 [5−29] months), despite vasodilators regimen in 95% of cases. Besides coronary vasospasm(s), 13 (35%) patients experienced an additional MACE. In multivariate analysis, persistent eosinophilia (i.e. absolute eosinophil count &amp;gt; 0.5 x 109/L at the time of coronary vasospasm relapse or at last follow-up for relapsing and non-relapsing patients respectively) was the sole indepedendent predictor of relapse (Odds Ratio 8.87 [3.28-24.82]; p&amp;lt;0.001). All six patients treated with interleukin-5 biologics remained relapse-free under treatment. Conclusions Eosinophilia-associated coronary vasospasm can occur in patients with type 2 inflammation. Long-term normalization of absolute eosinophil counts appears crucial in preventing the recurrence of eosinophilia-associated coronary vasospasm, while conventional use of vasodilators seems ineficient.

Association Of Eosinophil And Total Ige Values With Allergy Test Results In Patients With Atopic Dermatitis

AOBJECTIVES: Atopic dermatitis (AD) is a chronic, recurrent, allergic inflammatory skin disease that may have a genetic predisposition. Eosinophilia is a common finding in patients with atopy. In our study, we aimed to investigate the relationship between eosinophil and IgE levels and allergy test results in patients with atopic dermatitis. METHODS: In this descriptive study, the files of patients diagnosed with atopic dermatitis and followed up in our Pediatric Allergy and Immunology Clinic between January 2021 and December 2022 were retrospectively reviewed. Age, gender, eosinophil, total IgE and specific IgE (for food and inhaled allergens) values were analyzed in the study. Skin prick test (SPT) was also performed in patients who had negative results for allergen-specific IgE. RESULTS: The absolute eosinophil count, eosinophil (%) and total IgE values of patients sensitized to at least one of the food and aeroallergens were significantly higher than those without allergen sensitization. The cut-off point of total IgE in predicting allergen sensitization was found to be 91.5 by ROC analysis. The sensitivity and specificity values for the cut-off point of total IgE were 73.3% and 72.9%. CONCLUSION: In this study, allergen sensitization was detected in 3 out of every 4 AD patients with total IgE and eosinophil values above the cut-off point we analyzed. Accordingly, we think that total IgE and eosinophil values are successful in predicting allergen sensitization. In clinics where specific IgE or SPT cannot be performed, eosinophil and total IgE values in whole blood will be useful for preliminary diagnosis.

Investigation of Blood Count-Based Inflammatory Biomarkers as Predictors of Response to Dupilumab Treatment in Patients with Chronic Rhinosinusitis with Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease often resistant to standard treatments. Dupilumab, a monoclonal antibody targeting the IL-4α receptor, has shown efficacy in CRSwNP, but a significant subset of patients do not respond to this therapy. This study aims to investigate pretreatment complete blood count (CBC)-based inflammatory biomarkers as predictors of response to dupilumab in patients with CRSwNP. This mono-centric, retrospective, single-arm longitudinal cohort study included 80 patients with uncontrolled CRSwNP who received dupilumab treatment at the Medical University of Graz. Patients were classified into responder and non-responder groups based on a reduction of >1 in nasal polyp score (NPS) and a sinonasal outcome test-22 (SNOT-22) score <40 points at six months. Pretreatment CBC-derived biomarkers, including eosinophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation indices including the aggregate inflammation systemic index (AISI), systemic inflammation index (SII), and systemic inflammation response index (SIRI), were analyzed for their predictive value. Of the 80 patients, 72.5% were classified as responders, while 27.5% were non-responders. A significant positive correlation was found between baseline eosinophil count and NPS reduction (p = 0.027), suggesting that higher eosinophil levels may predict higher NPS reduction in dupilumab treatment. However, no significant associations were observed between NLR, PLR, and systemic inflammation indices with treatment outcomes. Pretreatment eosinophil count may serve as a potential biomarker for predicting nasal polyp reduction in dupilumab treatment of CRSwNP. Other CBC-based inflammatory markers did not show significant predictive value. Further prospective studies are needed to validate these findings and explore additional, reliable biomarkers to optimize treatment outcomes for CRSwNP patients.

Hematological, cardiovascular and oxidative DNA damage markers associated with heavy metal exposure in electronic waste (e-waste) workers of Bangladesh

Electronic waste (e-waste) contains hazardous elements such as lead (Pb), cadmium (Cd), mercury (Hg), and other toxic elements that pose significant health risks to the population directly exposed. We recruited 199 e-waste recycling workers and 104 non-exposed workers in Bangladesh and analyzed heavy metals in blood and hair, as well as hematological and cardiovascular parameters including, blood lipids and blood pressure. We fitted quantile regression models at 0.5 quantile to evaluate the impact of blood Pb, Cd, and total hair Hg (THg) on hematological and cardiovascular parameters and the role of oxidative DNA damage (8-OHdG as a biomarker) in mediatin the relationship between exposures and outcomes. Exposed workers had elevated median blood Pb (11.89 vs. 3.63 µg/dL), moderate blood Cd (1.04 vs. 0.99 µg/L), and lower level of THg (0.38 vs. 0.57 ppm) in hair than non-exposed workers. Adjusted estimates showed that Pb was positively associated with red blood cell (RBC), eosinophil count, eosinophil percentage; and negatively associated with mean platelet volume (MPV), platelet large cell ratio (P-LCR) and platelet volume distribution width (PDW) (all p≤0.05). Cd was only associated with 0.57 units increase in red blood cell distribution width (RDW) percentage (95 % CI: 0.18, 0.95). In cardiovascular outcomes, Pb was associated with 1.42 units decrease in triglyceride, 1.58 units increase in low-density lipoprotein (LDL), 0.07 units increase in LDL/HDL and 0.49 units increase in systolic blood pressure (all p≤0.05). No associations were observed between THg and hematological or cardiovascular parameters. Urinary 8-OHdG concentrations were lower, and it did not mediate exposure-outcome relationships (all p≥0.05). Our data imply that e-waste exposure impairs hematological parameters, blood lipids, and blood pressure secondary to elevated Pb levels and poses a threat to exposed individuals. As such, continuous monitoring in longitudinal studies is warranted to assess the dose-response relationship and identify effective control measures.

Disease Overlap, Healthcare Resource Utilization, and Costs in Patients with Eosinophilic Granulomatosis with Polyangiitis: A REVEAL Sub-study.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an eosinophil-associated disease (EAD) characterized by inflammation in small- to medium-sized blood vessels. Inthe REal-world inVestigation of Eosinophilic-Associated disease overLap (REVEAL) study, overlap among 11 EADswas assessed. In the present sub-study, we evaluated EGPA overlapwith other EADs, all-cause EAD- and EGPA-related healthcare resource utilization (HCRU) and costs, and their relationship with blood eosinophil count and treatments received. REVEAL, a retrospective study, used Optum's de-identified Clinformatics® Data Mart Database. In this sub-study, eligibility criteria included an age of ≥ 12years, ≥ 1 EAD, continuous health-plan eligibility, and compliance with the EGPA/GPA case definition per International Classification of Diseases Ninth/Tenth Revision diagnosticcodes between 1 January 2015 and 30 June 2018. Patients were grouped based on whether they had received immunomodulators/cyclophosphamide/mepolizumab (ICM) or not (non-ICM). Of 701 patients with EGPA, 29.5% were in the ICM group. Overall, 72.2% had ≥ 1 overlapping EAD. The number of overlaps was similar for the ICM and non-ICM groups. In patients with blood eosinophil counts ≥ 300 cells/µL, 22.8% had ≥ 1 overlapping EAD. The mean annual all-cause cost was $98,644, 54.1% of which was from outpatients and 33.6% from inpatients. The mean annual EAD- and EGPA-related costs were $23,820 and $9,306, respectively. Patients in the non-ICM groupversus the ICM group had higher all-cause ($101,560 vs $91,684) but lower EAD-related ($22,733 vs $26,412) and EGPA-related ($6,171 vs $16,786) costs. All-cause HCRU and costs increased with increasing overlap. EGPA was associated with substantial HCRU and costs, driven by outpatient and inpatient settings. More overlapping EADs were associated with higher HCRU and costs, highlighting the need for treatment to reduce healthcare expenditure in these patients. Infographic available for this article.