Elevated Eosinophil Research Articles

Dissociation between physical capacity and daily physical activity in COPD patients. A population-based approach

BadkgroundPhysical capacity (PC) and daily physical activity (PA) are two crucial factors in the clinical course of COPD, although they do not always maintain a close relationship. The objectives were to evaluate the frequency of PC-PA dissociation in patients with COPD and subjects without airflow limitation (AL) and to identify its risk factors. MethodsA sample of 319 COPD patients and 399 subjects without AL was consecutively obtained from a population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, lung function testing, blood analysis and low-dose computed tomography (CT) scan with evaluation of lung density and airway wall thickness. A distance walked in 6 min > 70% predicted was considered an indicator of normal PC, while a Yale Physical Activity Survey summary index score <51 was used to identify with sedentary lifestyle. Results166 COPD patients (52.0%) reported a sedentary lifestyle with evidence of preserved PC, while this phenomenon was present in 188 (47.1%) subjects without AL. In the COPD group, symptoms of chronic bronchitis, depression and elevated hematocrit and blood eosinophil count were identified as independent risk factors for PC-PA dissociation. In turn, in the subjects without AL, the risk factors for PC-PA dissociation were low fat-free mass, obesity and anxiety, as well as reduced levels of HDL-cholesterol and the absence of osteoporosis. ConclusionsAlmost half of COPD patients and subjects without airflow limitation with preserved PC maintain a sedentary lifestyle, with different risk factors for sedentarism between both groups.

A Multi-Center Study of the Prevalence and Characteristics of Eosinophilic Phenotype and High IgE Levels Among Chinese Patients with Severe Asthma.

Patients with severe asthma have higher total- and asthma-related health burden than those whose disease is not severe. Recent medical advances in biologic therapies allow better control of asthma characterized by type 2 inflammation. To study the prevalence of eosinophilic phenotype and IgE levels in Chinese with severe asthma, and the relationship of these type 2 characteristics with asthma control, exacerbations and lung function. This was a multicenter cross-sectional observational study in Hong Kong, in Chinese adults with asthma on Step 4 or 5 of GINA treatment. Their blood eosinophil counts and total IgE levels were measured, and the relationship of these phenotypic parameters to the number of exacerbations in the past 12 months, and to symptom control in the past 4 weeks, were investigated. A total of 232 subjects were recruited from 6 centers. The mean age was 53.9±12.9 years, with 86 (37.1%) male, and the duration of diagnosed asthma was 26.2±15.7 years. A T-helper 2 (Th2) phenotype indicated by elevated eosinophils and/or IgE was present in 169 (72.8%) of patients. Of 232 patients, 43% had an eosinophilic phenotype (blood eosinophil count ≥300 cell/mm3), while 59% had high total IgE levels of >100 IU/mL (overlap with eosinophilic phenotype in 30%) and 44% had IgE levels of >150 IU/mL (overlap with eosinophilic phenotype in 22%). Subjects with eosinophilic phenotype and IgE >150 IU/mL had a higher rate (1.8 times) of uncontrolled asthma compared with those without such a combination. In Chinese adults with severe asthma defined by the use of conventional maintenance medication regimens, the prevalence of Th2 inflammation is comparable to that reported from other ethnic populations. Those with both eosinophil count ≥300 cell/mm3 and high IgE levels >150 IU/mL had a higher rate of uncontrolled asthma compared with those without a combination of these features.

The Effect of Montelukast in Children with Asthma Predictive Index Negative Episodic Viral Wheezing

Background: The effectiveness of montelukast for wheezing in young children is not clear. We aimed to evaluate whether the use of montelukast in the treatment of wheezing affects the number of attacks in children aged 1 to 6 years. Methods: This is a single center study. It was conducted between August 2019-2020. Children with aged 0-6 years old with a wheezing complaint who applied to the pediatric allergy and immunology outpatient clinic were included in the study. Modified asthma predictive index of the patients were evaluated. It was classified as Episodic Viral Wheezing (EVW) or Multiple Trigger Wheezing (MTW) based on the type of wheezing. Montelukast treatment was started and the number of attacks was checked during five months. Results: The total of 141 children who applied with wheezing complaints were included in the study. The majority of the patients were boys (n = 99). The mean age of the children was 4.2 ± 1.5 years. The median number of attacks before treatment was 2 (2-3). In 2.8% of the patients, eczema, in 12.8% of them, rhinitis and in 26.7% of them, elevated eosinophils were detected. IgE levels were 148.25 ± 279.20 IU/mL. According to the number of attacks before treatment, there was a significant decrease in the number of attacks in followup (p &lt; 0.001). Conclusion: In this study, montelukast has been shown to reduce the number of EVW attacks and we believe montelukast may be a potential treatment option for EVW in preschool children.

Respiratory morbidity in Schistosoma mansoni infection: a rapid review of literature.

Schistosomiasis contributes to 2.5 million disability-adjusted life years globally. Acute and chronic respiratory morbidity of Schistosoma mansoni (S. mansoni) is poorly documented in the literature. We conducted a rapid literature review of the burden of respiratory symptoms and lung function abnormalities among patients with S. mansoni. We also report the immunologic and lung imaging findings from the studies reviewed. We carried out a comprehensive literature search in Embase and MEDLINE from the inception of the databases to 13th March 2023. A total of 2243 patients with S. mansoni were reported from 24 case reports, 11 cross-sectional studies, 7 case series, 2 cohort studies and 2 randomized controlled trials. The prevalence of any respiratory symptom was 13.3-63.3% (total number of patients studied, n = 149). The prevalence of the individual symptoms among patients with S. mansoni in whom respiratory symptoms were sought for was as follows: cough (8.3-80.6%, n = 338), dyspnea (1.7-100.0%, n = 200), chest pain (9.0-57.1%, n = 86), sputum production (20.0-23.3%, n = 30) and wheezing (0.0 - 20.0%, n = 1396). The frequency of the symptoms tended to be higher in acute schistosomiasis. Restrictive lung disease was prevalent in 29.0% (9/31). The commonest chest imaging findings reported were nodules (20-90%, n = 103) and interstitial infiltrates (12.5-23.0%, n = 89). Peripheral blood eosinophilia was prevalent in 72.0-100.0% of patients (n = 130) with acute schistosomiasis and correlated with symptoms and imaging abnormalities. Three case reports in chronic S. mansoni reported elevated C-reactive protein, leucocyte, neutrophil and absolute eosinophil counts, eosinophil percentage, IgE and IgG4. There is a high prevalence of respiratory morbidity among patients with S. mansoni, particularly in the acute stage of the infection, although the studies are relatively small. Larger studies are needed to characterize respiratory morbidity in chronic schistosomiasis and determine the underlying clinical and immunological mechanisms.

IL-5-producing CD4+ Tcells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer.

Immune checkpoint blockade (ICB) has heralded a new era in cancer therapy. Research into the mechanisms underlying response to ICB has predominantly focused on Tcells; however, effective immune responses require tightly regulated crosstalk between innate and adaptive immune cells. Here, we combine unbiased analysis of blood and tumors from metastatic breast cancer patients treated with ICB with mechanistic studies in mouse models of breast cancer. We observe an increase in systemic and intratumoral eosinophils in patients and mice responding to ICB treatment. Mechanistically, ICB increased IL-5 production by CD4+ Tcells, stimulating elevated eosinophil production from the bone marrow, leading to systemic eosinophil expansion. Additional induction of IL-33 by ICB-cisplatin combination or recombinant IL-33 promotes intratumoral eosinophil infiltration and eosinophil-dependent CD8+ Tcell activation to enhance ICB response. This work demonstrates the critical role of eosinophils in ICB response and provides proof-of-principle for eosinophil engagement to enhance ICB efficacy.

Orthopedic implant hypersensitivity: Characterization of clinical presentation and effects of photobiomodulation therapy.

Orthopedic implants have improved the quality of life in aging society but also induces several kinds of tissue reactions, referred to as orthopedic implant hypersensitivity (OIH). The aim of our study is to report the clinical characteristics of OIH and the effects of photobiomodulation therapy (PBMT) on these groups of patients. We collected cases that complained of skin rashes with pruritus after orthopedic implants from January 2017 to June 2022 at the Dermatology clinic in Hualien Tzu Chi Hospital. We recorded the sites and material of orthopedic implants, skin lesions onset time, symptoms, location after implantation, and the disease duration. Laboratory tests were measured, including complete blood count, differential count, serum immunoglobulin E (IgE) level, as well as inflammatory and autoimmune markers. PBMT, including UVB311 nm or low-level laser therapy 808 nm, was performed. Dose, duration, and response were documented. Fourteen patients were diagnosed with OIH; twelve presented with localized eczema at the implant sites, and two with generalized eczema. Eleven patients (78.6%) had either elevated eosinophils percentage (>6%) or IgE level (>200 U/mL) or both. Seven patients (50%) had favorable outcome after PBMT and successfully withdrew from systemic steroid. In our case series, localized eczema at implant sites was a common cutaneous presentation in OIH. Hence, a surgical scar at the eczema site or long-term waxing and waning generalized eczema should prompt physicians on the possibility of OIH. Blood eosinophils percentage and serum IgE level can be reference biomarkers for OIH. PBMT provides a noninvasive and effective treatment strategy for immune regulation and tissue regeneration.

Cough, bloody sputum, eosinophil elevation and lung shadow

A 47-year-old man was referred to the pulmonary clinic with a 2-year history of productive cough and 3-month history of hemoptysis. Two years ago, his chest CT scan revealed a 2 cm×2 cm well-defined nodule in the right upper lung. His cough was alleviated without treatment. Three months ago, he had a productive cough with the bloody sputum after a running to catch the bus. Physical examination was normal. Complete blood count (CBC) showed an elevated eosinophil count (42.61%). Chest CT scan showed that the enlargement of the right upper lobe nodule (3.4 cm×3.3 cm), with bilateral pathy lesions distributed in the right upper lobe and the left lower lobe. Pathological study of needle specimen biopsy showed the lamellated cyst wall of hydatid cyst, brood capsule formation and hooklet. Pulmonary hydatidosis was diagnosed. It was recommended that the patient should be treated by surgery combined with albendazole. His symptoms relieved and lung nodules were shrinking without treatment after 5 years follow-up.

Churg Strauss syndrome with neuropathy: a case report

A 24 years old man with known history of asthma came with acute presentation of ascending weakness for4 days following flu like symptoms and worsening of asthma. His complete blood counts showed elevated eosinophil count. Nerve conduction showed neuropathy. Diagnosed Churg Strauss syndrome due to presence of asthma, eosinophilia, neuropathy and pulmonary infiltrates. Churg Strauss is systemic eosinophilic vasculitis involving multiple organ systems.

Evaluation Value of Allergy in Adenoid Hypertrophy Through Blood Inflammatory Cells and Total Immunoglobulin E.

Objective: Previous reports have indicated the close association of allergy with adenoid hypertrophy (AH). The aim of this study was to evaluate whether the inflammatory cells and total immunoglobulin E (IgE) in blood could be useful in the diagnosis of allergy in AH. Methods: Two hundred thirty-four children who underwent adenoidectomy were retrospectively enrolled in this study. Blood routine parameters were recorded, and total IgE as well as specific IgE (sIgE) of common allergens were tested perioperatively. The diagnostic utility of blood inflammatory cells and total IgE compared with serum sIgE testing was assessed. Results: In our study, 35.47% of AH children were atopic. Dermatophagoides farinae (d2), Dermatophagoides pteronyssinus (d1), and mold (mx2) were the most common sensitizing allergens. Significantly elevated eosinophil count, eosinophil to lymphocyte value, and total IgE were found in allergic AH children. As a result of receiver operating characteristic analysis, systemic total IgE could be a method to diagnose allergy in AH with a cutoff value of 46.55 and higher (area under curve [AUC] = 0.837; P < 0.001). Peripheral eosinophil count and eosinophil to lymphocyte were also able to predict positive allergy test result in AH children, with a cutoff value of 0.295 (AUC = 0.721; P < 0.001) and 0.082 (AUC = 0.685; P < 0.001), respectively. Conclusion: The presence of allergy can be distinguished by looking at peripheral total IgE and/or blood eosinophils in AH, which will guide us to the precise treatment of AH and also reduce the cost considerably.

Do General Pathologists Assess Gastric and Duodenal Eosinophilia?

Eosinophilic diseases of the gastrointestinal tract (EGIDs), eosinophilic gastritis (EoG), and eosinophilic duodenitis (EoD) are rarely suspected clinically and infrequently detected by pathologists. To determine whether histories of allergic or eosinophilic disorders and requests to rule out EoG and EoD affect pathologists' awareness of eosinophils in gastrointestinal biopsies. Thirty-one community-based pathologists were given 16 sets of biopsies from gastric and duodenal mucosa with elevated eosinophils, Helicobacter pylori gastritis, atrophic gastritis, normal stomach and duodenum, lymphocytosis, and celiac disease. Participants were assigned to 3 groups: group A did not receive histories of allergic or eosinophilic conditions; group B received similar histories plus a clue of possible allergic or eosinophilic conditions; and group C received the same histories as B and was asked to rule out EoG/EoD. A list of gastric and duodenal diagnoses and a space for comments were provided. Results were analyzed descriptively. Pathologists correctly diagnosed most noneosinophilic gastrointestinal disorders, indicating competence in gastrointestinal pathology. With respect to EoG and EoD, pathologists in group C performed significantly better that those in groups A and B. The combined odds ratio with 95% CI was 12.34 (2.87-53.04), P < .001, for A versus C and 4.02 (1.60-10.09), P < .02, for B versus C. Most pathologists neither reported gastric/duodenal eosinophilia nor diagnosed EoG/EoD, even when provided histories of eosinophilic disorders. Requests to rule out EoG/EoD resulted in only 4 of 11 participants evaluating and counting eosinophils in some cases. Simple evidence-based histopathologic criteria are needed before pathologists can be expected to consider and diagnose EGIDs.

Single Center Experience with Off-Label Benralizumab in Refractory Hypereosinophilic Syndrome Demonstrates a Satisfactory Safety and Efficacy Profile

Background: Hypereosinophilic syndrome (HES) is characterized by blood and/or tissue eosinophilia resulting in end-organ damage. HES can be primary clonal (in which the eosinophil is part of clonal hematopoiesis), secondary (due to eosinophilic stimulating cytokines) or idiopathic (I-HES). A careful diagnostic work-up for primary causes, as well as vigilant surveillance for end-organ damage should be performed to establish an underlying and treatable diagnosis. Regardless of the cause, treatment of symptomatic HES is mandatory. Treatment may consist of steroids, tyrosine kinase inhibitors, hydroxycarbamide, or interferon, with variable responses. Long-term use of steroids leads to osteoporosis and infections, and treatment with steroid sparing drugs might be hampered by other side-effects. More aggressive treatments such as alemtuzumab is efficacious but severely immunosuppressive. Several antibodies targeting IL-5 or its receptor have been successfully applied for eosinophilic asthma but only mepolizumab is registered by the FDA and EMA for HES. Benralizumab, an anti-IL5R antibody, was efficacious and safe for treatment of HES in a phase-I/II trial. A randomized phase-III trial comparing benralizumab with placebo is currently recruiting. We have treated 15 patients with off-label benralizumab for severe refractory HES or HES with unacceptable steroid dependency. Methods: 15 adults (8 with I-HES, 6 with secondary (lymphocytic variant) HES and one patient with HES secondary to sarcoidosis; age range 19-69 years; 10 male, 5 female) from our institution were treated with benralizumab at a monthly dose of 30 mg after giving consent for off-label use. All had absent HES translocations by FISH, and no evident underlying diagnosis was present after extensive diagnostics including bone marrow examination with cytogenetics and molecular diagnostics. They all were refractory or had contra-indications to conventional treatment, or steroids could not be reduced to an acceptable dose. All had elevated eosinophil counts at diagnosis above 0.6 x 109/L (range 0.32-90 x109/L, median 8.3 x 109/L) except one patient who had a level of 0.32 while on 30 mg prednisolone per day. All patients had at least one organ affected by HES, including 2 patients with myocarditis. Three patients had previously received mepolizumab in a HES dose, 2 of whom were refractory and consequently stopped while one had an allergic reaction necessitating cessation. Median follow-up time after starting benralizumab was 22 months (range, 1-34 months). Results: In terms of efficacy, 13 patients had a reduction of their eosinophil count to below 0.05 x 109/L after one dose, one patient had a reduction from 8.13 to 0.72 x 109/L, with a count that is still decreasing while stopping all other medication. Eosinophil count decreased from 12.38 to 1.45 x 109/L in another patient, but benralizumab was stopped due to the development of MDS, which was most likely the cause of the eosinophilia despite normal cytogenetics and molecular diagnostics at time of diagnosis. All but 2 patients were off steroids completely after 4 months. All but 2 patients experienced a clinically relevant improvement of organ function, mostly to complete resolution of objective symptoms or signs. Interestingly, the 2 patients who did not experience clinically significant reduction of symptoms, despite reduction of peripheral eosinophil counts, both had colitis as one of the cardinal disease symptoms. In one, the diagnosis was revised to inflammatory bowel disease with secondary eosinophilia. In terms of safety, 2 patients experienced mild headache for a few days after the benralizumab dose, and 1 patient had a mild malar rash after the first dose. One patient stopped due to the development of MDS necessitating other treatment and one stopped due to refractoriness. Interestingly, this patient subsequently had an excellent response on mepolizumab, on both clinical symptoms as well as reduction of eosinophil counts. All patients with objective clinical benefit remain on treatment. Conclusions: We report on the largest single center cohort of patients treated with off-label benralizumab for HES. The use of this drug has proven a safe and effective treatment for HES regardless of the underlying cause. It reduces eosinophil counts, reverses organ-damage and use of steroids in most patients. Side effects are infrequent and mild and no severe adverse events were observed.

Emergence of Chronic Myeloid Leukemia in Patients with Myeloproliferative Neoplasms: A Single-Institution Experience

Introduction: Chronic myeloid leukemia (CML) is characterized by the presence of the BCR-ABL1 translocation and is typically distinct from other myeloproliferative neoplasms (MPN) including polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). Concurrent diagnosis of CML and MF is uncommon and infrequently described in case reports.1 Moreover, very few cases have been described of CML occurring after an established diagnosis of MPN.2-3 Due to the rarity of concurrent CML and MPN, management strategies in this population are not defined. In addition, the latency time from the emergence of BCR-ABL1 positive clones to a clinical diagnosis of CML in this setting is largely unknown. To address these questions, we interrogated our institutional experience and retrospectively analyzed available specimens. Methods: We collected information on patients seen at Massachusetts General Hospital (MGH) from January 1 2012 to January 1 2022 for CML occurring after an established diagnosis of MPN. Available stored samples were retrospectively tested for BCR-ABL1 with a fusion transcript assay (MGH Center for Integrated Diagnostics, Boston, MA). Results: We identified four patients with CML preceded by MPN (Table 1). Three patients had prior MF, diagnosed 4.3-7.6 years before the onset of CML; two of these had post-ET MF. Patient #4 had ET diagnosed 4 years prior to onset of CML, then went on to develop MF 4.9 years after CML diagnosis. None of the patients were on JAK inhibitors, hydroxyurea or interferon at the time of CML diagnosis. All patients had a leukocytosis with characteristic features on the differential prompting evaluation for CML. The median white blood cell count was 45.83 x 10^9/L (range 27.49-121.02). All four patients had an elevated basophil count (median 2.99 x 10^9/L, range 1.1-22.99) and two had an elevated eosinophil count (median 1.11 x 10^9/L, range 0.55-44.17). Regarding MPN driver mutations, one patient had a JAK2 V617F, one patient had a CALR exon 9 deletion, and two patients had no identifiable mutations on extended next-generation sequencing. For CML treatment, three patients received dasatinib (two with 100 mg daily, one with 50 mg daily), whereas one received nilotinib (150 mg twice daily). Two achieved a major molecular response (MMR) (at 7 and 8 months); one had an early molecular response at 6 months (last follow-up); one (with e13-a3 transcript) could not be quantified on a standard PCR assay but achieved a complete cytogenetic response by 4 months. At the time of last follow-up, two patients were in MMR on tyrosine kinase inhibitors (TKI), whereas two underwent allogeneic hematopoietic cell transplantation (alloHCT), primarily for progression of MF. We retrospectively interrogated available samples for evidence of the BCR-ABL1 translocation prior to a clinical diagnosis of CML. Patient #2 was followed at MGH for MF and thus had available samples. We identified BCR-ABL1 transcripts in the peripheral blood three months prior to his clinical diagnosis of CML (unable to be quantified due to e13-a3 transcript); there were no available samples from earlier in his disease course for testing (Figure 1). Discussion: CML can emerge in patients with MPN. Herein, we describe four cases of this phenomenon. Signs of CML evolution included marked leukocytosis, as well as basophilia and eosinophilia. Despite underlying MF, three patients tolerated full-dose TKI and achieved molecular responses early in their disease course. However, MPN progression remained a significant challenge, with two patients ultimately requiring an alloHCT. Of note, we found evidence of BCR-ABL1 in the peripheral blood three months prior to clinically apparent CML in one patient. Experiments using single cell techniques in patients with concurrent MPN and CML would provide insights into the clonal architecture and are in planning stages.

Development of sensitization to peanut and storage proteins and relation to markers of airway and systemic inflammation: A 24-year follow-up.

Long-time data of peanut allergy over time is sparse. We aimed to study the longitudinal development of sensitization to peanut extract and storage protein allergen molecules and associations with asthma status, airway and systemic inflammation markers. The Swedish birth cohort BAMSE followed 4089 participants with questionnaires, clinical investigations and blood sampling between 0 and 24 years. Information on (i) background factors at 2months, (ii) peanut allergy symptoms and IgE data (ImmunoCAP) at 4, 8, 16, and 24 years, and (iii) IgE to storage proteins, lung function data including exhaled nitric oxide (FENO) as well as systemic inflammatory markers at 24 years of age were collected. The prevalence of peanut extract sensitization, defined as IgE ≥ 0.35 kUA /L, was 5.4%, 8.0%, 7.5%, and 6.2% at 4, 8, 16, and 24 years of age, respectively. Between 8 and 24 years of age, (33/1565) participants developed IgE-ab to peanut extract (median 1,4, range 0.7-2.6kUA /L), and among those 85% were also sensitized to birch. Only six individuals developed sensitization to Ara h 2 (≥0.1kUA /L) between 8 and 24 years of age, of whom three had an IgE-ab level between 0.1-0.12 kUA /L. Storage protein sensitization was associated with elevated FENO, blood eosinophils and type 2 inflammation-related systemic proteins. Sensitization to peanut extract after 4 years of age is mainly induced by birch cross-sensitization and IgE to Ara h 2 rarely emerges after eight years of age. Storage protein sensitization is associated with respiratory and systemic inflammation.

Subgroups in the treatment of nasal polyposis with dupilumab: A retrospective study.

Dupilumab has been shown to be safe and effective in treating chronic rhinosinusitis with polyposis (CRSwNP). There is to this date no published data whether subgroups like patients with aspirin exacerbated respiratory disease (AERD), increased histologic eosinophilia or elevated blood eosinophil or IgE-levels benefit greater from dupilumab therapy. Moreover, there is no data comparing the efficacy of functional endoscopic sinus surgery (FESS) with dupilumab therapy. We conducted a retrospective chart review of all patients that were treated at a tertiary referral center for CRswNP with dupilumab. We also contacted the patients with a questionnaire to evaluate the efficacy of previous surgeries and dupilumab therapy by visual analogue scale (VAS) and the glasgow benefit inventory (GBI) as well as report on side effects. Overall, 75 patients were included in the study at hand that reported back 138 times. While dupilumab treatment was efficient, we found no systematic evidence of greater efficacy of dupilumab in patients with AERD, histologic eosinophilia or increased blood eosinophil or IgE-levels. All patients showed a considerable decrease in subjective burden of disease, objective smell tests and endoscopic findings. From the patients point of view, dupilumab therapy showed greater efficacy both in the VAS and the GBI overall and all subcategories but "social support." Dupilumab is efficient in treating CRSwNP; this effect is independent from disease characteristics like AERD, histologic eosinophilia, serum IgE-levels or eosinophil counts. There seems to be a group of patients that benefit greater from dupilumab therapy compared to FESS.

Patient Characteristics Associated With Reactions to Mrgprx2-Activating Drugs in an Electronic Health Record–Linked Biobank

Mas-related G protein-couple receptor x2 (Mrgprx2) activation underlies many common non-IgE-mediated adverse drug reactions (ADRs), yet the features of patients with reactions to Mrgprx2-activating drugs are unknown. To characterize the patient-specific comorbidities and laboratory characteristics associated with listed reactions to Mrgprx2-activating drugs, including fluoroquinolones, morphine, neuromuscular blockade agents, vancomycin, and leuprolide. We used a retrospective, observational cohort study design using electronic health record data from adults with an Mrgprx2-activating drug exposure recorded within a hospital system clinical Biobank. Odds ratios (ORs) and incidence rate ratios for clinical characteristics associated with ADRs, including immediate hypersensitivity reactions, were calculated using multivariable logistic regression. Among 59,763 patients exposed to Mrgprx2-activating drugs, 4846 had a listed ADR. Female sex, White race, asthma (OR: 1.81, 95% confidence interval [CI]: 1.68-1.94), chronic urticaria (OR: 1.73, 95% CI: 1.46-2.05), and mastocytosis (OR: 12.79, 95% CI: 5.98-27.02) were associated with increased odds of a reaction. Overall, patients with allergic disease had 1.21 times the rate of an ADR compared with patients without allergic disease. Elevated absolute eosinophil count was inversely associated with reactions, and there was no association with elevated total IgE. Observed associations were similar in a patient subgroup with immediate-type hypersensitivity reactions. Specific allergic diseases and common allergic biomarkers are differentially associated with ADRs to Mrgprx2-activating drugs. These findings from a large, "real world" drug-exposed population highlight clinical factors that may contribute to non-IgE-mediated drug allergy.

Re: Elevated Peripheral Blood Eosinophils during Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Prevalence and clinical significance.

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Rethinking blood eosinophil counts: Epidemiology, associated chronic diseases, and increased risks of cardiovascular disease.

The distribution and determinants of blood eosinophil counts in the general population are unclear. Furthermore, whether elevated blood eosinophil counts increase risk for cardiovascular disease (CVD) and other chronic diseases, other than atopic conditions, remains uncertain. We sought to describe the distribution of eosinophil counts in the general population and determine the association of eosinophil count with prevalent chronic disease and incident CVD. A population-based adult cohort was followed from January 1, 2006, to December 31, 2020. Electronic health record data regarding demographic characteristics, prevalent clinical characteristics, and incident CVD were extracted. Associations between blood eosinophil counts and demographic characteristics, chronic diseases, laboratory values, and risks of incident CVD were assessed using chi-square test, ANOVA, and Cox proportional hazards regression. Blood eosinophil counts increased with age, body mass index, and reported smoking and tobacco use. The prevalence of chronic obstructive pulmonary disease, hypertension, cardiac arrhythmias, hyperlipidemia, diabetes mellitus, chronic kidney disease, and cancer increased as eosinophil counts increased. Eosinophil counts were significantly associated with coronary heart disease (hazard ratio [HR], 1.44; 95% CI, 1.12-1.84) and heart failure (HR, 1.62; 95% CI, 1.30-2.01) in fully adjusted models and with stroke/transient ischemic attack (HR, 1.37; 95% CI, 1.16-1.61) and CVD death (HR, 1.49; 95% CI, 1.10-2.00) in a model adjusting for age, sex, race, and ethnicity. Blood eosinophil counts differ by demographic and clinical characteristics as well as by prevalent chronic disease. Moreover, elevated eosinophil counts are associated with risk of CVD. Further prospective investigations are needed to determine the utility of eosinophil counts as a biomarker for CVD risk.

TREATMENT OF HYPEREOSINOPHILIA WITH MEPOLIZUMAB IN A 6-YEAR-OLD BOY

<h3>Introduction</h3> Hypereosinophilic syndrome (HES) is a rare cause of hypereosinophilia among pediatric patients. Mepolizumab, an IL-5 antagonist, is an effective treatment for hypereosinophilia approved for patients ≥12 years of age, but for younger children treatment remains limited to corticosteroids or other cytoreductive agents. This case illustrates successful treatment of hypereosinophilia with mepolizumab in a child. <h3>Case Description</h3> A previously heathy 6-year-old male presented with three days of fatigue, fever, and right cervical lymphadenopathy with an elevated absolute eosinophil count (AEC) that peaked at 83,350 cells/microliter. Work up for infectious disease, end-organ damage, and malignancy with flow cytometry and cytogenetics from blood, bone marrow and lymph node biopsy were negative. Mepolizumab 100 mg injected subcutaneously was given, leading to progressive decline in AEC to 3,370 cells/microliter after 14 days. Fevers, fatigue, and lymphadenopathy resolved. Monthly mepolizumab and close monitoring is planned. <h3>Discussion</h3> HES is a heterogenous group of disorders; of paramount concern is development of malignancy and end-organ damage due to eosinophilic infiltration of tissues. Although effective for hypereosinophilia, long-term treatment with corticosteroids is associated with significant adverse events and may cause diagnostic uncertainty when monitoring pre-malignant conditions. While mepolizumab is approved for children ≥6 years of age for the treatment of asthma, it is not approved for HES in this age group. This case highlights that mepolizumab is an effective steroid-sparing therapy in young children with hypereosinophilia that allows continued monitoring for malignancy without masking or delaying diagnosis from corticosteroid use.

CASE OF CHRONIC EOSINOPHILIC PNEUMONIA IN A PREGNANT PATIENT

<h3>Introduction</h3> Chronic eosinophilic pneumonia (CEP) is an idiopathic pulmonary disease with abnormal eosinophil accumulation within the lung. Diagnostic criteria include prolonged respiratory symptoms (such as cough, dyspnea and wheezing), eosinophilia within the lungs/blood and abnormal chest imaging, without evidence of other etiologies of eosinophilic pneumonia. <h3>Case Description</h3> A 26 year-old female was diagnosed with CEP at 23 years of age after presenting with worsening symptoms of severe persistent asthma. Bronchoalveolar lavage fluid showed elevated eosinophil count and imaging showed pulmonary ground glass opacities. The patient was treated with oral corticosteroids, inhaled corticosteroids, montelukast and fexofenadine. She was a candidate for mepolizumab, but had become pregnant; therefore, biologic therapy was held. During the beginning of her pregnancy, peak flow was 457 l/min. Her oral steroid therapy was initially weaned; however, the dosing was increased towards the end of pregnancy due to worsening symptoms. Peak flow by the third trimester of pregnancy was 300 l/min. Her pregnancy was complicated by placental abruption; she received steroid stress dosing prior to C-section delivery. There were no reported postoperative complications to the patient or her child. Her peak flow had increased to 500 l/min one month after delivery. She began biologic therapy with mepolizumab 9 months after delivery, along with steroid tapering, with good response. <h3>Discussion</h3> While CEP is an increasingly studied entity, pregnancy in the setting of a known CEP diagnosis is not well documented. Management of such patients is challenging in view of their uncontrolled obstructive airways symptoms and systemic steroid requirement.

Harnessing artificial intelligence to infer novel spatial biomarkers for the diagnosis of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory condition of the esophagus associated with elevated esophageal eosinophils. Second only to gastroesophageal reflux disease, EoE is one of the leading causes of chronic refractory dysphagia in adults and children. EoE is a clinicopathologic disorder and the histological portion of the diagnosis requires enumerating the density of esophageal eosinophils in esophageal biopsies, and evaluating additional features such as basal zone hyperplasia is helpful. However, this task requires time-consuming, somewhat subjective manual analysis, thus reducing the ability to process the complex tissue structure and infer its relationship with the patient's clinical status. Previous artificial intelligence (AI) approaches that aimed to improve histology-based diagnosis focused on recapitulating identification and quantification of the area of maximal eosinophil density, the gold standard manual metric for determining EoE disease activity. However, this metric does not account for the distribution of eosinophils or other histological features, over the whole slide image. Here, we developed an artificial intelligence platform that infers local and spatial biomarkers based on semantic segmentation of intact eosinophils and basal zone distributions. Besides the maximal density of eosinophils [referred to as Peak Eosinophil Count (PEC)] and a maximal basal zone fraction, we identify the value of two additional metrics that reflect the distribution of eosinophils and basal zone fractions. This approach enables a decision support system that predicts EoE activity and potentially classifies the histological severity of EoE patients. We utilized a cohort that includes 1,066 biopsy slides from 400 subjects to validate the system's performance and achieved a histological severity classification accuracy of 86.70%, sensitivity of 84.50%, and specificity of 90.09%. Our approach highlights the importance of systematically analyzing the distribution of biopsy features over the entire slide and paves the way toward a personalized decision support system that will assist not only in counting cells but can also potentially improve diagnosis and provide treatment prediction.