Immune Response Dynamics and Biomarkers in COVID-19 Patients.

BACKGROUND: The immune response dynamics in COVID-19 patients remain a subject of intense investigation due to their implications for disease severity and treatment outcomes. We examined changes in leukocyte levels, eosinophil activity, and cytokine profiles in patients hospitalized with COVID-19. METHODS: Serum samples were collected within the first 10 days of hospitalization/confirmed infection and analyzed for eosinophil granule proteins (EGP) and cytokines. Information from medical records including comorbidities, clinical symptoms, medications, and complete blood counts were collected at the time of admission, during hospitalization and at follow up approximately 3 months later. RESULTS: Serum levels of eotaxin, type 1 and type 2 cytokines, and alarmin cytokines were elevated in COVID-19 patients, highlighting the heightened immune response (p < 0.05). However, COVID-19 patients exhibited lower levels of eosinophils and eosinophil degranulation products compared to hospitalized controls (p < 0.05). Leukocyte counts increased consistently from admission to follow-up, indicative of recovery. CONCLUSION: Attenuated eosinophil activity alongside elevated chemokine and cytokine levels during active infection, highlights the complex interplay of immune mediators in the pathogenesis COVID-19 and underscores the need for further investigation into immune biomarkers and treatment strategies.

Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

Single-cell RNA-sequencing of human eosinophils in allergic inflammation in the esophagus.

BACKGROUND: Eosinophils are elusive cells involved in allergic inflammation. Single-cell RNA-sequencing (scRNA-seq) is an emerging approach to deeply characterize cellular properties, heterogeneity, and functionality. OBJECTIVES: We sought to comprehensively characterize the transcriptome and biological functions of human eosinophils at a site of severe allergic inflammation in the esophagus (ie, eosinophilic esophagitis [EoE]). METHODS: We employed a gravity-based scRNA-seq methodology to sequence blood eosinophils from patients with EoE and control individuals compared to a reanalyzed public scRNA-seq dataset of human esophageal eosinophils of EoE patients. We used flow cytometry, immunostaining, and a stimulation assay to verify mRNA findings. RESULTS: In total, scRNA-seq was obtained from 586 eosinophils (188 from blood [n = 6 individuals] and 398 from esophagus [n = 6 individuals]). The esophageal eosinophils were composed of a population of activated eosinophils (enriched in 659 genes compared with peripheral blood-associated eosinophils) and a small population of eosinophils resembling peripheral blood eosinophils (enriched in 62 genes compared with esophageal eosinophils). Esophageal eosinophils expressed genes involved in sensing and responding to diverse stimuli, most notably IFN-γ, IL-10, histamine and leukotrienes, and succinate. Esophageal eosinophils were most distinguished from other esophageal populations by gene expression of the receptors CCR3, HRH4, SUCNR1, and VSTM1; transcription factors CEBPE, OLIG1, and OLIG2; protease PRSS33; and the hallmark eosinophil gene CLC. A web of bidirectional eosinophil interactions with other esophageal populations was derived. Comparing esophageal eosinophils and mast cells revealed that esophageal eosinophils expressed genes involved in DNAX-activation protein-12 (also known as TYROBP) interactions, IgG receptor-triggered events, immunoregulation, and IL-10 signaling. CONCLUSIONS: In EoE, esophageal eosinophils exist as 2 populations, a minority population resembling blood eosinophils and the other population characterized by high de novo transcription of diverse sensing receptors and inflammatory mediators readying them to potentially intersect with diverse cell types.

Controlled human exposures to diesel exhaust or particle-depleted diesel exhaust with allergen modulates transcriptomic responses in the lung.

The evidence associating traffic-related air pollution (TRAP) with allergic asthma is growing, but the underlying mechanisms for this association remain unclear. The airway epithelium is the primary tissue exposed to TRAP, hence understanding its interactions with TRAP and allergen is important. Diesel exhaust (DE), a paradigm of TRAP, consists of particulate matter (PM) and gases. Modern diesel engines often have catalytic diesel particulate filters to reduce PM output, but these may increase gaseous concentrations, and their benefits on human health cannot be assumed. We conducted a randomized, double-blinded, crossover study using our unique in vivo human exposure system to investigate the effects of DE and allergen co-exposure, with or without particle depletion as a proxy for catalytic diesel particulate filters, on the airway epithelial transcriptome. Participants were exposed for 2 h before an allergen inhalation challenge, with each receiving filtered air and saline (FA-S), filtered air and allergen (FA-A), DE and allergen (DE-A), or particle-depleted DE and allergen (PDDE-A), over four different occasions, each separated by a 4-week washout period. Endobronchial brushings were collected 48 h after each exposure, and total RNA was sequenced. Differentially expressed genes (DEGs) were identified using DESeq2, followed by GO enrichment and pathway analysis. FA-A, DE-A, and PDDE-A exposures significantly modulated genes relative to FA-S, with 462 unique DEGs identified. FA-A uniquely modulated the highest number (↑178, ↓155), followed by DE-A (↑44, ↓23), and then PDDE-A exposure (↑15, ↓2); 6 DEGs (↑4, ↓2) were modulated by all three conditions. Exposure to PDDE-A resulted in modulation of 285 DEGs compared to DE-A exposure, further revealing 26 biological process GO terms, including "cellular response to chemokine" and "inflammatory response". The transcriptional epithelial response to diesel exhaust and allergen co-exposure is enriched in inflammatory mediators, the pattern of which is altered upon particle depletion.

Increased Allergic Inflammation and Decreased Lung Insulin Sensitivity in Offspring of Obese Allergic Mothers.

Epidemiological studies demonstrate that maternal obesity and maternal allergy are major risk factors for asthma in offspring. However, the impact of maternal allergy and obesity on offspring lung insulin signaling and allergen responsiveness is not known. To evaluate this, allergic and non-allergic female mice were fed a high fat diet or low-fat diet from 7 weeks before pregnancy until weaning. Neonatal pups were allergen-sensitized and allergen-challenged and then were assessed for obesity, insulin signaling, and allergic inflammation. Compared to pups of non-obese non-allergic mothers, allergen-challenged pups of obese non-allergic mothers, non-obese allergic mothers and obese allergic mothers had bronchoalveolar lavage eosinophilia, with the pups of obese allergic mothers having the highest bronchoalveolar lavage eosinophilia. These pups also had lower insulin-induced lung AKT-phosphorylation, indicating a decrease in lung parenchymal insulin sensitivity. In cross-fostering experiments, allergen-challenged pups exposed to both pre- and post-natal obese allergic mothers had the highest level of BAL eosinophilia. Maternal obesity or allergy increased offspring serum allergen-specific IgE and IL-5 that was highest when the mother was both obese and allergic. Also, allergen-challenged pups exposed to both pre- and post-natal obese allergic mothers had the highest level of IL5. In summary, offspring born to obese allergic mothers have decreased lung insulin sensitivity and have increased lung allergic inflammation. Interestingly, our data also demonstrates that there is both a pregnancy and post-pregnancy aspect of maternal allergy and obesity that enhance allergen responsiveness in offspring.

Eosinophils in Colorectal Cancer: Emerging Insights into Anti-Tumoral Mechanisms and Clinical Implications.

Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes.

Receptor for Advanced Glycation End Product (RAGE) Modulates Inflammation During Feeding of the Hard Tick, Haemaphysalis longicornis in Mice.

Ticks are notorious blood-sucking ectoparasites that affect both humans and animals. They serve as a unique vector of various deadly diseases. Here, we have shown the roles of the receptor for advanced glycation end products (RAGE) during repeated infestations by the tick Haemaphysalis longicornis using RAGE-/- mice. In primary infestation, a large blood pool developed, which was flooded with numerous RBCs, especially during the rapid feeding phase of the tick both in wild-type (wt) and RAGE-/- mice. Very few inflammatory cells were detected around the zones of haemorrhage in the primary infestations. However, the number of inflammatory cells gradually increased in the subsequent tick infestations, and during the third infestations, the number of inflammatory cells reached to the highest level (350.3 ± 16.8 cells/focus). The site of attachment was totally occupied by the inflammatory cells in wt mice, whereas very few cells were detected at the ticks' biting sites in RAGE-/- mice. RAGE was highly expressed during the third infestation in wt mice. In the third infestation, infiltration of CD44+ lymphocytes, eosinophils and expression of S100A8 and S100B significantly increased at the biting sites of ticks in wt, but not in RAGE-/- mice. In addition, peripheral eosinophil counts significantly increased in wt but not in RAGE-/- mice. Taken together, our study revealed that RAGE-mediated inflammation and eosinophils played crucial roles in the tick-induced inflammatory reactions.

Eosinophil-derived extracellular vesicles: isolation and classification techniques and implications for disease pathophysiology.

Eosinophils are leukocytes characterized by their ability to release granule content that is highly rich in enzymes and proteins. Besides the anti-helminthic, bactericidal, and antiviral properties of eosinophils and their secretory granules, these also play a prominent role in the pathophysiology of diseases like asthma, eosinophilic esophagitis, and other hypereosinophilic conditions by causing tissue damage and airway hyperresponsiveness. Although this cell was first recognized mainly for its capacity to release granule content, nowadays other capabilities such as cytokine secretion have been linked to its physiology, and research has found that eosinophils are not only involved in innate immunity, but also as orchestrators of immune responses. Nearly 10 years ago, eosinophil-derived extracellular vesicles (EVs) were first described; since then, the EV field has grown exponentially, revealing their vital roles in intracellular communication. In this review, we synthesize current knowledge on eosinophil-derived EVs, beginning with a description of what they are and what makes them important regulators of disease, followed by an account of the methodologies used to isolate and characterize EVs. We also summarize current understanding of eosinophil-derived vesicles functionality, especially in asthma, the disease in which eosinophil-derived EVs have been most widely studied, describing how they modulate the role of eosinophils themselves (through autocrine signaling) and the way they affect airway structural cells and airway remodeling. Deeper understanding of this cell type could lead to novel research in eosinophil biology, its role in other diseases, and possible use of eosinophil-derived EVs as therapeutic targets.

Eosinophils and chronic obstructive pulmonary diseases (COPD) in hospitalized COVID-19 patients.

BACKGROUND: The emergence of coronavirus disease 2019 (COVID-19) as a global health emergency necessitates continued investigation of the disease progression. This study investigated the relationship between eosinophilia and the severity of COVID-19 in chronic obstructive pulmonary disease (COPD) patients. METHODS: This cross-sectional study was conducted on 73 COPD patients infected by COVID-19 in Afzalipour Hospital, Iran. Peripheral blood samples were collected for hematological parameter testing, including eosinophil percentage, using Giemsa staining. Eosinophilia was defined as≥ 2% and non-eosinophilia as< 2%. The severity of pulmonary involvement was determined based on chest CT severity score (CT-SS) (based on the degree of involvement of the lung lobes, 0%: 0 points, 1-25%: 1 point, 26-50%: 2 points, 51-75%: 3 points, and 76-100%: 4 points). The CT-SS was the sum of the scores of the five lobes (range 0-20). RESULTS: The average age of patients was 67.90±13.71 years, and most were male (54.8%). Non-eosinophilic COPD patients were associated with more severe COVID-19 (P= 0.01) and lower oxygen saturation (P= 0.001). In addition, the study revealed a significant difference in the chest CT severity score (CT-SS) between non-eosinophilic (9.76±0.7) and eosinophilic COPD patients (6.26±0.63) (P< 0.001). Although non-eosinophilic COPD patients had a higher mortality rate, this difference was not statistically significant (P= 0.16). CONCLUSIONS: Our study demonstrated that reduced peripheral blood eosinophil levels in COPD patients with COVID-19 correlate with unfavorable outcomes. Understanding this association can help us identify high-risk COPD patients and take appropriate management strategies to improve their prognosis.

Asthma in patients with the syndrome of undifferentiated dysplasia of connective tissue: peculiarities of the course or mutually aggravating mechanisms?

OBJECTIVE: Aim: To analyse laboratory and biochemical features of the severe persistent course of asthma in patients with undifferentiated connective tissue dysplasia (UCTD) syndrome, and their phenotypic and visceral stigmas of dysembryogenesis. PATIENTS AND METHODS: Materials and Methods: We enrolled 60 male patients with asthma, aged from 23 to 62 years (mean age (46.83 ±0.85) years): 30 patients with the background of UCTD, and 30 - without UCTD. We analysed clinical, somatometric, surveying (original questionnaire based on the phenotypic map of Glesby), instrumental (spirography, echocardiography, endoscopy, esophagofibrogastroduodenoscopy) and laboratory (including eosinophilic granulocytes and aldosterone levels) data. RESULTS: Results: Correlations were found in men with UCTD between the number of UCTD markers and rate of earlobe diagonal fold (r=+0.75; р<0.05), asthenic constitution (r=+0.72; р<0.05), easy bruising (r=+0.7; p<0.05) and straight abdominal line hernia (r=+0.52; p<0.05). Average aldosterone serum level in patients with UCTD (176,10 ±11,22) was significantly higher than in those without UCTD (142,77 ±9,43), (p<0.05), as well as average eosinophils levels (1.3 ±0.25 vs. 0.57 ±0.12, p<0.05). In the absolute majority of patients with UCTD (93.3%) asthma onset was confirmed after pneumonia, and their age of asthma manifestation was significantly higher (37.2 ±1.21) than in patients without UCTD (21.4 ±1.13). Also, in patients with UCTD there was a high number of severe exacerbations during the last year (2.7 ±0.12 per year) on the background of high doses of combined inhaled glucocorticosteroids use. CONCLUSION: Conclusions: Identified "phenotypic profile", clinical and biochemical features of patients with asthma on the background of UCTD syndrome, which determine the severe course and early formation of asthma complications, will further accelerate the diagnosis of this asthma phenotype and improve approaches to the selection of treatment regimens for these patients.

Helminth infection induces a distinct subset of CD101hi lung tissue-infiltrating eosinophils that are differentially regulated by type 2 cytokines.

Eosinophils play divergent roles in health and disease, contributing to both immunoregulatory and proinflammatory responses. Helminth infection is strongly associated with eosinophilia and the induction of the type 2 cytokines interleukin (IL)-5, IL-4 and IL-13. This study aimed to elucidate the heterogeneity of pulmonary eosinophils in response to helminth infection and the roles of IL-5, IL-4 and IL-13 in driving pulmonary eosinophil responses. Using the murine helminth model Nippostrongylus brasiliensis (Nb), we characterize a subtype of eosinophils, defined by high expression of CD101, that is induced in the lungs of Nb-infected mice and are phenotypically distinct from lung eosinophils that express low levels of CD101. Strikingly, we show that the two eosinophil subtypes have distinct anatomical localization within the lung: CD101low eosinophils are predominantly localized in the lung vasculature, whereas Nb-induced CD101hi eosinophils are predominantly localized in the extravascular lung niche. We show that CD101hi eosinophils are also induced across other models of pulmonary infection and inflammation, including a nonlung-migrating helminth infection, house dust mite-induced allergic inflammation and influenza infection. Furthermore, we demonstrate that the induction of CD101hi tissue eosinophils is independent of IL-5 and IL-4 signaling, but is dependent on intact IL-13 signaling. These results suggest that IL-13 produced during helminth infection and other disease states promotes a pulmonary tissue-infiltrating program in eosinophils defined by high expression of CD101.

Chronic Spontaneous Urticaria: Etiology and Pathogenesis.

Urticaria, also known as hives, is a common condition thought to affect up to 20% of individuals worldwide in their lifetime. This skin condition is characterized by the appearance of pruritic, erythematous papules or plaques with superficial swelling of the dermis. The major complaint is the symptom of pruritus. Angioedema, which involves a deeper swelling of dermal or mucosal tissues, may accompany urticaria. Urticaria can be classified by both time course of symptoms and the underlying etiology.

Spontaneous Lethal Outbreak of Influenza A Virus Infection in Vaccinated Sows on Two Farms Suggesting the Occurrence of Vaccine-Associated Enhanced Respiratory Disease with Eosinophilic Lung Pathology.

Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of infiltrating eosinophils. The purpose of this study was to characterize these lung lesions with special emphasis on the phenotypes of inflammatory cells, the presence of eosinophilic peroxidase (EPO), and neutrophil extracellular traps (NETs). The number of Sirius red-stained eosinophils was significantly higher in the lungs of IAV-infected sows compared to healthy pigs, indicating a migration of eosinophils from blood vessels into the lung tissue stimulated by IAV infection. The detection of intra- and extracellular EPO in the lungs suggests its contribution to pulmonary damage. The presence of CD3+ T lymphocytes, CD20+ B lymphocytes, and Iba-1+ macrophages indicates the involvement of cell-mediated immune responses in disease progression. Furthermore, high numbers of myeloperoxidase-positive cells were detected. However, DNA-histone-1 complexes were reduced in IAV-infected sows, leading to the hypothesis that NETs are not formed in the IAV-infected sows. In conclusion, our findings in the lungs of IAV-infected vaccinated sows suggest the presence of so far unreported field cases of vaccine-associated enhanced respiratory disease.

Eosinophils Play a Surprising Leading Role in Recurrent Urticaria in Horses.

Urticaria, independent of or associated with allergies, is commonly seen in horses and often shows a high reoccurrence rate. Managing these horses is discouraging, and efficient treatment options are lacking. Due to an incidental finding in a study on horses affected by insect bite hypersensitivity using the eosinophil-targeting eIL-5-CuMV-TT vaccine, we observed the prevention of reoccurring seasonal urticaria in four subsequent years with re-vaccination. In an exploratory case series of horses affected with non-seasonal urticaria, we aimed to investigate the role of eosinophils in urticaria. Skin punch biopsies for histology and qPCR of eosinophil associated genes were performed. Further, two severe, non-seasonal, recurrent urticaria-affected horses were vaccinated using eIL-5-CuMV-TT, and urticaria flare-up was followed up with re-vaccination for several years. Eotaxin-2, eotaxin-3, IL-5, CCR5, and CXCL10 showed high sensitivity and specificity for urticarial lesions, while eosinophils were present in 50% of histological tissue sections. The eIL-5-CuMV-TT vaccine reduced eosinophil counts in blood, cleared clinical signs of urticaria, and even prevented new episodes of urticaria in horses with non-seasonal recurrent urticaria. This indicates that eosinophils play a leading role in urticaria in horses, and targeting eosinophils offers an attractive new treatment option, replacing the use of corticosteroids.

Correlation of Eosinophils and Type 2 Inflammatory Mediators with Osteitis in Chronic Rhinosinusitis with Nasal Polyps.

Objective: Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP. Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated. Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P<0.001), periosteal proteins (P<0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P<0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively. Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.

Eosinophil-Epithelial Cell Interactions in Asthma.

BACKGROUND: Eosinophils have numerous roles in type 2 inflammation depending on their activation states in the blood and airway or after encounter with inflammatory mediators. Airway epithelial cells have a sentinel role in the lung and, by instructing eosinophils, likely have a foundational role in asthma pathogenesis. SUMMARY: In this review, we discuss various topics related to eosinophil-epithelial cell interactions in asthma, including the influence of eosinophils and eosinophil products, e.g., granule proteins, on epithelial cell function, expression, secretion, and plasticity; the effects of epithelial released factors, including oxylipins, cytokines, and other mediators on eosinophils, e.g., on their activation, expression, and survival; possible mechanisms of eosinophil-epithelial cell adhesion; and the role of intra-epithelial eosinophils in asthma. KEY MESSAGES: We suggest that eosinophils and their products can have both injurious and beneficial effects on airway epithelial cells in asthma and that there are bidirectional interactions and signaling between eosinophils and airway epithelial cells in asthma.

scRNA-seq profiling of human granulocytes reveals expansion of developmentally flexible neutrophil precursors with mixed neutrophil and eosinophil properties in asthma.

Neutrophils and eosinophils share common hematopoietic precursors and usually diverge into distinct lineages with unique markers before being released from their hematopoietic site, which is the bone marrow (BM). However, previous studies identified an immature Ly6g(+) Il-5Rα(+) neutrophil population in mouse BM, expressing both neutrophil and eosinophil markers suggesting hematopoietic flexibility. Moreover, others have reported neutrophil populations expressing eosinophil-specific cell surface markers in tissues and altered disease states, confusing the field regarding eosinophil origins, function, and classification. Despite these reports, it is still unclear whether hematopoietic flexibility exists in human granulocytes. To answer this, we utilized single-cell RNA sequencing (scRNA-seq) and CITE-seq to profile human BM and circulating neutrophils and eosinophils at different stages of differentiation and determine whether neutrophil plasticity plays role in asthmatic inflammation. We show that immature metamyelocyte neutrophils in humans expand during severe asthmatic inflammation and express both neutrophil and eosinophil markers. We also show an increase in tri-lobed eosinophils with mixed neutrophil and eosinophil markers in allergic asthma and that IL-5 promotes differentiation of immature blood neutrophils into tri-lobed eosinophilic phenotypes suggesting a mechanism of emergency granulopoiesis to promote myeloid inflammatory or remodeling response in patients with chronic asthma. By providing insights into unexpectedly flexible granulocyte biology and demonstrating emergency hematopoiesis in asthma, our results highlight the importance of granulocyte plasticity in eosinophil development and allergic diseases.

Blood eosinophils levels in a Colombian cohort of biomass-and tobacco-related COPD patients.

Introduction: Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death among adults. In 2019, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy incorporated blood eosinophils as a biomarker to identify patients at increased risk of exacerbations which, with the history of exacerbations during the previous year, allows identification of patients who would benefit from anti-inflammatory treatment to reduce the risk of future exacerbations. The aim of this study was to describe demographic and clinical characteristics, eosinophil counts, and exacerbations in a cohort of COPD patients stratified by clinical phenotypes (non-exacerbator, frequent exacerbator, asthma-COPD overlap) in a Colombian cohort at 2600 meters above sea level. Methods: A descriptive analysis of a historical cohort of patients with a confirmed diagnosis of moderate to severe COPD (FEV1/FVC < 0.7 and at least one risk factor for COPD) from two specialized centers with comprehensive disease management programs was performed from January 2015 to March 2019. Data were extracted from medical records 1 year before and after the index date. Results: 200 patients were included (GOLD B: 156, GOLD E: 44; 2023 GOLD classification); mean age was 77.9 (SD 7.9) years; 48% were women, and 52% had biomass exposure as a COPD risk factor. The mean FEV1/FVC was 53.4% (SD 9.8), with an FEV1 of 52.7% (20.7). No differences were observed between clinical phenotypes in terms of airflow limitation. The geometric mean of absolute blood eosinophils was 197.58 (SD 2.09) cells/µL (range 0 to 3,020). Mean blood eosinophil count was higher in patients with smoking history and frequent exacerbators. At least one moderate and one severe exacerbation occurred in the previous year in 44 and 8% of patients, respectively; during the follow-up year 152 exacerbations were registered, 122 (80%) moderate and 30 (20%) severe. The highest rate of exacerbations in the follow-up year occurred in the subgroup of patients with the frequent exacerbator phenotype and eosinophils ≥300 cells/µL. Discussion: In this cohort, the frequency of biomass exposure as a risk factor is considerable. High blood eosinophil count was related to smoking, and to the frequent exacerbator phenotype.

Associations between eosinophils and cancer risk in the UK Biobank.

Eosinophils exhibit anti-tumor cytotoxic responses in the tumor microenvironment and may contribute to tumor immunosurveillance. To assess the relationship between circulating eosinophils and cancer risk, we analyzed data from 443,542 adults aged 38-73 in the UK Biobank, who were initially cancer-free, had over a year of follow-up, and baseline white blood cell count measurements. Using multivariable Cox regression, we estimated hazard ratios (aHR) and 95% confidence intervals (95%CI) for each quartile increase in absolute eosinophil count (AEC) across 58 cancer types, adjusting for relevant confounders. During a median follow-up of 5.8 years, 22,747 incident cancer cases were diagnosed. We observed an inverse association, which met Bonferroni significance, between AEC and overall cancer risk (aHR, 95%CI 0.97, 0.95-0.98). Notably, 16 cancer types showed borderline associations (p <.05) with AEC, with 12 types displaying an inverse relationship. These included four hematologic cancers (acute and other myeloid leukemia, other lymphocytic leukemia, and chronic lymphocytic leukemia/small lymphocytic lymphoma; aHR range; 0.58-0.87) and eight nonhematologic cancers (melanoma and nose/middle ear, soft tissue/heart, gum/other mouth, tongue, lung, colon, and breast cancers; aHR range: 0.65-0.95). Higher AEC showed a borderline significant association with increased risk for intrahepatic bile duct cancer, Hodgkin lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukemia (aHR range: 1.13-1.42). Our study, the largest to date, provides insights into the relationship between blood eosinophils and a comprehensive list of incident cancers. The inverse association between AEC and overall cancer risk suggests a protective role for eosinophils in tumor surveillance.