Number Of Eosinophils In Blood Research Articles

Long-term mepolizumab treatment reduces relapse rates in super-responders with eosinophilic granulomatosis with polyangiitis

BackgroundThe mainstay of treatment for eosinophilic granulomatosis with polyangiitis (EGPA) is systemic corticosteroid therapy; some patients also receive intravenous immunoglobulins, other immunosuppressive agents, and biologics. Mepolizumab, an anti-interleukin-5 monoclonal antibody, induces remission and decreases the daily corticosteroid dose; however, the clinical efficacy of mepolizumab in EGPA and the prognosis with long-term treatment with this drug are unknown.MethodsSeventy-one EGPA patients were treated at Hiratsuka City Hospital, Japan, between April 2018 and March 2022. We administered mepolizumab for a mean of 2.8 ± 1.7 years to 43 patients in whom remission could not be induced by conventional treatment. After excluding 18 patients who had received mepolizumab for less than 3 years, we classified 15 patients into a “super-responder group” (the daily dose of corticosteroids or other immunosuppressant could be decreased, or the interval between IVIG treatments could be prolonged) and 10 patients into a “responder group” (neither of these changes was achievable). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and other immunosuppressants, Birmingham Vasculitis Activity Score (BVAS), and relapse frequency before and after mepolizumab initiation were determined.ResultsBlood eosinophil count at diagnosis and the lowest serum IgG level before mepolizumab treatment were significantly higher in super-responders than in responders (p < 0.05). In super-responders, the prednisolone dose at last visit on mepolizumab treatment was lower than that before treatment (p < 0.01) and lower than that at last visit in the responders (p < 0.01). In both groups, peripheral blood eosinophil numbers and BVAS were lower after starting mepolizumab than before (p < 0.01). BVAS before mepolizumab (p < 0.05) and at last visit (p < 0.01) were lower in super-responders than in responders. Relapse rates every year after the start of mepolizumab were lower in super-responders than in responder groups (p < 0.01). In super-responders, relapse rates were lower during the 3 years following mepolizumab initiation (p < 0.01) and at last visit (p < 0.01) were significantly lower than after 1 year of treatment.ConclusionMepolizumab treatment of super-responders sustainably reduced the relapse rate.

Eosinopenia as a Prognostic Biomarker for Noninvasive Ventilation Use in COPD Exacerbations.

In recent years, blood eosinophils have been evaluated as a surrogate biomarker for eosinophilic airway inflammation and as a prognostic indicator of the outcomes of hospitalized COPD subjects. During an exacerbation of COPD, eosinopenia has been proposed as a prognostic marker of adverse outcomes. The aim of the present post hoc analysis was to elucidate the effectiveness of blood eosinophils for predicting the need of NIV in subjects with COPD exacerbation. Consecutive subjects admitted to a hospital for COPD exacerbation were included in the analysis. The eosinophil count from the first complete blood count was used to designate the eosinophil groups. The relationship between the clinical characteristics and blood eosinophil counts, as dichotomized using 150 cells/μL, was evaluated. Results Subjects with blood eosinophil number < 150 k/μL had a more severe disease on admission compared to subjects with ≥150 k/μL, regarding pH 7.400 (7.36, 7.44) vs. 7.42 (7.38, 7.45), p = 0.008, PO2/FiO2 levels 238.1 (189.8, 278.6) vs. 276.2 (238.2, 305.6), p < 0.001, CRP (mg/L) levels 7.3 (3.1, 19.9) vs. 3.5 (0.7, 7.8), p < 0.001 and required a longer hospital stay (days) 10.0 (8.0, 14.0) vs. 5.0 (3.0, 7.0) p < 0.001 respectively. The number of blood eosinophils correlated with the levels of CRP upon admission (p < 0.001, r = -0.334), with arterial pH upon admission (p < 0.030, r = 0.121), with PO2/FiO2 (p < 0.001, r = -0.248), and with duration of hospital stay (p < 0.001, r = -0.589). In the multinomial logistic regression analysis, blood eosinophil count < 150 k/μL was an independent predictor of the use of NIV during hospital stay. During COPD exacerbation, low blood eosinophil levels upon admission are related to more severe disease and can be used as a predictor of the need of NIV. Further prospective studies are needed to identify the use of blood eosinophil levels as a predictor of unfavorable outcomes.

Efficacy of two-year anti-IgE therapy in patients with severe allergic bronchial asthma in Sverdlovsk region

Introduction. The study of omalizumab efficacy in patients with severe bronchial asthma (SA) in randomized clinical trials is limited to 52 weeks. In real clinical practice, patients can receive the drug for much longer.Aim. Evaluate the one-year and two-year efficacy of omalizumab in patients with SA in Sverdlovsk region.Material and methods. The study included patients (n = 54) with allergic and mixed SA from the registry of Sverdlovsk region. Omalizumab efficacy was assessed over 12 and 24 months of therapy by dynamics of asthma exacerbations frequency, the use of health care resources, the need for short-acting beta-agonists (SABA) and systemic glucocorticosteroids (SGCS), the level of asthma control according to ACT, and the quality of life according to AQLQ, FEV1 levels and peripheral blood eosinophils.Results. During 12 months of omalizumab therapy, the reduction in asthma exacerbation rate was 63.7% (from 2.01 ± 1.51 per patient per year to 0.73 ± 1.03) (p &lt; 0.001), which was accompanied by a decrease in emergency calls and hospitalizations rates by 92.4 and 84.1%, respectively (p &lt; 0.001). Improved asthma control (by ACT) from 9 (Q1-Q3: 7–13) to 20 points (Q1-Q3: 16–23); the proportion of patients with uncontrolled SA decreased from 97.4 to 48.7% (p &lt; 0.001). The need for SABA decreased to 92.9% (p &lt; 0.001). The proportion of patients on SGCS decreased from 60.5% to 15.8% (p &lt; 0.001). The quality of life (AQLQ) significantly improved, FEV1 increased (p &lt; 0.001), the number of eosinophils in peripheral blood decreased (p = 0.015). By the end of the second year of therapy, the trend of improvement in indicators of efficacy continued.Conclusions. During 1 year of therapy with omalizumab, patients with allergic SA experienced a significant decrease in the number of exacerbations and use of health care resources, improved quality of life and asthma control, reduced need for SABA and SGCS, and improved respiratory function. In patients treated with omalizumab for 2 years, there was a further improvement or stabilization of efficacy indicators.

Calprotectin in chronic rhinosinusitis eosinophil extracellular traps.

Calprotectin is an antimicrobial peptide primarily secreted by neutrophils. Furthermore, calprotectin secretion increases in patients with chronic rhinosinusitis (CRS) with polyps (CRSwNP) and positively correlates with neutrophil markers. However, CRSwNP is known to be associated with type 2 inflammation related to tissue eosinophilia. Therefore, the authors investigated calprotectin expression in eosinophils and eosinophil extracellular traps (EETs) and explored the associations between tissue calprotectin and the clinical findings of patients with CRS. A total of 63 patients participated, and patients diagnosed with CRS were classified based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score. The authors performed hematoxylin and eosin staining, immunohistochemistry, immunofluorescence with calprotectin, myeloperoxidase (MPO), major basic protein (MBP), and citrullinated histone H3 with the participant's tissues. Finally, correlations between calprotectin and the clinical data were examined. Calprotectin-positive cells are co-localized not only in MPO-positive cells but also in MBP-positive cells in human tissues. Calprotectin was also involved in EETs and neutrophil extracellular traps. The number of calprotectin-positive cells in the tissue was positively correlated with the number of tissue and blood eosinophils. In addition, calprotectin in the tissue is associated with the olfactory function, Lund-Mackay computed tomography score, and JESREC score. Calprotectin, known to be secreted by neutrophils, in CRS was also expressed in eosinophils. In addition, calprotectin, which functions as an antimicrobial peptide, may play an important role in the innate immune response based on its EET involvement. Therefore, calprotectin expression could reflect as a disease severity biomarker for CRS.

Association of asthma genetic variants with asthma-associated traits reveals molecular pathways ofeosinophilic asthma.

Asthma is a complex, polygenic, heterogenous inflammatory disease. Recently, we generated a list of 128 independent single nucleotide polymorphisms (SNPs) associated with asthma in genome-wide association studies. However, it is unknown if asthma SNPs are associated with specific asthma-associated traits such as high eosinophil counts, atopy, and airway obstruction, revealing molecular endotypes of this disease. Here, we aim to identify the association between asthma SNPs and asthma-associated traits and assess expression quantitative trait locus (e-QTLs) to reveal their downstream functional effects and find drug targets. Association analyses between 128 asthma SNPs and associated traits (blood eosinophil numbers, atopy, airway obstruction, airway hyperresponsiveness) were conducted using regression modelling in population-based studies (Lifelines N=32,817/Vlagtwedde-Vlaardingen N=1554) and an asthma cohort (Dutch Asthma genome-wide association study N=917). Functional enrichment and pathway analysis were performed with genes linked to the significant SNPs by e-QTL analysis. Genes were investigated to generate novel drug targets. We identified 69 asthma SNPs that were associated with at least one trait, with 20 SNPs being associated with multiple traits. The SNP annotated to SMAD3 was the most pleiotropic. In total, 42 SNPs were associated with eosinophil counts, 18 SNPs with airway obstruction, and 21 SNPs with atopy. We identified genetically driven pathways regulating eosinophilia. The largest network of eosinophilia contained two genes (IL4R, TSLP) targeted by drugs currently available for eosinophilic asthma. Several novel targets were identified such as IL-18, CCR4, and calcineurin. Many asthma SNPs are associated with blood eosinophil counts and genetically driven molecular pathways of asthma-associated traits were identified.

Increased Serum Levels of Tumor Necrosis Factor-like Ligand 1A in Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic skin disease with pruritus, affecting 5-20% of the population in developed countries. Though its cause varies from genetic polymorphisms to the environmental factors, the T-helper (Th) 2 inflammation is one of the main characteristic pathoses. TNF superfamily ligand A (TL1A) is a recently discovered cytokine, which is released by various immune cells and reported to have an ability to stimulate Th1, Th2, and Th17 responses. Its association was investigated in chronic inflammatory disease, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, its role on AD is unclear. To elucidate the association of TL1A in AD, we measured the serum TL1A levels in AD patients and healthy controls and performed the immunohistochemistry of TL1A. The result showed that the serum TL1A levels were higher in AD patients than healthy controls, and they positively correlated with the serum immunoglobulin E levels, serum Lactate dehydrogenase, and the number of eosinophils in peripheral blood. The immunohistochemistry of TL1A also showed TL1A expression in epithelium of AD samples. Because previous studies indicate TL1A has a certain role as an inflammation enhancer in Th2 and/or Th17 polarized disease, TL1A in AD may also has a role as an inflammation generator.

Intestinal Protozoa (Entamoeba histolytica and Giardia lamblia ) and their effect on some Hematological Parameters in Al-Manssora Hospitals, Aden, Yemen

Intestinal protozoa are among the organisms that cause diseases in various countries of the world, especially poor countries. Six hundred and three stool samples were collected from patients coming to some hospitals in Mansoura District (22 May Hospital, Cuban Hospital, Al-Naqeeb Hospital, Al Salam Hospital), and blood samples were taken from 384 patients of both sexes infected with intestinal protozoa (E. histolytica, Giardia lamblia) and 21 blood samples from non-infected people.&#x0D; The results of the current study showed that the total infection rate of intestinal protozoa (E. histolytica, G. lamblia) was 603/384 (63.68%). For blood picture tests, a decrease in haemoglobine values and an increase in the total number of white blood cells and Eosinophils were observed for the affected people. The aim of this study is to determine the prevalence rate of E. histolytica and G. lamblia and its effect on some hematological parameters in some hospitals in Al-Mansoura District of Aden Governorate (Yemen).&#x0D; We recommend raising the level of health by providing educational programs and paying attention to personal hygiene in order to reduce the incidence of parasites, activate the role of health institutions, and work to combat rodents and insects to cut off the parasite life cycle.

Сlinical and allergological characteristics of chronic inflammatory diseases of the nose in patients with severe bronchial asthma receiving immunobiological therapy in the Sverdlovsk region

Introduction. Allergic rhinitis, chronic rhinosinusitis (with/without polyps) are chronic inflammatory diseases of the nose and often accompany asthma, aggravating its severity.Aim of the study. Тo determine the phenotypes, spectrum of sensitization and severity of chronic inflammatory diseases of the nose in patients with severe bronchial asthma receiving immunobiological therapy in the Sverdlovsk region.Materials and methods. The territorial register of adult patients with severe bronchial asthma (n = 85) who received immunobiological therapy in the Sverdlovsk region in October 2021 was analyzed. When diagnosing chronic inflammatory diseases of the nose, an examination by an otorhinolaryngologist and computed tomography of the paranasal sinuses were performed; were determined: the absolute number of blood eosinophils, specific IgE to inhaled allergens, including the FadiatopTM method; skin tests were performed; assessment of the severity of nasal symptoms was determined using the SNOT-22, VAS.Results. Chronic inflammatory diseases of the nose were reported in 89.4% of patients. Allergic rhinitis occurred in 54.1% of cases (n = 46). 54.3% (n = 25) were dominated by patients with a moderate course; severe course was observed in 28.3% of cases (n = 13). Allergic rhinitis in 92.3% of cases (n = 36) was accompanied by allergic asthma and in 71.4% (n = 10) – mixed. Sensitization to household allergens was more common, from seasonal allergens to tree pollen. Phadiatop was positive in all patients with allergic rhinitis and negative in patients with chronic rhinosinusitis with/without nasal polyps. Patients with chronic rhinosinusitis occurred in 35.3% of cases (n=30); nasal polyps were in 23.5% (n = 20). The highest rates of blood eosinophilia were in patients with concomitant chronic rhinosinusitis with nasal polyps – 920 cells/µl. This phenotype in 95% of cases was accompanied by non-allergic (eosinophilic) asthma.Conclusion. Severe bronchial asthma is almost always accompanied by chronic inflammatory diseases of the nose. Phadiatop shows its high informativeness in determining the phenotype of allergic rhinitis.

Changes in peripheral blood eosinophils may predict colorectal cancer – A retrospective study

BackgroundColorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Eosinophils are traditionally associated and studied in context of allergic diseases. However, recent data implicate their involvement in mucosal tumors, especially in CRC where they may have an anti-tumorigenic function.Our objective was to evaluate whether trends in peripheral blood eosinophil numbers are associated with future diagnosis of CRC. MethodsThis retrospective cohort study included adult patients diagnosed with CRC compared to matched controls. We evaluated the linear change in the absolute number of eosinophils (ANE) in peripheral blood over time, described as a correlation coefficient (r). The timeline started 7 years and ended 3 months before diagnosis of CRC. ResultsWe included 8334 CRC patient/control pairs. Over the study period, no linear correlation was found between levels of eosinophils and time in either group. In a subset of patients (1350, 8.1%), a positive linear correlation was found between levels of eosinophils and time. CRC was significantly more common in these patients (59% vs. 41%, p < 0.01). In a logistic regression, positive r was found to be an independent predictor for CRC (OR 1.31, 95%CI: 1.22–1.41, p < 0.001) with high specificity (0.93) but low sensitivity (0.1). ConclusionWe found higher risk for CRC in patients with a positive linear increase in peripheral eosinophils over time. This may be an indirect clue that eosinophils play a role in the pathogenesis of CRC. Linear changes in ANE may be used in the future to improve screening measures for CRC. Trial registrationNot relevant.

Severe asthma and long-term Benralizumab effectiveness in real-life.

Long-term efficacy of Benralizumab in real life is not clearly known. We assessed the long-term effectiveness persistence to anti-IL-5R treatment in a group of severe eosinophilic asthmatics. We retrospectively analyzed 95 individuals affected by severe asthma (36 males ̶ 37.9%; mean age 58.1 ± 12.2) treated with Benralizumab (mean time 19.7 ± 7.2 months, range 12-35). Outcomes were evaluated at the beginning and at the end of patients' treatment periods. Mean baseline blood eosinophils were 897.5 ± 720.1 cells/μL (11 ± 5.6%) decreasing to 7.4 ± 20.6 cells/μL (0.97 ± 0.26%; p < 0.0001) after Benralizumab. FENO likewise decreased from 63.9 ± 68.4 to 28.4 ± 23.6 ppb, while FEV1% significantly improved (p < 0.0001). Mean FEF25-75 also increased from 45.8 ± 24.6% to 60.7 ± 24.6%, whereas RAW dropped from 202.15 ± 109.6% to 135.2 ± 54.75% (p < 0.0001). Also, lung volumes greatly decreased. ACT/ACQ significantly improved, while exacerbations number fell from 4.1 ± 2.4, before anti-IL-5R, to 0.33 ± 0.77, after treatment (p < 0.0001). Rhinitis severity levels and SNOT-22 also changed favorably. Patients that took long-term OCs were 71.6% before treatment, decreasing to 23.2% after Benralizumab (p < 0.0001), with an OCs dose reduction from 14.8 ± 8.9 to 1.45 ± 2.8 mg/day (p < 0.0001). 51.6% of subjects used SABA as needed before Benralizumab, falling to 4.2% after treatment. Several patients showed a reduction of ICS doses, SABA use and maintenance therapy step-down. Clinical/biological response with anti-IL-5R remained constant or even improved in terms of exacerbations or maintenance therapy reductions over time. On the contrary, FEF25-75% improvement slowed down in the long-term. No relationship was found between baseline blood eosinophil number and therapeutic response. Long-term Benralizumab effectiveness persistence in all outcomes in real life was confirmed.

The effects of age, sex, breed, diet, reproductive status and housing condition on the amounts of 25(OH) vitamin D in the serum of healthy dogs: Reference values.

Optimal amount of vitamin D for the proper functioning of the immune system is different from the required vitamin D amount for bones to prevent rickets. However, reports on vitamin D reference values in dogs are minimal, and there is still not enough information regarding the relationship between vitamin D and various variables such as disease, age, breed, diet type, and so on, as well as its relationship with haematological and serum biochemical parameters. The present study aimed to determine reference values of 25(OH) Vit D in dogs and its concentration in different groups, categorized based on age, sex, breed, housing conditions, and diet, as well as 25(OH) Vit D relationship with hematology and serum biochemistry parameters. In this study, 90 healthy dogs were selected to determine the reference value of 25 (OH) Vit D of serum after evaluating of their haematological and biochemical parameters to assess their general health. Dogs were divided into different groups according to above-mentioned variables. Serum 25 (OH) Vit D was subsequently measured by the ELISA method. The median concentration of 25 (OH) Vit D was 52.50ng/ml with minimum and maximum amounts of 14.00 and 155.57ng/ml, respectively. No significant difference was observed between 25 (OH) Vit D levels in the studied dogs regarding their different age, sex, breed, diet, housing condition, and reproductive status. Serum 25 (OH) Vit D concentration is directly correlated with the number of band neutrophils (p<0.05). We also witnessed indirect correlations between serum 25 (OH) Vit D levels and the number of blood eosinophils and serum glucose (p<0.05). In the present study age, sex, breed, housing condition and age had no significant effects on the amounts of 25(OH) vitamin D. According to correlations of vitamin D with MCH, band and eosinophil numbers and glucose, vitamin D may have a role in erythropoiesis and leukocytes response and also in energy metabolism in dog.

Состояние факторов врожденного иммунитета у облученных лиц, впоследствии заболевших раком

Currently, cancer is the major cause of mortality and disability among the working age population of the developed countries. Early diagnosis of tumors, that involves monitoring the health of people exposed to radiation, is one of the most pressing challenges faced by radiation medicine. The study was aimed to perform quantification and functional assessment of the system of neutrophil granulocytes, monocytes and natural killers (NK cells) in people who were diagnosed with tumors after chronic radiation exposure. Certain factors of innate immunity were assessed in 104 people, chronically exposed to low-dose radiation over a wide dose range. Of them 34 exposed individuals were later diagnosed with malignant tumors (MTs). We assessed the number of white blood cells, neutrophil granulocytes, eosinophils, basophils, monocytes and NK cells (CD16+/CD56+ lymphocytes) in peripheral blood, as well as phagocytic, lysosomal activity and intracellular oxygen-dependent metabolism of neutrophils and monocytes. Individuals, chronically exposed a few years before the development of MTs, showed a significant increase in the phagocytosis rate of monocytes (median 10.50 AU vs. 6 AU; p = 0.05) and lysosomal activity of neutrophils (median 482 AU vs. 435.5 AU; p = 0.03) compared to patients with no MTs. Assessment of the the dose–response relationship in exposed people, who subsequently developed cancer, revealed a significant increase in the phagocytosis rate of monocytes as a function of the accumulated dose to thymus and peripheral lymphoid organs (ρ = 0.45; p = 0.009), and the increase in phagocytic activity of neutrophils with the increase in the accumulated dose to red bone marrow (ρ = 0.44; p = 0.01).

Dietary supplementation with sodium gluconate improves the growth performance and intestinal function in weaned pigs challenged with a recombinant Escherichia coli strain

BackgroundThe purpose of this research is to determine the effects of sodium gluconate (SG) on the growth performance and intestinal function in weaned pigs challenged with a recombinant Escherichia coli strain expressing heat-stable type I toxin (STa).ResultsPigs (n = 24, 21 days of age) were randomly allocated to three treatments: Control group (pigs were fed basal diet), STa group (pigs were fed basal diet and challenged with a recombinant E. coli strain expressing STa), and SG group (pigs were fed basal diet supplemented with 2500 mg/kg sodium gluconate and challenged with a recombinant E. coli strain expressing STa). The trial period lasted for 15 days. On days 12 and 13, pigs in the STa and SG groups were orally administered with the recombinant Escherichia coli strain, while those in the control group were orally administered with normal saline at the same volume. On day 15, blood, intestinal tissues and colonic contents were collected for further analysis. Results showed that dietary SG supplementation had a tendency to increase average daily gain, and reduced (P < 0.05) feed to gain ratio, plasma glucose concentration, and mean corpuscular hemoglobin concentration as compared with control group on days 0-10 of trial. Additionally, dietary SG supplementation attenuated(P < 0.05) the morphological abnormalities of small intestinal and the increase of the number of eosinophils in blood of pigs challenged with the recombinant Escherichia coli strain on day 15 of trial. Compared with control group, diarrhea rate and the number of eosinophils in blood and the concentrations of malondialdehyde in the jejunum were increased (P < 0.05). The height, width and surface area of the villi of the duodenum, the width and surface area of villi of jejunum and the height and width of villi of ileum were decreased (P < 0.05) in pigs challenged with the recombinant Escherichia coli strain in the STa group compared with those in control group on day 15 of trial. However, these adverse effects were ameliorated (P < 0.05) by SG supplementation in the SG group on day 15 of trial. Furthermore, dietary SG supplementation could reduce (P < 0.05) the total bacterial abundance in the colon, but SG did not restore the recombinant Escherichia coli-induced microbiota imbalance in colon.ConclusionsIn conclusion, dietary supplementation with SG could improve piglet growth performance and alleviate the recombinant Escherichia coli-induced intestinal injury, suggesting that SG may be a promising feed additive for swine.

Effects of glucocorticoids on leukocytes: Genomic and non-genomic mechanisms.

Glucocorticoids (GCs) have been widely used as immunosuppressants and anti-inflammatory agents to treat a variety of autoimmune and inflammatory diseases, and they fully exert their anti-inflammatory and immune-regulating effects in the body. The effect of GCs on white blood cells is an important part of their action. GCs can cause changes in peripheral blood white blood cell counts by regulating the proliferation, differentiation, and apoptosis of white blood cells. Although the total number of white blood cells, neutrophil counts, lymphocytes, and eosinophils increases, the counts of basic granulocytes and macrophages decreases. In addition, GCs can regulate the activation and secretion of white blood cells, inhibit the secretion of a variety of pro-inflammatory cytokines, the expression of chemokines, and promote the production of anti-inflammatory cytokines. For patients on GC therapy, the effects of GCs on leukocytes were similar to the changes in peripheral blood caused by bacterial infections. Thus, we suggest that clinicians should be more cautious in assessing the presence of infection in children with long-term use of GCs and avoid overuse of antibiotics in the presence of elevated leukocytes. GCs work through genomic and non-genomic mechanisms in the human body, which are mediated by GC receptors. In recent years, studies have not fully clarified the mechanism of GCs, and further research on these mechanisms will help to develop new therapeutic strategies.

Activation of STAT6 by intranasal allergens correlated with the development of eosinophilic chronic rhinosinusitis in a mouse model.

Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease characterized by prominent eosinophilic infiltration along with a T-helper-2 (Th2) response. It has been well documented that signal transducer and activator of transcription 6 (STAT6) is a nuclear transcription factor that mediates Th2-type immunity and is implicatory of STAT1 and STAT3 in the pathogenesis of allergic airway diseases. However, little is known about the association between STATs and ECRS. Here, we explored the relationship between STAT1, STAT3, and/or STAT6 and eosinophilic inflammation accompanied by Th2-type immunity in a mouse model of ECRS. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was first established. The mucosal histological alterations were determined using hematoxylin and eosin staining. The number of eosinophils in peripheral blood was measured using a blood cell analyzer. The cytokine (IL-4, IL-5, IL17 A and IFN-γ) expression levels in the sinonasal mucosa and total and OVA-specific IgE from serum were measured using ELISA. Then, the protein levels of STAT1, STAT3, STAT6, phosphorylated STAT1 (p-STAT1), p-STAT3, p-STAT6, T-box expressed in T-cells (T-bet), GATA binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor γ (RORγt) in the sinonasal mucosa were examined by immunohistochemical staining or Western blotting. Local administration of OVA combined with SEB (OVA + SEB) induced multiple polyp-like lesions, accompanied by prominent eosinophilic infiltration in the sinonasal mucosa. The OVA- and OVA+SEB-treated groups showed significantly higher eosinophil counts from peripheral blood and total and OVA-specific IgE levels from serum than those in the PBS- and SEB-treated groups. The levels of p-STAT6 were markedly increased by OVA + SEB exposure, as well as GATA-3, IL-4, and IL-5, but did not affect STAT6, p-STAT1, p-STAT3, T-bet, RORγt, IFN-γ, or IL-17A. Furthermore, an eosinophil count in the sinonasal mucosa showed a positive correlation with the level of p-STAT6 in the ECRS mouse model. Signal transducer and activator of transcription 6 signaling could be activated in the OVA+SEB-induced ECRS model and might be a crucial signal transducer in the development of Th2-skewed ECRS.

Efficacy of anti-IL-5 therapy with mepolizumab for severe bronchial asthma and concomitant inflammatory nasal diseases in real clinical practice

BACKGROUND. T2 inflammation underlies non-allergic eosinophilic severe bronchial asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Existing targeted anti-IL-5 drugs can improve clinical and functional parameters in patients with a combination of severe asthma and CRSwNP.&#x0D; AIM: to evaluate mepolizumab efficacy in patients with non-allergic severe asthma and concomitant inflammatory nasal diseases (CIND) in real clinical practice.&#x0D; MATERIALS AND METHODS. The study was conducted without a control group, by comparing related populations (before-after analysis) and based on the Sverdlovsk regional register of adult patients with severe asthma and CIND. The primary endpoint was asthma control achievement (ACT questionnaire) and decrease in the proportion of patients with uncontrolled severe asthma. The number of asthma exacerbations, emergency calls and hospitalizations, quality of life according to AQLQ questionnaire, peripheral blood eosinophils level and respiratory function (FEV1, FVC, FEV1/FVC) were also assessed. Dynamics of nasal symptoms was assessed using SNOT22 questionnaire and visual analogue scale (VAS).&#x0D; RESULTS. During 12 months of therapy with mepolizumab, ACT increased from 9 (Q1-Q3: 7-11) to 22 points (Q1-Q3: 21-24) (p0.001). The proportion of patients with uncontrolled asthma decreased from 100% to 10% (p0.001). The number of asthma exacerbations decreased from 3.182.8 per patient per year to 0 (p0.001) and hospitalizations from 0.570.9 per patient per year to 0 (p=0.007). Quality of life according to AQLQ increased from 3.481.05 (95% CI 2.734.24) to 5.590.88 (95% CI 4.966.22) points (p0.001). The number of blood eosinophils decreased from 442 (Q1-Q3: 336-853) to 90 (Q1-Q3: 73-117) cells/l (p0.001). There was increase in FEV1 from 63.9%24.2 (95% CI 46.681.2) to 80.5%18.3 (95% CI 67.493.6) (p=0.015). There was decrease in SNOT22 questionnaire score by 33 points (from 4530 to 2215) (p=0.006) and decrease in VAS score by 5 points (from 8 (Q1-Q3: 5-8) to 3 (Q1-Q3: 3-5)) (p=0.017).&#x0D; CONCLUSIONS. According to the study results, there were asthma control improvement, asthma exacerbations decrease, quality of life improvement according to AQLQ. Statistically significant peripheral blood eosinophils decrease and respiratory function improvement were also revealed. In patients with CIND, significant improvement in nasal breathing was noted, which was confirmed by scores of SNOT22 and VAS questionnaires.

Principles of modern diagnosis and treatment of atopic dermatitis and bronchial asthma: Clinical case

This article presents the experience of successful use of the drug dupilumab in a patient with severe atopic dermatitis and bronchial asthma. The effectiveness of biological therapy with dupilumab 300 mg subcutaneously for 52 weeks of T-2 associated diseases, including a combination of severe atopic dermatitis and bronchial asthma, uncontrolled course based on the case history of patient Ts., born in 2006 with the diagnosis "Main: atopic dermatitis, common form, severe course. Concomitant diagnosis: bronchial asthma, persistent course, uncontrolled, moderate severity". Dynamic monitoring of the total blood count with the calculation of the absolute number of eosinophils in peripheral blood was performed. The study showed high efficacy and safety of biological therapy with dupilumab 300 mg subcutaneously every 2 weeks for 52 weeks with a combination of severe atopic dermatitis and bronchial asthma, uncontrolled course in patient Ts (Born in 2006). The examination of the ALEX2 allergochip made it possible to establish the molecular components of the primary causal allergens, predict the course of an allergic disease, and carry out successful elimination measures against food allergens, preserving the maximum set of nutrients in the patient's diet. Dupilumab therapy in severe atopic dermatitis and uncontrolled bronchial asthma leads to clinically significant improvement in the course of diseases, control of disease symptoms. Atopic dermatitis shows a decrease in itching of the skin, normalization of sleep, improvement of quality of life. With bronchial asthma, a reduction in exacerbations, normalization of respiratory function indicators, complete control of the disease has been achieved. The targeted biological drug dupilumab has a targeted effect on the key links in the pathogenesis of atopic dermatitis and bronchial asthma and reduces the burden of severe diseases. Therefore, the use of dupilumab in atopic dermatitis and bronchial asthma contributes to achieving disease control and improving the patient's quality of life.

ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study

BackgroundData from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness.MethodsANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only.ResultsOf 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400–850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5–25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1–13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (− 93.3%) and to 0.06 for severe exacerbations (− 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0–10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index.ConclusionsWe described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA.Trial registration ClinicalTrials.gov Identifier: NCT04272463

Critical roles of interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) in pulmonary disorders.

Critical roles of interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) in pulmonary disorders.

АСТМА-ХОЗЛ ПЕРЕХРЕСТ: БАГАТО ВЖЕ ВІДОМО, АЛЕ ЧАСТИНА ЗАПИТАНЬ ЩЕ ЗАЛИШАЄТЬСЯ БЕЗ ВІДПОВІДЕЙ

The review is devoted to topical issues of terminology, diagnostic criteria and principles of therapy for a pathological condition known as “Asthma-COPD overlap”. Specialists in the field of pulmonology have got used to such term as “Astma- COPD overlap” (ACO), but till now the nuances of diagnostics and treatment of such patients are not developed. The prevalence of ACO in the population varies within 2–55 %. This discrepancy is due, first of all, to the absence of clearly defined criteria of the ACO. Nowadays, the prevailing view is that the ACO is a state characterized by persistent air flow limitation with several signs usually associated with asthma or COPD. This is not a definition of a single disease, but a description term for clinical use, which includes several different clinical phenotypes. The risk of ACO is that the patients have frequent exacerbations, higher mortality, fast lung function decline and worse quality of life. For the purpose of diagnosis of ACO, it is recommended to use the large criteria (persistent airflow limitation (post-bronchodilation FEV1/FVC &lt; 0.7 or the lower limit of normal) in patients aged 40 years and older, with at least 10 pack-years of tobacco smoking or equivalent exposure to indoor or outdoor air pollution, documented history of asthma under 40 years or post-bronchodilation Δ FEV1 &gt; 400 ml) and small criteria (documented history of atopy or allergic rhinitis, post-bronchodilation ΔFEV1 &gt; 200 ml and 12% of baseline values during 2 or more visits, the number of eosinophils in the peripheral blood ≥ 300 cells per μl). Patients with ACO should use therapy containing inhaled corticosteroids (ICS), as this reduces the risk of their hospitalization and death compared to long-term treatment only with bronchodilators. Availability of ACO requires review of planned therapy for patients who previously had asthma or COPD diagnosis only. If COPD is accompanied by asthma, patients should be prescribed ICS as soon as possible. When asthma is accompanied by COPD and at the same time the patient is already taking ICS and long-acting beta-agonists, then long-acting M-cholinolytics should also be considered. Research in the field of the diagnosis and treatment of ACO continues, as some questions are still to be answered. Key words: asthma, chronic obstructive pulmonary disease, asthmaCOPD overlap, diagnosis, treatment.