Lower Eosinophil Research Articles

Pediatric infection with the Omicron variant increases the risks of febrile seizures among COVID-19 infected children.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is less likely to cause severe disease in children than the other variants but has become an increasing cause of febrile seizures (FS) among children. In this case-control study, we aimed to examine the risk factors associated with FS in children infected with the COVID-19 Omicron variant and related treatment modalities. This retrospective case-control study includes 113 subjects infected with the COVID-19 Omicron variant, grouped into 45 cases (those with FS) and 68 controls (those without FS). Data on clinical features, laboratory parameters, and treatment modalities were collected and analyzed. Approximately 5.74% of COVID-19 infected children developed COVID-19-associated FS. Children with COVID-19 and high body temperatures [RR 1.474; (95% CI: 1.196-1.818), p < 0.001], previous history of FS [RR 1.421; (95% CI: 1.088-1.855), p = 0.010], high procalcitonin levels [RR 1.140; (95% CI: 1.043-1.246), p = 0.048] and high neutrophil counts [RR 1.015; (95% CI: 1.000-1.029), p = 0.048] were more likely to experience FS than the controls. In contrast, children with COVID-19 and low eosinophil counts, low hemoglobin levels, and cough had a lower risk of developing FS [RR 0.494; (95% CI: 0.311-0.783), p = 0.003], [RR 0.979; (95% CI: 0.959-0.999), p = 0.044]; and [RR 0.473 (95% CI 0.252-0.890), p = 0.020]; respectively. Children with FS received more anti-flu medications than those without. A significant increase in FS was observed in children with Omicron SARS-CoV-2 infection. A higher body temperature, a history of FS, a higher procalcitonin level, and a high neutrophil count were all associated with an increased risk of FS in children with COVID-19. The risk of developing FS was lower in children with COVID-19 and low eosinophil counts and hemoglobin levels than in those without.

Prognosis Predictive Markers in Patients with Chronic Obstructive Pulmonary Disease and COVID-19.

Some studies have reported that chronic respiratory illnesses in patients with COVID-19 result in an increase in hospitalization and death rates, while other studies reported to the contrary. The present research aims to determine if a predictive model (developed by combing different clinical, imaging, or blood markers) could be established for patients with both chronic obstructive pulmonary disease (COPD) and COVID-19, in order to be able to foresee the outcomes of these patients. A prospective observational cohort of 165 patients with both diseases was analyzed in terms of clinical characteristics, blood tests, and chest computed tomography results. The beta-coefficients from the logistic regression were used to create a score based on the significant identified markers for poor outcomes (transfers to an intensive care unit (ICU) for mechanical ventilation, or death). The severity of COVID-19, renal failure, diabetes, smoking status (current or previous), the requirement for oxygen therapy upon admission, high lactate dehydrogenase (LDH) and C-reactive protein level (CRP readings), and low eosinophil and lymphocyte counts were all identified as being indicators of a poor prognosis. Higher mortality was linked to the occurrence of renal failure, the number of affected lobes, the need for oxygen therapy upon hospital admission, high LDH, and low lymphocyte levels. Patients had an 86.4% chance of dying if their mortality scores were -2.80 or lower, based on the predictive model. The factors that were linked to a poor prognosis in patients who had both COPD and COVID-19 were the same as those that were linked to a poor prognosis in patients who had only COVID-19.

Prognostic Value of Routine Biomarkers in the Early Stage of COVID-19.

Various biomarkers like certain complete blood cell count parameters and the derived ratios including neutrophil-lymphocyte ratio are commonly used to evaluate disease severity. Our study aimed to establish if baseline levels of complete blood cell count-derived biomarkers and CRP, measured before any treatment which can interfere with their values, could serve as a predictor of development of pneumonia and the need for hospitalization requiring oxygen therapy. We retrospectively analyzed the laboratory data of 200 consecutive patients without comorbidities, who denied usage of medications prior to blood analysis and visited a COVID-19 ambulance between October and December 2021. Multivariate regression analysis extracted older age, elevated CRP and lower eosinophil count as significant independent predictors of pneumonia (p = 0.003, p = 0.000, p = 0.046, respectively). Independent predictors of hospitalization were higher CRP (p = 0.000) and lower platelet count (p = 0.005). There was no significant difference in the neutrophil-lymphocyte and platelet-lymphocyte ratios between examined groups. Individual biomarkers such as platelet and eosinophil count might be better in predicting the severity of COVID-19 than the neutrophil-lymphocyte and platelet-lymphocyte ratios.

Confirmation Of African Swine Fever Virus in Some Pigs from Ado Local Government Area of Benue State, Nigeria

Studies were undertaken to investigate and isolate African Swine Fever virus in pig in Ado local government area (LGA) of Benue state of Nigeria and this has confirmed the carrier status of the pigs in the LGA. Out of the 188 serum samples collected, 7 were obtained from the LGA and were tested using Enzyme Linked Immunosorbent Assay (ELISA). Three samples (42.86%) were positive and 4(57.14%) were negative for the test. All the serum samples (42.86%) that were positive by ELISA were also positive by polymerase chain reaction amplification (PCR). The PCR-positive pigs had higher mean WBC count, lower eosinophil and basophils count, higher mean monocytes count but the mean PCV values were not significantly different from the normal and PCR negative pigs. High mean WBC count may indicate an ongoing secondary bacterial and ASF virus infection, lower eosinophil and basophils count indicates parasitism in the pigs, higher mean monocytes count. This confirmed that pigs with demonstrable antibody should be considered as chronic carriers of the virus because it is doubtful if true recovery ever occurs. Control measures such as use of biosecurity, test and slaughter of animals that test positive for African Swine Fever (ASF) antibody with adequate compensation are suggested to eradicate the disease.

An overview of the preclinical discovery and development of tezepelumab for the treatment of asthma

ABSTRACT Introduction Tezepelumab is a human IgG2 monoclonal antibody (mAb) that binds to human thymic stromal lymphopoietin (TSLP), preventing its interaction with the receptor and inhibiting multiple downstream inflammatory pathways. TSLP is an alarmin relevant to the pathogenesis of asthma. Areas covered This article focuses on the significance of TSLP in developing asthma and how tezepelumab can target it, thus playing a potentially relevant role in the treatment of asthma. Expert opinion An extensive clinical development program has shown that tezepelumab can improve all key primary and secondary endpoints in patients with severe asthma, compared to placebo, when added to standard therapy. Of particular importance is the favorable impact of this biological drug on exacerbation rates and lung function in patients with uncontrolled severe asthma regardless of the type 2 endotype. Therefore, tezepelumab is likely the first biologic to treat asthma exacerbations in patients with low eosinophil levels successfully. Furthermore, it appears to be a safe drug and can be ‘self-administered’ using a pre-filled, disposable pen. Tezepelumab should be preferred over other currently available biologics because blocking upstream mediators may have a broader therapeutic impact than those that inhibit downstream cytokines and/or block their receptors.

Peripheral blood eosinophil count as a biomarker of exacerbation in stable chronic obstructive pulmonary disease outpatients: a prospective observational study

Abstract Background Peripheral blood eosinophil count is liable to many factors and has variability over time. There are few studies on the association between the rise of blood eosinophils and the exacerbation incidence in stable chronic obstructive pulmonary disease (COPD) patients. The association between the rise of blood eosinophils and the rate of exacerbation in stable COPD patients is controversial. Objective To study the relationship between the count of eosinophils in the peripheral blood and the incidence of COPD exacerbation in stable patients. Patients and methods This prospective inquiry was done on 46 patients diagnosed as suffering from stable COPD ‘on the report of the global initiative for chronic obstructive lung disease (GOLD) guidelines’ attending Ain Shams University hospital outpatient clinic. Results Forty-six stable COPD patients were classified into two groups (groups A and B) based on their median eosinophilic count of ‘250 cell/μl.’ Patients with high eosinophil count ‘group A’ (&gt;250 cell/μl) had a significantly higher incidence of exacerbations (P=0.003), with a relative risk ratio of 2.77, as well as a higher number of exacerbations per patient (two exacerbations/patient) versus one exacerbation/three patients (P&lt;0.001), and a shorter period to the first exacerbation (17 vs. 31 days) (P=0.024), compared with those with low eosinophil count ‘group B (≤250 cell/μl)’ during the study period. On the contrary, there was no significant difference between them in the incidence of pneumonia in relation to inhaled corticosteroid use. Conclusion The count of eosinophils in the peripheral blood is a reliable exacerbation biomarker in stable COPD patients.

Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus.

The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value.

Brusellozlu Hastalarda Bakteriyeminin Makine Öğrenmesi Yöntemleri Kullanılarak Tahmin Edilmesi

Purpose: The correct and early diagnosis of brucellosis is very crucial to decelerate its spread and providing fast treatment to patients. This study aims to develop a predictive model for diagnosing bacteremia in brucellosis patients based on some hematological and biochemical markers without the need for blood culture and bone marrow and to investigate the importance of these markers in predicting bacteremia.&#x0D; Materials/Methods: 162 patients with diagnosing brucellosis, 54.9% of whom are non-bacteremic, 45.1% bacteremia were retrospectively collected. The 20 demographic, hematological and biochemical laboratory parameters and 30 classifiers are used to predict bacteremia in brucellosis. Classifiers were developed by using Python programming language. Accuracy (ACC), Area under the receiver operating characteristic curve (AROC), and F measure were employed to find the best fit classification method. Feature importance method was used to determine most diagnostic markers to predict the bacteremia. Results: Extratree classifier with criterion “entropy” (ETC1) showed the best predictive performance with Acc values ranging between 0.5 and 1.00, F values between 0.53 and 1, and AROC values between 0.62 and 1. The neutrophil%, lymphocyte%, eosinophil%, alanine aminotransferase, and C-reactive protein were determined as the most distinguishing features with the scores 0.723, 1.000, 0.920, 0.869, and 0.769, respectively.&#x0D; Conclusions: This study showed that the ETC1 classifier may be helpful in determining bacteremia in brucellosis patients and that elevated lymphocytes, alanine aminotransferase, and C-reactive protein and low neutrophils and eosinophils may indicate bacteremic brucellosis.

White blood cell count profiles in anti-aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder and anti-myelin oligodendrocyte glycoprotein antibody-associated disease

White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with these diseases within three months from an attack before acute treatment or relapse prevention and compared the profiles with those in matched volunteers or in multiple sclerosis (MS) patients. AQP4-NMOSD patients (n = 13) had a higher neutrophil count (p = 0.0247), monocyte count (p = 0.0359), MLR (p = 0.0004), and NLR (p = 0.0037) and lower eosinophil (p = 0.0111) and basophil (p = 0.0283) counts than those of AQP4-NMOSD-matched volunteers (n = 65). Moreover, patients with MOGAD (n = 26) had a higher overall WBC count (p = 0.0001), neutrophil count (p < 0.0001), monocyte count (p = 0.0191), MLR (p = 0.0320), and NLR (p = 0.0002) than those of MOGAD-matched volunteers (n = 130). The three demyelinating diseases showed similar levels of the total and differential WBC counts; however, MOGAD and MS showed different structures in the hierarchical clustering and distributions on a two-dimensional canonical plot using differential WBC counts from the other three groups. WBC count profiles were similar in patients with MOGAD and MS but differed from profiles in matched volunteers or patients with AQP4-NMOSD.

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.

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia.

Transforming growth factor-β-associated kinase 1 (TAK1) mediates non-canonical TGF-β signalling by promoting adhesive, migratory, proliferative and contractile responses of fibroblasts to TGF-β1. However, TAK1 expression status in asthmatic patients with or without fixed airway obstruction (FAO) is unknown. A total of 60 adult asthmatics with FAO were recruited and compared to 43 those without FAO (nFAO). TGF-β1 concentrations, and total TAK1 and phosphorylated TAK1 (p-TAK1) levels were determined in sputum supernatants, cytospin, and whole cell lysate by ELISA, immunocytochemistry, and Western blot analysis, respectively, in asthmatics with and without FAO. Asthmatic patients with FAO had much greater sputum TGF-β1 concentrations than those without FAO. This was independent of airway eosinophilia as there was no significant difference in TGF-β1 levels between high and low eosinophil counts within FAO and nFAO groups. In contrast, patients with FAO in the presence of sputum eosinophilia had greater expression of TAK1 and p-TAK1 than those without sputum eosinophilia (P=0.0032 and P=0.0061, respectively). The Western Blot data of total TAK1 and p-TAK1 were consistent with the immunocytochemistry, showing upregulation in all sputum cell types (neutrophils, eosinophils, macrophages, lymphocytes and airway epithelial cells). In addition, total TAK1 expression negatively correlated with pre- and post-bronchodilator FEV1/FVC ratio. TAK1 may play a key role in asthmatic patients with fixed airway obstruction, which was independent of eosinophilic airway inflammation. The interruption of TAK1 might have favourable clinical impact.

Anti-epithelial-derived cytokines for severe asthma: Systematic review and meta-analysis

Therapies directed against epithelial-derived cytokines, often referred to as alarmins, have been studied in large randomized trials, and reports suggest possible benefit for non-type 2 as well as type 2 severe asthma. We performed a systematic review of Medline, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process, and Web of Science databases from inception to March 2022. We performed a random-effects pairwise meta-analysis of randomized controlled trials addressing antialarmin therapy in severe asthma. Results use relative risk (RR) values and 95% confidence intervals (CIs). For continuous outcomes, we report mean difference (MD) values and 95% CIs. We define high eosinophils as ≥300 cells/μL and low eosinophils as <300 cells/μL. We used Cochrane-endorsed RoB 2.0 software to assess the risk of bias of trials, and we used the Grades of Recommendation Assessment, Development, and Evaluation (aka GRADE) framework to assess the certainty of the evidence. We identified 12 randomized trials including 2391 patients. Antialarmins probably reduce annualized exacerbation rates in patients with high eosinophils (RR 0.33 [95% CI 0.28 to 0.38]; moderate certainty). Antialarmins may reduce this rate in patients with low eosinophils (RR 0.59 [95% CI 0.38 to 0.90]; low certainty). Antialarmins improve FEV1 in patients with high eosinophils (MD 218.5 mL [95% CI 160.2 to 276.7]; high certainty). Antialarmin therapy probably does not improve FEV1 in patients with low eosinophils (MD 68.8 mL [95% CI 22.4 to 115.2]; moderate certainty). Antialarmins reduce blood eosinophils, total IgE, and fractional excretion of nitric oxide across studied subjects. Antialarmins are effective at improving lung function and probably reduce exacerbations in patients with severe asthma and blood eosinophils ≥300 cells/μL. The effect on patients with lower eosinophils is less certain.

Risk factors for adverse outcomes in elderly patients with asthma and severe COVID-19 at the hospital and early post-hospital stages

Mortality and COVID-19 related factors are thoroughly analyzed. Given the large number of hospitalized patients, the potential short- and long-term COVID-19 related complications, further research is needed on the possible consequences of hospitalization, especially in higher-risk patients, after prolonged hospitalization and intensive care admission. To study the clinical course and outcomes of severe COVID-19 in elderly patients with asthma at the hospital and early post-hospital stages. The study included 131 elderly patients (WHO, 2020) >60 years old, n=131 with asthma, hospitalized for severe COVID-19. Of these, 86 (65.6%) patients survived, 30 (22.9%) died in the hospital, and 15 (14.9%) patients died after discharge from the hospital (in the 90-day post-hospital period). COVID-19 was confirmed by laboratory tests (SARS-CoV-2 PCR RNA test) and/or clinically and radiologically. All patients had a documented history of asthma. Patients were followed up during the hospital stay and for 90 days after discharge. Comparison of outcomes showed that in the groups of patients with a fatal outcome (regardless of the stage), the Charlson comorbidity index, respiratory rate, extent of lung damage assessed by computed tomography, the absolute leukocyte and neutrophil number and the ratio of neutrophils to lymphocytes were statistically significantly higher. The absolute number of eosinophils was lower in these groups. In the group of patients who died during hospitalization, severe (IV-V) asthma (p=0.03), steroid use during the previous year (p=0.02), chronic heart failure with a reduced ejection fraction (p=0.009) were more common, and atopic asthma phenotype was less common (p=0.02). In those who died after discharge, more common were non-invasive ventilation and diabetes mellitus (p<0.001). The multivariate regression analysis model revealed the most significant predictors of mortality at the hospital and early post-hospital stages. Adverse outcomes of severe COVID-19 in elderly patients with asthma include hospital and post-hospital mortality. The most significant predictors of mortality are the comorbidity index and low eosinophil count. Hospital mortality is associated with a higher ratio of neutrophils to lymphocytes and lower total protein levels; early (90-day) post-hospital mortality is associated with extensive lung damage shown by computed tomography and diabetes mellitus.

Analysis of severity and evaluation of prognosis in elderly patients with bronchial asthma and severe COVID-19

Introduction. The role of comorbid conditions in susceptibility to SARS-CoV-2 infection and the severity of associated COVID-19 disease has been an area of ongoing research since the pandemic began.Objective. To evaluate the impact of elderly asthma on the clinical course and outcomes of severe COVID-19.Materials and methods. Elderly patients (WHO, 2020) (&gt; 60 years, n = 131) with bronchial asthma (BA) hospitalized for severe COVID-19 were included in the study. The presence of COVID-19 was confirmed by laboratory tests (PCR smear) and/or clinical and radiological examinations. All patients had a history of a confirmed diagnosis of bronchial asthma (GINA, 2020). Follow-up was performed at the hospital stage and for 90 days after discharge from the hospital.Results. In the groups of patients with lethal outcome (regardless of the stage) there were statistically significantly higher Charlson index, respiratory rate, CT lung lesion volume, leukocyte, neutrophil and neutrophil to lymphocyte ratios, lower absolute eosinophil count. In the group of patients who died during hospitalization, severe (IV–V) asthma (p = 0.03), steroid use during the previous year (p = 0.02), chronic heart failure (p = 0.009), and the atopic asthma phenotype was less common (p = 0.02). Those who died in the 90-day posthospital period had greater lung lesion volume on CT scan, and diabetes mellitus was more common (p &lt; 0.001). The most significant predictors of mortality were identified.Conclusion. The common most significant predictors of hospital and 90-day posthospital mortality in older patients with bronchial asthma were comorbidity index and lower eosinophil levels. Hospital mortality is further characterized by a higher neutrophil to lymphocyte ratio and lower total protein; 90-day posthospital mortality by the amount of lung damage on CT scan and the presence of diabetes mellitus.

Peripheral Eosinophil Count Associated with Disease Activity and Clinical Outcomes in Hospitalized Patients with Lupus Nephritis

Introduction: The aim of this study was to evaluate the association of peripheral eosinophil (EOS) count with disease activity and kidney outcomes in lupus nephritis (LN) patients. Methods: A total of 453 hospitalized and biopsy-proven LN patients at our hospital from 2006 to 2013 were enrolled, of which 388 patients had repeated measurements of EOS. Relationships were explored between average EOS and disease activity at baseline, using the systemic lupus erythematosus disease activity (SLEDAI) and activity index (AI) on kidney biopsy. Follow-up data were available through December 2016. The primary outcome measure was a composite of doubling of serum creatinine and end-stage kidney disease after a median follow-up of 51 months. Results: The mean age of the enrolled 388 LN patients was 33.1 ± 10.8 years old, and 335 (86%) were female. The median average peripheral EOS count was 0.033 (0.015–0.057) ×10⁹/L. Mean AI and SLEDAI score were 6.8 ± 2.5 and 14.9 ± 5.4, respectively. Logistic regression models showed that decreased average EOS was independently associated with higher AI (≥6) and higher SLEDAI (≥15) (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90–0.97; and OR 0.96, 95% CI: 0.93–0.99, respectively). There was a parabolic relationship between average EOS and the primary outcome, with hazard ratio (HR) > 1 for both levels ≤0.033 and >0.16 × 10⁹/L. Conclusion: Lower EOS count was independently associated with severe disease activity and kidney progression in LN.

A Retrospective Claims Database Study to Clarify Disease Burden of Severe Asthma Patients with Type 2 High or Low Inflammation

The disease burden of severe asthma patients stratified by type 2 (T2) biomarkers is not well studied in large patient samples, especially for T2-low severe asthma patients. Using a Japanese medical record database, we investigated disease and economic burdens in T2-high and T2-low severe asthma patients. Data of severe asthma patients (receiving high-dose inhaled corticosteroids and additional asthma-related controller medications or oral corticosteroids [OCS] prescription [≥183 days] during the 1-year baseline period) were analyzed in the Real World Data database, comprising electronic medical records from Japanese medical institutions. Severe asthma patients were stratified into a T2-high population with higher eosinophils (≥150 cells/μL) and/or higher total immunoglobulin E (IgE, ≥75 IU/mL) or a T2-low population with lower eosinophils (<150 cells/μL) and lower total IgE (<75 IU/mL). The incidence of asthma exacerbation events and drug costs were analyzed for each population. Different T2 thresholds were explored, including eosinophil count 300 cells/μL and/or IgE 150 IU/mL. Of the 732 severe asthma patients, 599 (81.8%) patients had T2-high type, and 133 (18.2%) had T2-low type. Proportions of the T2-high patients (30.6%) with asthma exacerbations, defined as a composite outcome, including OCS burst, injectable steroid use, and hospitalization, were similar to those of T2-low type (34.6%). The annual drug cost was similar between T2-high (175,487 JPY) and T2-low (165,322 JPY) populations. In this large-scale study, both T2-high and T2-low severe asthma patients in Japan were shown to have a high disease burden and high economic burden, suggesting an unmet treatment need.

Activity of the inflammatory process depending on sputum markers in children with different onset of bronchial asthma

Aim of the study: To analyse the activity of the inflammatory process in the airways in children with bronchial asthma depending on the onset of the disease. Materials and methods: In compliance with the principles of bioethics, a comprehensive retrospective examination of 319 children suffering from bronchial asthma was performed. In 257 children (clinical group I), bronchial asthma developed on the background of chronic obstructive bronchitis. The second (II) clinical group included 43 children, in whom asthma occurred after community-acquired pneumonia. The third (III) clinical group consisted of 19 children in whom asthma was first verified after inpatient treatment for asthmatic status. Results: Based on the severity of bronchial asthma, it was found that the representatives of the clinical group III, compared with other patients, significantly more often had a severe course of the disease. For patients of the clinical group I, the onset was characterised by increased eosinophils and decreased neutrophil counts in sputum, for group II patients – increased eosinophils and epitheliocytes, but a decrease in lymphocytes, and in children of the clinical group III – low eosinophils in the sputum with a simultaneous increase in neutrophils. In particular, a statistically significant increase in the level of vascular endothelial growth factor, and a decrease in the content of cationic proteins, matrix metalloproteinase-9, and interleukins 6 and 13, in sputum indicates the predominance of neoangiogenesis in children of the clinical group III. Instead, in the clinical group II the remodelling processes were mainly caused by the inflammatory process with the release of intracellular eosinophilic cationic proteins. Conclusion: These data indicate the discrete nature of the type and severity of the inflammatory process of the respiratory tract over the dynamic follow-up period in children classified in different clinical comparison groups, which suggests the presence of certain phenotypic differences due to alternative onsets of the disease, which were determined by different triggers. Such deviations in the inflammatory process indicate that patients with asthma require a personalised approach to ensure differentiated diagnostic monitoring and targeted anti-inflammatory treatment, taking into account the peculiarities of the onset of the disease.

Blood eosinophil count variability in chronic obstructive pulmonary disease and severe asthma

BackgroundBlood eosinophils are essential biomarkers that vary substantially over time in patients with COPD and asthma. However, no study has identified the changes and effects in the changes of the blood eosinophil counts over time in both diseases. This study aimed to demonstrate blood eosinophil variability in patients with COPD and severe asthma based on these backgrounds. MethodsA total of 172 patients with COPD from the Hokkaido COPD cohort study and 96 patients with severe asthma from the Hokkaido Severe Asthma Cohort Study, whose blood eosinophil counts were measured annually over a 3-year period, were analyzed. The factors contributing to consistently high or low blood eosinophil counts were examined in each cohort. The stability of the eosinophil classification (<150, 150–299, ≥300 cells/μL) was compared based on the number of asthma-like features in patients with COPD and the smoking status in patients with severe asthma. ResultsAmong all the patients, the most stable range of baseline blood eosinophil counts differed between the two diseases, with <150 cells/μL in COPD and ≥300 cells/μL in severe asthma. In COPD, the number of asthma-like features (bronchodilator reversibility, blood eosinophilia, and atopy) affects the blood eosinophil count variation patterns. In severe asthma, smoking status did not affect the blood eosinophil count variation patterns. ConclusionsWe identified variations in the blood eosinophil counts and their contributing factors in patients with COPD and severe asthma.

A comparison of the effectiveness of biologic therapies for asthma: A systematic review and network meta-analysis

BackgroundTrials have not directly compared biologics for the treatment of asthma. ObjectiveTo compare the relative efficacy of biologics in asthma. MethodsWe searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to May 31, 2022 for randomized trials addressing biologic therapies for asthma. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. We present dichotomous outcomes as absolute risk differences per 1000 patients and relative risk with 95% confidence intervals (95% CI) and continuous outcomes as mean difference (MD) and 95% CI. ResultsWe identified 64 trials, including 26,630 patients. For patients with eosinophilic asthma, tezepelumab (329 fewer exacerbations per 1000 [95% CI, 272.6-366.6 fewer]) and dupilumab (319.6 fewer exacerbations per 1000 [95% CI, 272.6-357.2 fewer]) reduce exacerbations compared with placebo (high certainty). Tezepelumab (MD, 0.24 L [95% CI, 0.16-0.32]) and dupilumab (0.25 L [95% CI, 0.21-0.29]) improve lung function compared with placebo (high certainty). Both tezepelumab (110.97 fewer hospital admissions per 1000 [95% CI, 94.53-120.56 fewer]) and dupilumab (97.27 fewer hospitalizations [4.11-124.67 fewer]) probably reduce hospital admissions compared with placebo (moderate certainty). For patients with low eosinophils, biologics probably do not improve asthma outcomes. For these patients, tezepelumab (MD, 0.1 L [95% CI, 0-0.19]) and dupilumab (MD, 0.1 L [95% CI, 0-0.20]) may improve lung function (low certainty). ConclusionTezepelumab and dupilumab are effective at reducing exacerbations. For patients with low eosinophils, however, clinicians should probably be more judicious in using biologics, including tezepelumab, because they probably do not confer substantial benefit.

Nationwide survey of refractory asthma with bronchiectasis by inflammatory subtypes

RationaleBronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control.ObjectiveWe determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them.MethodsWe conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed.ResultsIn total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO.ConclusionsBronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.