A novel risk score for disease control prediction of Chronic rhinosinusitis

Objectives: To assess the impact of risk factors on the disease control among CRS patients, following 1 year of functional endoscopic sinus surgery (FESS), and combining the risk factors to formulate a convenient, visualized prediction model. Design: A retrospective and nonconcurrent cohort study Setting and Participants: A total of 325 patients with Chronic rhinosinusitis (CRS) from June 2018 to July 2020 at the First Affiliated Hospital, the Third Affiliated Hospital, and the Seventh Affiliated Hospital of Sun Yat-sen University. Main Outcomes Measures: Outcomes were time to event measures: the disease control of CRS after surgery 1 year. The presence of nasal polyps, smoking habits, allergic rhinitis (AR), the ratio of tissue eosinophil (TER), and peripheral blood eosinophil count (PBEC)and asthma was assessed. The logistic regression models were used to conduct multivariate and univariate analyses. Asthma, TER, AR, PBEC were also included in the nomogram. The calibration curve and AUC (Area Under Curve) were used to evaluate the forecast performance of the model. Results: In univariate analyses, most of the covariates had significant associations with the endpoints, except for age, gender, and smoking. The nomogram showed the highest accuracy with an AUC of 0.760 (95% CI, 0.688-0.830) in the training cohort. Conclusions: In this cohort study that included the asthma, AR, TER, PBEC had significantly affected the disease control of CRS after surgery. The model provided relatively accurate prediction in the disease control of CRS after FESS and served as a visualized reference for daily diagnosis and treatment.

Peripheral blood eosinophil count is associated with response to chemoimmunotherapy in metastatic triple-negative breast cancer

Introduction: There is evidence for an association between peripheral blood eosinophil count (PBEC) and response to cancer immunotherapy; however, such data is limited in metastatic triple-negative breast cancer (mTNBC). Patients & methods: This report presents patients (n = 14) who received a combination of durvalumab and paclitaxel for mTNBC (NCT02628132). Results: There was a statistically significant correlation (p = 0.028) between an increase in PBEC (>300/mm3) during treatment and response to the combination therapy. Survival analysis showed a statistically significant association between progression-free survival and increased PBEC, after therapy (p = 0.005). A similar trend existed for overall survival, although it did not reach statistical significance (p = 0.167). Conclusion: This is the first study to report on eosinophilia in mTNBC treated with chemoimmunotherapy and supports a role for eosinophils in immunotherapy for mTNBC.

Predicting In-hospital Death in Pneumonic COPD exacerbation via BAP-65, CURB-65, and Machine Learning

IntroductionThere is no established clinical prediction model for in-hospital death among patients with pneumonic chronic obstructive pulmonary disease (COPD) exacerbation. We aimed to externally validate BAP-65 and CURB-65 and to develop a new model based on the eXtreme Gradient Boosting (XGBoost) algorithm.MethodsThis multicentre cohort study included patients aged ≥40 years with pneumonic COPD exacerbation. The input data were age, sex, activities of daily living, mental status, systolic and diastolic blood pressure, respiratory rate, heart rate, peripheral blood eosinophil count, and blood urea nitrogen. The primary outcome was in-hospital death. BAP-65 and CURB-65 underwent external validation using the area under the receiver operating characteristic curve (AUROC) in the whole dataset. We used XGBoost to develop a new prediction model. We compared the AUROCs of XGBoost with that of BAP-65 and CURB-65 in the test dataset using bootstrap sampling.ResultsWe included 1190 patients with pneumonic COPD exacerbation. The in-hospital mortality was 7% (88/1190). In the external validation of BAP-65 and CURB-65, the AUROCs (95% confidence interval [CI]) of BAP-65 and CURB-65 were 0.69 (0.66–0.72, and 0.69 (0.66–0.72), respectively. XGBoost showed an AUROC of 0.71 (0.62–0.81) in the test dataset. There was no significant difference in the AUROCs of XGBoost versus BAP-65 (absolute difference, 0.054; 95% CI, −0.057–0.16) or versus CURB-65 (absolute difference, 0.0021; 95% CI, −0.091–0.088).ConclusionBAP-65, CURB-65, and XGBoost showed low predictive performance for in-hospital death in pneumonic COPD exacerbation. Further large-scale studies including more variables are warranted.

Association of IL33, IL1RL1, IL1RAP Polymorphisms and Asthma in Chinese Han Children

Background: Genome-wide association studies have identified interleukin 33 (IL33), interleukin 1 receptor-like 1 (IL1RL1), interleukin 1 receptor accessory protein (IL1RAP) as asthma susceptibility loci in Europeans. IL33, IL1RL1, and IL1RAP constitute a ligand-receptor complex.Objective: We analyzed associations of asthma susceptibility, eosinophilic airway inflammation, and response to inhaled corticosteroid (ICS) with single nucleotide polymorphisms (SNPs) of 3 genes encoding IL33, IL1RL1, and its coreceptor IL1RAP in Chinese Han nationality children.Methods: A total of 153 non-asthmatic children and 265 asthmatic children who visited the Xiangya Hospital between September 2015 and August 2019 were recruited for this study. Pulmonary function tests, peripheral blood eosinophil counts (PBEC), and fractional exhaled nitric oxide (FeNO) tests were performed before treatment, and 3 months after treatment. Each participant’s DNA was extracted from the peripheral blood, and a Mass ARRAY system was used to genotype the SNPs.Results: The T allele of rs4742170 in IL33 was associated with a risk of higher FeNO at baseline, and no improvement in FeNO and airway hyperresponsiveness was found after ICS treatment. The A allele of rs10208293 and C allele of rs13424006 in IL1RL1 both were associated with lower susceptibility to asthma and lower FeNO. The TT genotype of rs1420101 and AA genotype of rs4142132 in IL1RL1 were associated with a greater probability of improvement in PBEC after ICS treatment.Conclusion: IL33-IL1RL1-IL1RAP complex polymorphisms are associated with childhood asthma susceptibility, eosinophilic airway inflammation, and ICS response in Chinese Han children in Hunan. We speculate that IL33-IL1RL1-IL1RAP complex polymorphisms affect the development of asthma, airway inflammation, and subsequent ICS response in childhood.

The Correlation of Peripheral Blood Eosinophils with Allergic Nasal Polyps

Aim: To observe the association of peripheral blood eosinophil percentage in patients with allergic nasal polyps. Design: Descriptive cross-sectional study Place and duration: Pathology Department of Bakhtawar Amin Medical & Dental Hospital, Multan from September 2020 to August 2021. Methodology: Blood samples of all the cases operated for nasal polyps in Bakhtawar Amin Trust Institute are drawn before surgery to look for eosinophils. Family and past history of allergy is recorded. Histopathology of all the operated specimen of nasal polyps is done and sample for eosinophil count is collected again in cases that proved to be allergic nasal polyps on microscopic examination to look for any alteration in eosinophil percentage in blood on excision of polyps. Results: Twenty nine out of forty (72.5) percent of patients with allergic nasal polyps reveal increase in peripheral blood eosinophil percentage that returned to normal in 26(65%) patient on excision of nasal polyps. Conclusion: The study disclosed a notable link between allergic nasal polyps and peripheral blood eosinophil percentage and this association is further enhanced by the fact that the blood eosinophil count returned to normal on removal of nasal polyps. Keywords: Allergic nasal polyps, peripheral blood eosinophilia, eosinophil count, atopy

Exercise Training Induces a Shift in Extracellular Redox Status with Alterations in the Pulmonary and Systemic Redox Landscape in Asthma

Redox dysregulation and oxidative stress have been implicated in asthma pathogenesis. Exercise interventions improve symptoms and reduce inflammation in asthma patients, but the underlying mechanisms remain unclear. We hypothesized that a personalised exercise intervention would improve asthma control by reducing lung inflammation through modulation of local and systemic reactive species interactions, thereby increasing antioxidant capacity. We combined deep redox metabolomic profiling with clinical assessment in an exploratory cohort of six female patients with symptomatic asthma and studied their responses to a metabolically targeted exercise intervention over 12 weeks. Plasma antioxidant capacity and circulating nitrite levels increased following the intervention (p = 0.028) and lowered the ratio of reduced to oxidised glutathione (p = 0.029); this was accompanied by improvements in physical fitness (p = 0.046), symptoms scores (p = 0.020), quality of life (p = 0.046), lung function (p = 0.028), airway hyperreactivity (p = 0.043), and eosinophilic inflammation (p = 0.007). Increased physical fitness correlated with improved plasma antioxidant capacity (p = 0.019), peak oxygen uptake and nitrite changes (p = 0.005), the latter also associated with reductions in peripheral blood eosinophil counts (p = 0.038). Thus, increases in “redox resilience” may underpin the clinical benefits of exercise in asthma. An improved understanding of exercise-induced alterations in redox regulation offers opportunities for greater treatment personalisation and identification of new treatment targets.

Successful induction treatment of bullous pemphigoid using reslizumab: a case report

Background Bullous pemphigoid (BP) is a potentially life-threatening autoimmune blistering disease which is characterized by autoantibodies against hemidesmosomal proteins of the skin and mucous membranes. In recent years, the role of eosinophil and immunoglobulin E autoantibodies have been further elucidated in BP, and have been considered potential therapeutic targets. Case presentations A 67-year-old male presented with erythematous bullous eruption. The skin eruption was located on whole body, and suggested BP. Peripheral blood eosinophil count and total immunoglobulin E markedly elevated in initial laboratory findings. Topical and systemic steroid (methylprednisolone 2 mg/kg/day) treatment was started, and his skin symptoms worsened repeatedly, whenever systemic steroid were reduced. On admission day 29, reslizumab (anti-interleukin-5) 3.5 mg/kg was administered intravenously to the patients. The bullous skin lesion began to improve rapidly, and methylprednisolone (8 mg/day) was reduced without any worsening of symptoms during two doses of reslizumab. Conclusions We report a case of successful treatment response to reslizumab administration in a patient with BP. Further studies are needed to confirm the role of anti-interleukin-5 as a treatment for BP in the future.

Peripheral Blood Eosinophil Count Optimizes Pembrolizumab-Based Immunotherapy in The First-Line Setting of Advanced or Recurrent Non-Small Cell Lung Cancer

For cancer immunotherapy, the tumor proportion score for the programmed death-1 ligand is not a robust biomarker. The peripheral blood eosinophil count (PEC) is a potential alternative. However, it is not yet established. To test the efficacy of PEC-guided selection of pembrolizumab monotherapy (MONO) or pembrolizumab plus chemotherapy (COMBO), we retrospectively reviewed data of patients with advanced or recurrent non-small cell lung cancer in the first-line setting (April 2017 to April 2020). Among 137 patients enrolled, Kaplan–Meier analysis revealed no significant difference between the MONO (n = 84) and COMBO (n = 53) therapies. The influence of PEC before the second administration of each regimen (PEC2) was evaluated. The low PEC2 subgroup (<150 × 106/L) receiving MONO had poorer survival rates than those receiving COMBO (median progression-free survival [mPFS]: 5.75 vs. 7.59 months and median overall survival [mOS]: 12.0 months vs. not reached [NR), respectively). In patients receiving MONO, the low PEC2 showed worse prognosis compared with the high PEC2 group (mPFS: 5.75 vs. 16.1 months and mOS: 12.0 months vs. NR, respectively). PEC2 can be a potential predictive/prognostic biomarker for MONO, which encourages the switch from MONO to COMBO to avoid treatment failure.

Real-Life Effectiveness of Mepolizumab on Forced Expiratory Flow between 25% and 75% of Forced Vital Capacity in Patients with Severe Eosinophilic Asthma

Severe eosinophilic asthma (SEA) is associated with high peripheral blood and airway eosinophilia, recurrent disease exacerbations and severe airflow limitation. Eosinophilic inflammation is also responsible for small airway disease (SAD) development. SEA patients experience poor disease control and response to standard therapy and are prime candidates for anti-IL5 biologicals, such as mepolizumab, but the effect of treatment on SAD is unclear. We investigated the effect of mepolizumab on lung function in SEA patients, focusing on SAD parameters, and searched for an association between patients’ phenotypic characteristics and changes in small airways function. In this real-life study, data from 105 patients with SEA were collected at baseline and after 6, 12 and 18 months of mepolizumab treatment. Along with expected improvements in clinical and lung function parameters brought by Mepolizumab treatment, FEF2525-75% values showed a highly significant, gradual and persistent increase (from 32.7 ± 18.2% at baseline to 48.6 ± 18.4% after 18 months) and correlated with ACT scores at 18 months (r = 0.566; p ≤ 0.0001). A patient subgroup analysis showed that changes in FEF25-75% values were higher in patients with a baseline peripheral blood eosinophil count ≥400 cells/μL and oral corticosteroid use. Mepolizumab significantly improves small airway function. This effect correlates with clinical benefits and may represent an accessible parameter through which to evaluate therapeutic response. This study provides novel insights into the phenotypic characteristics associated with the improved functional outcome provided by mepolizumab treatment.

Study of Eosinophil Count in Nasal and Peripheral Blood Smear Compare with Serum IgE Level in Children with Allergic Rhinitis

Introduction: Allergic rhinitis is one of the most common respiratory diseases. Patient with allergic rhinitis may have elevated level of serum IgE and eosinophil than normal person. Nasal smear eosinophil count is a simple test as well as noninvasive, can be repeated and inexpensive method for diagnosis of allergic rhinitis. Objective: To assess the eosinophil count in nasal smear as an alternative diagnostic test for children with allergic rhinitis. Methods: This cross-sectional study was conducted at the Department of Laboratory medicine and Paediatrics, BSMMU, Dhaka from September 2019 to August 2020 in 120 children (Age up to 18 years both sex). Diagnosed patients of allergic rhinitis according to ARIA-WHO guideline with history and clinical feature who fulfilled the inclusion criteria were selected as study population. After taking informed written consent blood and nasal secretion of allergic patient were drawn for serum IgE and eosinophil count. Nasal smears for eosinophil were stained using Giemsa stain and observed eosinophil under light microscope. Peripheral blood eosinophil count was estimated by hematology auto-analyzer (SYSMEX-XN 2000) and rechecked manually. The serum total IgE level was performed based on sandwich principle of ELISA. Results: The serum IgE level, nasal smear eosinophil count and blood eosinophil count were found increased with severity of allergic rhinitis, which was statistically significant (p<0.001). Pearson’s correlation coefficient test revealed significant positive correlation between nasal smear eosinophil count with serum IgE (r= +.656, p<0.001) and blood absolute eosinophil count (r= +.415, p<0.001). Conclusion: Nasal smear eosinophil count was significantly raised alone with absolute eosinophil count and serum IgE level with the severity of allergic rhinitis in children.