Blood Eos Research Articles

Real-world biomarker variability and effects of biologics on severe asthma in Alberta

Rationale: Guidelines recommend biomarker testing to phenotype patients with severe asthma (SA), to guide treatment. However, biomarker levels fluctuate, and individual responses to biologics are not fully understood. Objectives: This study estimated the proportion of patients experiencing biomarker variability and the real-world effectiveness of biologics in SA. Methods: A population-based retrospective cohort study was conducted using administrative data from Alberta, Canada (April 1, 2010 to March 31, 2020) for patients with SA. Year-to-year variability in biomarker levels was assessed using clinical thresholds (blood eosinophil count [EOS] ≥ 300 cells/µL; immunoglobin E [IgE] ≥ 30 IU/mL) to explore category switching. Incidence rate ratios of exacerbations were estimated by biomarker level. Associations between follow-up time with biologics exposure (bio-experience), biomarker levels and exacerbation rates were modeled. Results: Up to 28% of SA patients displayed year-over-year biomarker threshold switching for EOS and up to 12% for IgE. Severe exacerbation rates were higher with blood EOS count ≥300cells/µL or IgE ≥30 IU/mL. Bio-experience was associated with lower blood EOS versus pre-bio-experience (relative mean EOS: 0.53 [0.42-0.68]), persisting >1 year following discontinuation. Bio-experience was associated with a nearly 50% reduction in exacerbation risk after initiating biologics (IRR = 0.54 [0.48, 0.62]), regardless of comorbid status. Conclusions: Higher biomarker levels were associated with higher exacerbation rates, but a proportion of patients demonstrated variability, crossing clinical thresholds. Treatments with upstream agents targeting multiple pathways of inflammation may circumvent this issue. Biologics had real-world effectiveness in reducing SA biomarkers. Their persistent temporal effect provides a groundwork for exploring cost-effective biologics use.

Blood eosinophilia and a higher ethmoid sinus/maxillary sinus score ratio predict new-onset asthma in patients with chronic rhinosinusitis with nasal polyps

Backgroud Presently, the impact of Chronic rhinosinusitis with nasal polyps (CRSwNP) on asthma onset is unknown. Aims To evaluate the role of CRSwNP in asthma onset. Materials and Methods A total of 3107 CRSwNP patients were retrospectively screened from 1 January 2018, to 31 May 2021; 624 patients were enrolled. Clinical data regarding nasal symptoms, Lund-Mackay scores, blood eosinophil percentage, and onset of asthma were analyzed. Patients were divided into different groups according to past history of nasal polyps, Lund-Mackay score, and the extent of blood eosinophilia. Asthma-free rates between these subgroups were analyzed by Kaplan–Meier curves and Cox regression models. Results The prevalence of asthma was 10.90% in patients with CRSwNP, and new-onset asthma occurred in 3.14% of these patients. Higher Lund-Mackay scores for ethmoid sinus and maxillary sinus (E/M) and blood eosinophil percentages were two independent risk factors for new-onset asthma, with hazard ratios of 1.267 (95%CI, 1.155–1.390) and 1.224 (95%CI, 1.054–1.422), respectively. CRSwNP patients with an E/M ratio > 2.33 or a blood Eos percentage > 5.5% were at risk for asthma onset. Conclusions and significance Blood eosinophilia and a higher E/M score ratio were associated with new-onset asthma in patients with CRSwNP.

The value of combined detection of specific immunoglobulin E, interleukin-6 and regulatory T cells in predicting the risk of postoperative recurrence in patients with eosinophilic chronic rhinosinusitis and nasal polyps.

To investigate the predictive value of specific immunoglobulin E (sIgE), interleukin-6 (IL-6) and regulatory T cells (Treg) on the risk of postoperative recurrence in patients with eosinophilic Chronic rhinosinusitis with nasal polyps (EcRswNP). A total of 198 patients with EcRswNP collected to our Hospital from January 2019 to December 2021 were selected as the research subjects. All patients underwent functional endoscopic sinus surgery. The patients were selected to recurrence group (RG, n = 48) and nonrecurrence group (NRG, n = 150) on the basis of the recurrence after 1 year of follow-up. The related factors of postoperative recurrence of EcRswNP were analyzed. The ROC was used to analyze the dangerous of sIgE, IL-6 and Treg in predicting postoperative recurrence of EcRswNP patients. The proportion of asthma patients, nasal congestion VAS score, and peripheral blood Eos% content in the RG exceeded that in the NRG, and the Organization Neu % and peripheral blood Neu% levels were less than those in the NRGp (P all < 0.05). The serum sIgE and serum IL6 in the RG were higher than those in the NRG, while the level of peripheral blood Treg was lower than that in the NRG (P < 0.05). Logistic regression analysis showed that high levels of serum sIgE, serum IL-6 and low Treg levels were risk factors for postoperative recurrence (P < 0.05). ROC showed that the AUC of peripheral blood sIgE level, IL-6 and Treg levels alone in predicting the dangerous of postoperative recurrence in patients with EcRswNP were 0.786, 0.707 and 0.636, respectively (all P < 0.05); The AUC of combined prediction of peripheral blood sIgE, IL-6 and Treg levels for postoperative recurrence dangerous in patients with EcRswNP was 0.973, indicating that the efficacy of jointed prediction was exceed than that of single prediction (P < 0.05). The high levels of sIgE, IL6 and low Treg levels in patients with EcRswNP before operation will increase the risk of postoperative recurrence, which is a risk factor affecting postoperative recurrence, and the three indicators have good predictive value for predicting postoperative recurrence in patients with EcRswNP, and the combination of the three indicators has better value in predicting postoperative recurrence.

Experience of clinicians with dual bronchodilator therapy in COPD (EXPAND) in Nepal

Introduction: Combination of bronchodilators, particularly long-acting muscarinic antagonists (LAMAs) and long-acting β2 agonists (LABAs) have become the mainstay of pharmacological therapy for COPD. COPD is now a common non communicable disease in Nepal. Objective: The study evaluated the current perception and experience of the clinicians in Nepal on diagnosis and management of COPD with focus on use of dual bronchodilator therapy. Method: This cross-sectional, observational survey evaluated experiences of clinicians (n=96; pulmonologist-13, physician-57, general practitioner-26) in Nepal on diagnosis, management trends, and current perceptions on the use of dual bronchodilator therapy in COPD management. Result: 93% of clinicians were practising in an urban setting for an average of 10 years and an average of 35% of their patients are of COPD. 61% of clinicians use mMRC with (34%) or without (27%) CAT score. 92% of clinicians perceived that most of their patients had 1 (32%) or &gt;1 (59%) exacerbation/year. 54% of clinicians performed spirometry on all their patients with suspected COPD. 49% of clinicians measured blood EOS in their patients with severe COPD before adding ICS. 93% of clinicians preferred dual therapy (separate inhalers or a combination) for their COPD patients, but 83% of clinicians preferred LABA + LAMA in a single inhaler over inhalers given separately. 57% of clinicians preferred LABA + LAMA and 82% preferred the Tiotropium + Formoterol combination. 81% of clinicians stepped up or stepped down their treatment. 56% of patients were taking LABA + LAMA + ICS and 55% of clinicians co-prescribed ICS + LABA with LABA + LAMA. 80% of clinicians checked the inhalation technique at every visit and an average of 54% of their COPD patients were adherent (&gt;80%) to the prescribed inhalation therapy. 78% of clinicians felt that dryness of mouth was the most common side effect of LABA + LAMA. 94% of clinicians believed that managing COPD better could improve cardiovascular outcomes in their patients with coexistent COPD. Conclusion: In the EXPAND survey, Formoterol + Tiotropium was preferred by most clinicians in Nepal amongst the LABA + LAMA combination. There is a good scope for improvement in the utilization of tools like spirometry, mMRC, CAT, and blood EOS in the daily practice of clinicians in Nepal.

Development and Validation of Prediction Models for Exacerbation, Frequent Exacerbations and Severe Exacerbations of Chronic Obstructive Pulmonary Disease: A Registry Study in North China

In COPD patients, exacerbation has a detrimental influence on the quality of life, disease progression and socioeconomic burden. This study aimed to develop and validate models to predict exacerbation, frequent exacerbations and severe exacerbations in COPD patients. We conducted an observational prospective multicenter study. Clinical data of all outpatients with stable COPD were collected from Beijing Chaoyang Hospital and Beijing Renhe Hospital between January 2018 and December 2019. Patients were followed up for 1 year. The data from Chaoyang Hospital was used for modeling dataset, and that of Renhe Hospital was used for external validation dataset. The final dataset included 456 patients, with 326 patients as the model group and 130 patients as the validation group. Using LABA + ICS, frequent exacerbations in the past year and CAT score were independent risk factors for exacerbation in the next year (OR = 2.307, 2.722 and 1.147), and FVC %pred as a protective factor (OR = 0.975). Combined with chronic heart failure, frequent exacerbations in the past year, blood EOS counts and CAT score were independent risk factors for frequent exacerbations in the next year (OR = 4.818, 2.602, 1.015 and 1.342). Using LABA + ICS, combined with chronic heart failure, frequent exacerbations in the past year and CAT score were independent risk factors for severe exacerbations in the next year (OR = 1.950, 3.135, 2.980 and 1.133). Based on these prognostic models, nomograms were generated. The prediction models were simple and useful tools for predicting the risk of exacerbation, frequent exacerbations and severe exacerbations of COPD patients in North China.

Serum interleukin-33 combined with FEF75% z-score and FeNO improves the diagnostic accuracy of asthma in children

ObjectiveTo investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. Methods132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. Results(1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. ConclusionSerum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.

Differences in the lipid metabolism profile and clinical characteristics between eosinophilic and non-eosinophilic acute exacerbation of chronic obstructive pulmonary disease.

Objective: In this study, we aimed to investigate the differences in serum lipid metabolite profiles and their relationship with clinical characteristics between patients with eosinophilic and non-eosinophilic AECOPD. Methods: A total of 71 AECOPD patients were enrolled. Eosinophilic AECOPD was defined as blood EOS% ≥ 2% (n = 23), while non-eosinophilic AECOPD, as blood EOS< 2% (n = 48). Clinical data were collected, and serum lipid metabolism profiles were detected by liquid chromatography-mass spectrometry (LC-MS). The XCMS software package was used to pre-process the raw data, and then, lipid metabolite identification was achieved through a spectral match using LipidBlast library. Differences in lipid profiles and clinical features between eosinophilic and non-eosinophilic groups were analyzed by generalized linear regression. The least absolute shrinkage and selection operator (LASSO) was applied to screen the most characteristic lipid markers for the eosinophilic phenotype. Results: Eosinophilic AECOPD patients had less hypercapnic respiratory failures, less ICU admissions, a shorter length of stay in the hospital, and a lower fibrinogen level. In the lipid metabolism profiles, 32 significantly different lipid metabolites were screened through a t-test adjusted by using FDR (FDR-adjusted p < 0.05 and VIP> 1). Nine differential lipid metabolites were found to be associated with the three clinical features, namely, hypercapnia respiratory failure, ICU admission, and fibrinogen in further integration analysis. The species of triacylglycerol (TAG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and diacylglyceryl trimethylhomoserine (DGTS) were high in these eosinophilic AECOPD. The LASSO was applied, and three lipid metabolites were retained, namely, LPC (16:0), TAG (17:0/17:2/17:2), and LPC (20:2). The logistic regression model was fitted using these three markers, and the area under the ROC curve of the model was 0.834 (95% CI: 0.740-0.929). Conclusion: Patients with eosinophilic AECOPD had a unique lipid metabolism status. Species of TAGs and LPCs were significantly increased in this phenotype and were associated with better clinical outcomes.

Characteristics of patients with severe asthma in primary and secondary care settings considered eligible for biological therapy - the Bulgarian RECOGNISE study.

Asthma is a major non-communicable disease. It affects both children and adults, but is the most common chronic condition among the former. While inhaled controller drugs stabilize the disease in most asthma patients, there are a certain number of people who suffer from severe asthma, which requires treatment escalation. Oral corticosteroids are usually added, but they are associated with various side effects that may limit their application. The introduction of biologicals targeting inflammatory mediators has opened a new era of asthma treatment highlighting the importance of patient characterization.

Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma

BackgroundWhether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA.MethodsNinety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis.ResultsThe median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05).ConclusionsMontelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar.Trial registration ClinicalTrials.gov, number NCT01404013.

Effect of moxibustion combined with Guifu Yuhe decoction on the conversion score of idiopathic constitution, serum total lgE and blood EOS in the patients with allergic acne

To observe the therapeutic effect of moxibustion combined with Guifu Yuhe decoction on allergic acne and the influence on immunologic function in the patients. A total of 60 patients with allergic acne were rando-mized into an observation group (30 cases) and a control group (30 cases).Thirty healthy employees were in the healthy group. In the control group, Guifu Yuhe decoction was prescribed for oral administration, while in the observation group, on the base of the treatment as the control group, moxibustion was exerted at Dazhui (GV14) and Shenque (GV8). The treatment duration was 8 weeks. Before and after treatment, serum IgE, blood EOS, CD4+T cell, CD8+ T cell and CD4+T/CD8+T, as well as the conversion score of idiopathic constitution and the symptom score were compared in the patients of two groups. The clinical therapeutic effect was observed in the two groups. Before treatment, compared with the healthy group, IgE and EOS, CD4+T cell and CD8+T cell all increased (P<0.05), and CD4+T/CD8+T decreased in the two groups (P<0.05). After treatment, IgE, EOS and CD4+T cell and CD8+T cell decreased (P<0.05), and CD4+T/CD8+T increased (P<0.05) in the intra-group comparison in the patients. The changes of IgE, EOS, CD4+T cell and CD8+T cell in the observation group were more larger than those in the control group (P<0.05). After treatment, the conversion score of body constitution and symptom score all decreased in either group (P<0.05) and the scores in the observation group were lower than those of the control group (P< 0.05). The total effective rate of the observation group (29/30, 96.7%) was higher than that of the control group (22/30, 73.3%, P<0.05). Moxibustion combined with Guifu Yuhe decoction can significantly improve immune function and body constitution of the patients with allergic acne, which may be related to rectifying idiopathic constitution, improving in lymphocyte subsets dysfunction and inhibiting allergic reaction.

Study on the correlation between eosinophils and chronic rhinosinusitis with nasal polyps in Xinjiang region of China

Objective: To explore the correlation between eosinophils (Eos) and the incidence of chronic sinusitis with nasal polyps (CRSwNP) in Xinjiang region of China by comparing the proportion of inflammatory cells in the pathological tissues and peripheral blood. Methods: Retrospective analysis was performed on 582 patients with CRSwNP who underwent endoscopic nasal surgery in the First Affiliated Hospital of Xinjiang Medical University from January 2012 to March 2018, including 367 males and 215 females, aged (45.5±13.4) years (x¯±s). Patients were divided into groups according to demographic characteristics, recurrence and complication of allergic rhinitis (AR). Preoperative blood routine and postoperative pathological section data of nasal polyps were collected to compare the ratio of inflammatory cells in pathological tissue and the ratio of peripheral blood Eos in each group. The correlation between the proportion of inflammatory cells in the pathological tissue of nasal polyps and the recurrence of CRSwNP was analyzed, as well as the distribution of (eosCRSwNP) in Uygur and Han CRSwNP patients in Xinjiang region. Statistical analysis was performed by SPSS 19.0 software. Results: Compared with non-recurrent CRSwNP patients, the ratio of Eos in nasal polyp tissue and peripheral blood was increased significantly, (Z value was -3.142 and -2.344, respectively, both P<0.05). Compared with CRSwNP patients without AR, the ratio of Eos in nasal polyps and peripheral blood was also increased significantly in patients with AR (Z value was -6.664 and -4.520, respectively, both P<0.05). There was a positive correlation between tissue Eos and CRSwNP recurrence (r=0.130, P=0.002). The majority of CRSwNP patients were both eosCRSwNP in Uygur and Han ethnic groups. Conclusions: Eos is associated with the recurrence of CRSwNP in Xinjiang region, and eosCRSwNP is the dominant factor in both Uygur and Han patients.

Serum Glycerophospholipid Profile in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Studies have shown that glycerophospholipids are involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study adopted targeted metabolomic analysis to investigate the changes in serum glycerophospholipids in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and their differential expression in patients with different inflammatory subtypes. Patients with AECOPD admitted between January 2015 and December 2017 were enrolled, and their clinical data were collected. The patients’ gender, age, body mass index, and lung function were recorded. Routine blood and induced sputum tests were performed. Liquid chromatography-mass spectrometry was used to detect the serum glycerophospholipid metabolic profiles and to analyze the metabolic profile changes between the acute exacerbation and recovery stages as well as the differences between different inflammatory subtypes. A total of 58 patients were hospitalized for AECOPD, including 49 male patients with a mean age of 74.8 ± 10.0 years. In the metabolic profiles, the expression of lysophosphatidylcholine (LPC) 18:3, lysophosphatidylethanolamine (LPE) 16:1, and phosphatidylinositol (PI) 32:1 was significantly reduced in the acute exacerbation stage compared to the recovery stage (P < 0.05). The three glycerophospholipids were used to plot the receiver operating characteristic curves to predict the acute exacerbation/recovery stage, and the areas under the curves were all above 70%. There were no differential metabolites between the two groups of patients with blood eosinophil percentage (EOS%) ≥2% and <2% at exacerbation. The expression of LPC 18:3, LPE 16:1, and PI 32:1 was significantly reduced in the acute exacerbation stage compared to the recovery stage in the inflammatory subtype with blood EOS <2% (P < 0.05). Abnormalities in the metabolism of glycerophospholipids may be involved in the onset of AECOPD, especially in the non-eosinophilic subtype.

A Nomogram Combing Peripheral Parameters for Estimation of CRSwNP Recurrence

The preoperative prediction of the recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP) remains difficult in clinical practice. We aimed to develop a nomogram that combined peripheral risk factors to clinically predict the recurrence of CRSwNP. Data from 158 CRSwNP patients who underwent endoscopic sinus surgery (ESS) from January 2012 to December 2016 were collected, and the patients were followed up for 3 years. Of these, 96 patients who underwent ESS in an earlier period formed the training cohort for nomogram development, and 62 patients who underwent ESS thereafter formed the validation cohort to confirm the model's performance. Risk factors for recurrence identified by univariate and multivariate logistic regression were used to create a nomogram. The recurrence rate was 29.2% (28/96) for the training cohort and 35.5% (22/62) for the validation cohort. Univariate analysis identified blood eosinophils (Eos), serum IgE level, asthma comorbidity, and the number of previous ESSs as risk factors for recurrence. Among those four parameters, serum IgE level and a previous ESS surgery were identified as two independent risk factors. A nomogram consisting of blood Eos, total serum IgE level, asthma comorbidity, and the number of previous ESSs was constructed, demonstrating a C index of 0.81 (95% CI, 0.79-0.83) and 0.80 (95% CI, 0.77-0.83) for predicting recurrence in the training and validation cohorts, respectively. The nomogram had well-fitted calibration curves. The nomogram might be able to preoperatively predict the recurrence of CRSwNP by using currently available and objective parameters. Further studies are required to validate its reliability and effectiveness.

Biomarkers of airways inflammation in patients with severe asthma in a real clinical practice

Severe asthma is a heterogeneous disease consisting of several endotypes and phenotypes diagnosed due to different biomarkers. Frequency of different endotypes and phenotypes in real clinical practice needs further investigation.The aim of this study was to assess biomarkers of T2-inflammation in patients with severe asthma in a single secondary care center.Methods. We examined 96 adult outpatients (34% male) with severe asthma. Data collected included demographics, smoking history, asthma exacerbations during previous 12 months, medication use, comorbidities. Lung function tests were assessed by using the Spirograph 2120 (Vitalograph, Great Britain). Blood eosinophils (Eos) were measured by automatic haemoanalyser. Atopic status was determined by positive skin prick-test (&gt; 3 mm) and/or serum specific IgE to common inhalant allergens. Serum total IgE levels were assessed by immunofluorescence assay. FeNO was measured by a chemiluminescence analyzer (Model LR4000; Logan Research, Rochester, UK). Presence of allergy, need for regular oral steroid use, blood Eos ≥ 150 cell/μl and FeNO ≥ 20 ppb were considered as markers of T2-driven inflammation. Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and St. George's Respiratory Questionnaire (SGRQ). Statistical analyses were performed with Statistica Ver. 10.0 (StatSoft, Inc., USA).Results. The majority of patients with severe asthma (93%) have at least one or more elevated markers (presence of allergy, need for regular oral steroid use, Eos ≥ 150 cell/μl or FeNO ≥ 20 ppb) of T2-inflammation. Biomarkers levels did not differ in non-steroid-dependent and steroid-dependent patients. The most frequent markers were allergy and blood Eos ≥ 150 cell/μl. Two or more elevated biomarkers were revealed in 72% of patients.Conclusion. The majority of patients with severe asthma in real clinical practice have signs of T2-inflammation. It seems that many severe asthmatics have indications for prescription of biological and can be treated by more than one of monoclonal antibodies against major cytokines of T2-inflammation.

Safety comparison of omalizumab and glucocorticoid in rush allergen immunotherapy

Objective:To observe the safety of omalizumab and glucocorticoid in the dose-increasing phase of rush allergen immunotherapy（RIT）. Method:The clinical data of 88 patients with allergic rhinitis treated with RIT were retrospectively studied, including gender, age, pre-treatment total VAS score, blood EOS%, serum total IgE, local and systemic adverse reactions. Of all patients, fifty-seven were treated with omalizumab combined with RIT（experimental group） and thirty-one were treated with hormone/antiallergic drugs combined with RIT（control group）. The safety of the two groups was compared in the dose-increasing phase. Result:There was no grade Ⅰ systemic adverse reactions during the whole process in the experimental group, while Grade Ⅱ systemic adverse reactions were 4 cases（7.1%） during the period of hospitalization, 2 cases（3.6%） after the first injection after discharge, zero（0） after the second injection after discharge. No local pruritus and induration were observed. During the period of hospitalization, the first and second injection after discharge, control group had grade Ⅰ level systemic adverse reactions were 1 case（3.4%）, 2 cases（6.9%）, 1 case（3.4%） at different time point, respectively. Grade Ⅱ systemic adverse reactions were 5 cases（17.2%）, 1 case（3.4%）, zero（0） at different time point, respectively. Local injection site itching was observed in 8 patients（5 cases were mild and 3 cases were moderate） and 4 cases（13.8%） had induration during hospitalization. Conclusion:Omalizumab combined with RIT not only shortens the duration of dose-increasing phase of specific immunotherapy, but also increases the safety of the dose-increasing phase during hospitalization, the first and second injection after discharge and improves patient compliance.

Application of Clinical Scores in the Differential Diagnosis of Chronic Rhinosinusitis With Nasal Polyps in a Chinese Population.

Background Eosinophilic (Eos) and non-eosinophilic (non-Eos) chronic rhinosinusitis with nasal polyps (CRSwNP) react differently to clinical treatment, with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) being more likely to recur after surgery. Objective To explore the clinical value of the visual analog scale (VAS), nasal endoscopy score (Lund–Kennedy, L–K), computed tomography (CT) score (Lund–Mackay scoring system, L–M), and blood Eos percentage in the differential diagnosis of Eos CRSwNP and non-Eos CRSwNP. Methods Ninety-nine patients with CRSwNP were enrolled in this study and assigned to 2 groups (Eos CRSwNP and non-Eos CRSwNP). The blood Eos percentage and VAS, L–K, and L–M scores in the 2 groups of patients were compared. A receiver operating characteristic (ROC) was used to assess the usefulness of VAS, L–K, and L–M scores for differentiating Eos CRSwNP and non-Eos CRSwNP. Results There were significantly differences between the Eos CRSwNP group and non-Eos CRSwNP group in the following scores: blood Eos percentage, mean VAS score, olfaction/VAS, general discomfort/L–K, edema score/L–K, olfactory cleft (OC) score via endoscopy, mean L–M score, anteriorethmoid sinus score, posterior ethmoid sinus score, sphenoid sinus score, frontal sinus score, and OC score via CT. An ROC analysis showed that blood Eos percentage had the highest area under the ROC curve (AUC) value (0.749); however, several other scores (olfaction score/VAS, edema score/L–K, and mean L–M score) also had high AUC values. The combination of olfaction score/VAS and blood Eos percentage had the highest clinical convenience score as well as high sensitivity and specificity. A combination of cutoff values for the 2 predictors (blood Eos percentage ≥3.85%, olfaction score/VAS score ≥3) showed a sensitivity of 75.5% and a specificity of 78.0%. Conclusion The olfaction score/VAS score and the blood Eos percentage can be combined to differentiate Eos CRSwNP from non-Eos CRSwNP in a Chinese population.

Blood eosinophils and C-reactive protein as prognostic factors in severe chronic obstructive pulmonary disease exacerbations

BackgroundChronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Exacerbations of COPD are heterogeneous and have significant effect on the socioeconomic burden. The value of eosinophils (Eos) in predicting response to corticosteroids is documented in bronchial asthma exacerbation, but this value is not clear in COPD exacerbation. The aim of the study is to assess the prognostic value of blood Eos and C-reactive protein (CRP) in severe COPD exacerbations.Patients and methodsA total of 120 patients with COPD with severe exacerbations were subjected to complete blood count picture analysis with differential count, including Eos and CRP. Cases were divided into eosinophilic and nonesinophilic groups using 2% as a threshold, and the outcomes were observed.ResultsThe inpatient mortality rate was 10%, and it significantly correlated with noneosinophilic group (≤2%) (P=0.02). The length of stay in hospital and ICU was significantly lower in patients with eosinophilia more than or equal to 2%, with P value less than 0.001 for both. CRP and length of stay in hospital and ICU showed significant positive correlation.ConclusionHigher blood Eos and lower CRP levels can be used as predictors for better outcome in severe COPD exacerbations.

Age does not affect the efficacy of anti-IL-5/IL-5R in severe asthmatics

BackgroundHealthcare decisions made on the basis of insufficient evidence may potentially have ineffective or even harmful consequences. The proportion of older ages (over 65 years) in randomized controlled trials (RCTs) for severe asthma is not enough to establish whether anti-IL-5/IL-5R therapies are equally effective in the elderly as in younger subjects. MethodsIn order to assess the relationship between age and the efficacy of anti-IL-5 monoclonal antibodies (mABs) with respect to the risk of exacerbations and changes in FEV1, a meta-regression analysis via random-effect method was carried out by plotting the effect estimates (outcome variables) resulting from the pairwise meta-analysis with the age of asthmatic subjects (explanatory variable). A comprehensive literature search was performed for pivotal RCTs on the effects of anti-IL-5/IL-5R in severe asthma, with the following keywords: “asthma and mepolizumab”, “asthma and reslizumab” and “asthma and benralizumab”. The study was restricted to “clinical trials”, “age over 65” and “humans”. Data were checked for age, exacerbation rates, changes from baseline in FEV1, and blood eosinophil (Eos) count. Secondary outcomes included inhaled and oral medication use, clinical scores and quality of life. ResultsA total of 10 studies were analysed. Age did not modulate the efficacy of anti-IL-5/IL-5R treatment against the risk of exacerbation neither in the overall population (coefficient −0.007, P = 0.89), nor in patients with high blood Eos count (coefficient 0.075, P = 0.30). The blood Eos level drove the efficacy of anti-IL-5/IL-5R mABs against the risk of exacerbation regardless of age (coefficient −0.27, P < 0.001). Age did not significantly affect the efficacy of anti-IL-5/IL-5R mABs with respect to the change in FEV1 (coefficient −7.15, P = 0.190); however, in high Eos subjects this improvement tended to be less evident in the more advanced age ranges (coefficient −15.18, P = 0.087). In addition, anti-IL-5/IL-5R mABs reduced ACQ score (P < 0.001 vs. placebo), SGRQ score (P < 0.001 vs. placebo), Total Asthma Symptom Score (P < 0.05 vs. placebo), and the use of oral glucocorticoids (P < 0.001 vs. placebo). ConclusionsAge does not negatively affect the efficacy of anti-IL-5/IL-5R mABs. These findings support the use of anti-IL-5/IL-5R mABs in asthmatics of different age ranges.

Refractory asthma phenotyping based on immunoglobulin E levels and eosinophilic counts: A real life study.

Asthma is an inflammatory heterogeneous disease with variable severity. The serum IgE level and Eosinophilic count have been used as biomarkers to define treatment strategies with biological agents in severe refractory asthma. The aim of this study is to determine the concurrence of high eosinophil count and elevated serum IgE levels in patients with severe refractory asthma. A retrospective cross-sectional real-life study was conducted on patients attending adult refractory asthma outpatient clinic between 2015 and 2018. Serum total IgE level and blood EOS count on matched dates with spirometry and Asthma Control Test (ACT) scores were collected. All data were obtained while patients were not on biological agents. A total of 142 patients with severe refractory asthma were included. The mean age was 43 years, mean eosinophilic count 564 cells/μL and mean serum IgE levels of 520 IU/ml. There was a significant correlation between serum IgE level and eosinophilic count. Serum IgE and eosinophilic count were concurrently elevated in 110 patients (78%). The patients were further categorized into four subgroups. Group A: IgE 30-100 IU/mL and EOS 150-300 cells/μL (7.3%), Group B: IgE >100 IU/mL and EOS 150-300 cells/μL (19.1%), Group C: IgE 30-100 IU/mL and EOS >300 cells/μL (14.5%) and Group D: IgE >100 IU/mL, EOS >300 cells/μL (59.1%). The majority of severe refractory asthma patients exhibits both elevated serum IgE level and eosinophilic counts.

The clinical significance of diagnosis and therapy in patients with adult bronchial asthma by fractional exhaled nitric oxide levels

Objective To evaluate the sensitivity and specificity of exhaled nitric oxide in the diagnosis and therapy of bronchial asthma. Methods From January 2016 to December 2017, 87 patients diagnosed with bronchial asthma in Luoyang Central Hospital Affiliated to Zhengzhou University were selected as asthma group , and 40 healthy people were selected as healthy control group at the same term.The levels of FeNO, FEV1/pred, peripheral blood EOS count, ACT score, percentage of sputum EOS were measured. Results The positive rate of FeNO was 56.3%(49/87) in the asthma group, which in the healthy control group was 5.0%(2/47). The fractional exhaled nitric oxide level of reexamined patients before treatment [(70.9±53.6)ppb] was higher than that after treatment[(12.2±8.7)ppb], and the difference was statistically significant(t=4.323, P=0.001). The fractional exhaled nitric oxide level in the asthma group [(42.4±42.5)ppb] was higher than that in the healthy control group [(9.4±5.8)ppb], and the difference between the two groups was statistically significant(t=2.871, P=0.001). The fractional exhaled nitric oxide level was positively correlated with peripheral blood EOS count (r=0.376, P=0.000) and ACT score (r=0.361, P=0.001), but had no correlation with FEV1/pred (r=-0.111, P=0.306) and sputum EOS (r=-0.036, P=0.805). Conclusion The measurement of fractional exhaled nitric oxide levels has an important clinical significance in the diagnosis of bronchial asthma.And it has a guiding significance for the evaluation of the therapeutic effect of bronchial asthma. Key words: Asthma; Nitric oxide; Respiratory function tests; Oxyphil cells; Granulocytes; Glucocorticoids; Adult