Lower Blood Eosinophil Counts Research Articles

High Blood Eosinophil Count at Stable State is Not Associated with Airway Microbiota Distinct Profile in COPD.

The heterogeneity of clinical features in COPD at stable state has been associated with airway microbiota. Blood eosinophil count (BEC) represents a biomarker for a pejorative evolution of COPD, including exacerbations and accelerated FEV1 decline. We aimed to analyse the associations between BEC and airway microbiota in COPD at stable state. Adult COPD patients at stable state (RINNOPARI cohort) were included and characterised for clinical, functional, biological and morphological features. BEC at inclusion defined 2 groups of patients with low BEC <300/mm3 and high BEC ≥300/mm3. Sputa were collected and an extended microbiological culture was performed for the identification of viable airway microbiota. Fifty-nine subjects were included. When compared with the low BEC (n=40, 67.8%), the high BEC group (n=19, 32.2%) had more frequent exacerbations (p<0.001) and more pronounced cough and sputum (p<0.05). The global composition, the number of bacteria per sample and the α-diversity of the microbiota did not differ between groups, as well as the predominant phyla (Firmicutes), or the gender repartition. In our study, high BEC in COPD at stable state was associated with a clinical phenotype including frequent exacerbation, but no distinct profile of viable airway microbiota compared with low BEC.

Severe asthma care trajectories: the French RAMSES cohort.

The French RAMSES study is an observational prospective multicentre real-life cohort including severe asthmatic subjects. The objective of the study was to compare the characteristics of patients, in terms of phenotype and asthma care trajectories, between those managed by tertiary referral centres (TRCs) or secondary care centres (SCCs). Patients were prospectively recruited and enrolled for a 5-year follow-up. Patients' characteristics were analysed at inclusion and compared between TRCs and SCCs. 52 centres (24 TRCs and 28 SCCs) included 2046 patients: 1502 (73.4%) were included by a TRC and 544 (26.6%) by a SCC. Patients were mainly women (62%), 53±15 years old, 67% with Asthma Control Test <20; at inclusion, 14% received oral corticosteroids (OCS) and 66% biologics. Compared with the SCC group, the TRC group had more frequent comorbidities and lower blood eosinophil counts (262 versus 340 mm-3; p=0.0036). OCS and biologics use did not differ between groups, but patients in the TRC group benefited more frequently from an educational programme (26% versus 18%; p=0.0008) and received more frequently two or more sequential lines of biologics (33% versus 24%; p=0.0105). In-depth investigations were more frequently performed in the TRC group (allergy tests: 74% versus 62%; p<0.0001; exhaled nitric oxide fraction: 56% versus 21%; p<0.0001; induced sputum: 6% versus 3%; p=0.0390). Phenotypes and care trajectories differed in the RAMSES cohort between SCCs and TRCs, probably related to different levels of asthma severity and differences in medical resources and practices among centres. This highlights the need for standardisation of severe asthma care.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6months of treatment. More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1month, 39% exhibited improvement at 6months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6months of treatment (OR and 95% CI 1.75 [1.09-2.98]). Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

Exhaled nitric oxide, eosinophils and current smoking in COPD patients.

High FENO can occur despite low blood eosinophil counts in ex-smokers, while a minority of current smokers have elevated FENO that is not related to eosinophil counts. FENO levels may be related to noneosinophilic mechanisms in a subgroup of COPD. https://bit.ly/3PSWvM2.

The Effect of Inhaled Corticosteroids on Pneumonia Risk in Patients With COPD-Bronchiectasis Overlap: A UK Population-Based Case-Control Study

Inhaled corticosteroids (ICS) increase the risk of pneumonia in COPD and commonly are used in patients with COPD-bronchiectasis overlap. Is the risk of pneumonia associated with ICS further heightened in COPD-bronchiectasis? Electronic health care records (from 2004-2019) were used to obtain a cohort of patients with COPD and a nested case-control group (age and sex matched 1:4). Analyses were conducted to determine the risk of hospitalization for pneumonia in COPD associated with ICS use in those with bronchiectasis. Findings were confirmed by several sensitivity analyses. Additionally, a smaller nested case-control group containing only patients with COPD-bronchiectasis overlap and those with recent blood eosinophil counts (BECs) was used to determine any association with BEC. Three hundred sixteen thousand six hundred sixty-three patients were eligible for the COPD cohort; bronchiectasis significantly increased the risk of pneumonia (adjusted hazard ratio, 1.24; 95%CI, 1.15-1.33). In the first nested case-control group of 84,316 patients with COPD, ICS was found to increase the odds of pneumonia (adjusted OR [AOR], 1.26; 95%CI, 1.19-1.32) only if used in the previous 180days. However, bronchiectasis was a significant modifier such that ICS use did not augment further the already elevated bronchiectasis-associated pneumonia risk (COPD-bronchiectasis: AOR, 1.01; 95%CI, 0.8-1.28; no bronchiectasis: AOR, 1.27; 95%CI, 1.20-1.34). Several sensitivity analyses and a second smaller nested case-control group confirmed these findings. Finally, we found that BEC modified the ICS-associated pneumonia risk in COPD-bronchiectasis overlap, where lower BEC was associated significantly with pneumonia (BEC≤ 3× 109/L: AOR, 1.56; 95%CI, 1.05-2.31; BEC > 3× 109/L: AOR, 0.89; 95%CI, 0.53-1.24). ICS use does not augment further the already increased risk of hospitalization for pneumonia associated with concomitant bronchiectasis in patients with COPD.

Clinical Implications of Longitudinal Blood Eosinophil Counts in Patients With Severe Asthma

The stability and variability of blood eosinophil counts (BECs) to phenotype patients with severe asthma is not fully understood. This post hoc, longitudinal, pooled analysis of placebo-arm patients from 2 phase 3 studies evaluated the clinical implications of BEC stability and variability in moderate-to-severe asthma. This analysis included patients from SIROCCO and CALIMA who received maintenance medium- to high-dosage inhaled corticosteroids plus long-acting β2-agonists; 2:1 patients with BECs of 300 cells/μL or higher and less than 300 cells/μL were enrolled. The BECs were measured 6 times over 1 year in a centralized laboratory. Exacerbations, lung function, and Asthma Control Questionnaire 6 scores were documented across patients grouped by BEC (<300 cells/μL or ≥300 cells/μL) and variability (<80% or ≥80% BECs less than or greater than 300 cells/μL). Among 718 patients, 42.2% (n= 303) had predominantly high, 30.9% (n= 222) had predominantly low, and 26.9% (n= 193) had variable BECs. Prospective exacerbation rates (mean ± SD) were significantly greater in patients with predominantly high (1.39 ± 2.20) and variable (1.41 ± 2.09) BECs versus predominantly low (1.05 ± 1.66) BECs. Similar results were observed for the number of exacerbations while on placebo. Although patients with variable BECs had intermittently high and low BECs, they experienced similar exacerbation rates to the predominantly high group, which were greater than those in the predominantly low group. A high BEC supports an eosinophilic phenotype in clinical settings without additional measurements, whereas a low BEC requires repeated measurements because it could reflect intermittently high or predominantly low BECs.

Simultaneous evaluation of the fractional exhaled nitric oxide and blood eosinophil count of T2-high endotype in patients with non-cystic fibrosis bronchiectasis.

Recently, a type 2 inflammation (T2) high endotype in bronchiectasis was identified. The fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) are recognized as representative biomarkers of T2 inflammation. Herein, we investigate the clinical characteristics of T2-high endotype in non-cystic fibrosis bronchiectasis patients classified by FeNO and BEC. This retrospective study included 164 bronchiectasis patients treated in the First Affiliated Hospital of Sun Yat-sen University from December 2017 to July 2022. Clinical characteristics were analyzed after classifying patients into four groups according to T2 inflammation biomarkers (FeNO ≥25ppb; BEC ≥200/µL). Among the 164 bronchiectasis patients, 35.3% (58/164) presented with high FeNO, 30.5% (50/164) presented with high BEC, and 10.4% (17/164) had high FeNO and BEC. Patients with high FeNO and low BEC presented with better lung function, fewer affected lobes, and lower dyspnea prevalence compared with the three other groups. Moreover, decreased FeNO, instead of decreased BEC, is revealed to be an independent predictor for disease severity and airflow obstruction in bronchiectasis. Simultaneous evaluation of FeNO and BEC proposed different endotypes of bronchiectasis established that patients with low BEC and high FeNO had better lung function, fewer affected lobes, lower dyspnea prevalence, and less disease severity. This result will contribute to a more comprehensive assessment of the disease severity and lead to more precise treatment of T2 inflammation in bronchiectasis patients.

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.

Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts< 100 cells/μL (BEC≤100) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC≤100 phenotype is inadequately characterized, especially in advanced COPD. Are there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes? We used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC≤100 vsBEC > 100 (BEC100+) in all subjects with COPD (n= 1,414) and GOLD group D subjects (n= 185) not receiving ICS. We identified n= 485 with BEC≤100 (n= 61 GOLD group D) and n= 929 people with BEC100+ (n= 124 GOLD group D). BEC≤100 status was stable at 6weeks and approximately 52weeks (intraclass correlations of 0.78 and 0.71, respectively). Compared with BEC100+, BEC≤100 comprised more women, with greater current smoking, and less frequent childhood asthma. Among all analyzed participants, the two BEC-defined subsets showed similar rates of lung function decline (mean slope, BEC≤100 vsBEC100+, -50 vs-39mL/y; P= .140), exacerbations (0.40 vs0.36/y; P= .098), subsequent ICS initiation (2.5%vs4.4%; P= .071), and mortality (7.8%vs8.4%; P= .715). However, in GOLD group D, people with BEC≤100 showed higher exacerbation rates within 365days of enrollment (0.62 vs0.33/y; P= .002) and total follow-up (1.16 vs0.83/y; P= .014). They also had greater lung function decline (mean slope of -68mL/y vs-23mL/y; P= .036) and had greater emphysema at baseline (voxels< 950 Hounsfield units at total lung capacity of 7.46%vs4.61%; P= .029). In non-ICS-treated GOLD group D COPD, people with BEC≤100 had more baseline emphysema, prospective exacerbations, and lung function decline. Our analysis has identified a particularly vulnerable subpopulation of people with COPD, suggesting the need for studies focused specifically on their therapeutic treatment. ClinicalTrials.gov; No.: NCT01969344; URL: www. gov.

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA AND HIGH BASELINE BLOOD EOSINOPHIL COUNTS

<h3>Introduction</h3> The efficacy of biologics for severe asthma is greater in patients with higher blood eosinophil counts (BECs) than those with lower BECs. Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced the annualized asthma exacerbation rate (AAER) in patients with severe, uncontrolled asthma, irrespective of baseline BECs. This exploratory analysis assessed the efficacy of tezepelumab in patients with high baseline BECs (≥ 500 cells/μL) in NAVIGATOR. <h3>Methods</h3> NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. At week 52, AAER and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV₁) were assessed by baseline BEC (≥ 500, ≥ 750 and ≥ 1000 cells/μL). <h3>Results</h3> Of 1059 patients, 209 had BECs ≥ 500 cells/μL, 76 had BECs ≥ 750 cells/μL and 33 had BECs ≥ 1000 cells/μL at baseline. Among placebo recipients, AAERs increased with increasing BEC. Tezepelumab reduced the AAER versus placebo by 74–77% across these BEC subgroups (<b>Figure</b>). Tezepelumab improved pre-BD FEV₁: least squares mean differences versus placebo were 0.26 L (95% confidence interval [CI]: 0.15–0.37), 0.21 L (95% CI: 0.02–0.40) and 0.41 L (95% CI: 0.13–0.69) in patients with baseline BECs ≥ 500, ≥ 750 and ≥ 1000 cells/μL, respectively. <h3>Conclusion</h3> Tezepelumab substantially reduced exacerbations and improved lung function versus placebo in patients with severe, uncontrolled asthma across all subgroups with high baseline BECs.

Identification of COPD Inflammatory Endotypes Using Repeated Sputum Eosinophil Counts.

Higher blood and sputum eosinophil counts are associated with a greater response to corticosteroids in COPD. Low blood eosinophil counts exhibit greater stability over time whereas higher counts demonstrate more variability. Stability of airway eosinophil levels is less well understood. We have studied the stability of sputum eosinophil counts. Differential cell count data for COPD patients (n = 100) were analysed. Subjects with two sputum eosinophil counts, 6 months apart, were included in the analysis. Patients were stratified based on baseline sputum eosinophil count into ‘low’, ‘intermediate’ and ‘high’ groups: eosinophilLOW (<1%), eosinophilINT (1–3%) and eosinophilHIGH (≥3%). Sputum eosinophil counts showed good stability (rho = 0.61, p < 0.0001, ICC of 0.77), with 67.4% of eosinophilLOW patients remaining in the same category on repeat sampling. Bland–Altman analysis of the whole cohort (median difference between measurements = 0.00%, 90th percentile = −1.4 and 4.7%) showed greater variation at higher counts. This was confirmed by the wider 90th centiles in the eosinophilINT (−1.50 to 5.65) and eosinophilHIGH groups (−5.33 to 9.80) compared to the eosinophilLOW group (−0.40 to 1.40). The repeatability of sputum eosinophil counts was related to the baseline eosinophil count; sputum eosinophilLOW COPD patients were relatively stable over time, while the eosinophilHIGH group showed greater variability. These results can facilitate the identification of COPD endotypes with differential responses to treatment.

Managing chronic obstructive pulmonary disease in primary care: clinical characteristics of patients receiving inhaled corticosteroids

AbstractBackgroundInhaled corticosteroid (ICS) therapy in patients with chronic obstructive pulmonary disease (COPD) has been associated with a variety of unfavourable effects, including increased risk of pneumonia, and is only recommended if specific characteristics are present to ensure patients derive the most benefit.AimThe primary objective was to evaluate the clinical characteristics of patients prescribed ICS therapy for COPD management in two primary care clinics at an academic medical centre. The secondary objectives were to examine provider assessment and barriers to prescribing patterns concordant with guidelines in the ambulatory care setting.MethodA retrospective 24‐month study at two primary care clinics was undertaken at an academic medical centre in Arkansas, United States and focused on adult patients who were prescribed ICS maintenance therapy. Individuals within each clinic were identified by Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) codes indicative of COPD from 1 January 2019 to 31 December 2020. Spirometry was also required to confirm diagnosis.ResultsOf the 189 unique patients identified, 100 were eligible for review of clinical characteristics. All patients received ICS therapy in combination with a long‐acting beta agonist (LABA) with 55% of patients also receiving a long‐acting muscarinic antagonist (LAMA). Furthermore, 32% of patients visited the emergency department or were hospitalised for a COPD exacerbation within the previous year. Approximately 47% and 36% of patients had a history of pneumonia and an eosinophil count &lt;100 cells/mcL respectively. Barriers to guideline adherence were identified through open discussion with providers within each clinic, which included a lack of readily available resources in the clinic setting, suboptimal recognition of clinical tools within the electronic medical record and alternative guideline preferences.ConclusionA small portion of patients evaluated in the study were discovered to have clinical characteristics suggestive of strong ICS benefit as these therapies either lacked efficacy due to low blood eosinophil count or exacerbation rate (80% and 68% respectively), or increased the risk for harm in this population secondary to previous pneumonia diagnosis (47%).

PASSAGE: A PHASE 4, SINGLE-ARM, OPEN-LABEL STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF TEZEPELUMAB IN PATIENTS WITH SEVERE ASTHMA, INCLUDING UNDER-REPRESENTED GROUPS

PASSAGE: A PHASE 4, SINGLE-ARM, OPEN-LABEL STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF TEZEPELUMAB IN PATIENTS WITH SEVERE ASTHMA, INCLUDING UNDER-REPRESENTED GROUPS

Clinical and economic burden of uncontrolled severe noneosinophilic asthma.

To quantify the clinical and economic burden of patients with severe asthma with low blood eosinophil counts (BECs) untreated with biologics. Retrospective cohort study in IBM MarketScan claims database. Patients 12 years and older with severe asthma with BEC data were selected between January 1, 2013, and June 30, 2018 (date of the most recent BEC was used as the index date). Inclusion criteria were (1) presence of BEC laboratory test result, (2) continuous enrollment for 12 months preceding and following the index date, (3) meeting the Healthcare Effectiveness Data and Information Set definition of persistent asthma, (4) meeting the Global Initiative for Asthma definition of severe asthma, and (5) an absence of biologic treatment, other respiratory diagnoses, and malignancies 12 months preceding and following the index date. Asthma exacerbations, levels of disease control, and all-cause and asthma-related health care costs were reported during the 12-month postindex period for patients with a BEC less than 300 cells/mcL. The sample included 8073 patients with severe asthma; 78% (n = 6260) presented with a BEC less than 300 cells/mcL. Mean (SD) age of the sample was 54.8 (14.2) years; 64% were female. Eighteen percent of patients had an asthma exacerbation; 19% had either uncontrolled or suboptimally controlled asthma based on the frequency of asthma-related hospital admissions, emergency department visits, or corticosteroid prescription fills. One-year all-cause and asthma-related total health care costs were $25,845 and $2802, respectively. Patients with suboptimally controlled and uncontrolled asthma spent $1471 and $3872 more, respectively, on asthma-related claims compared with patients with controlled asthma. Among patients with severe asthma with low eosinophils untreated with biologics, there is a high burden of disease among those who have suboptimal disease control, highlighting an unmet need in severe asthma treatment.

Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts.

Background: Combining a fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (B-EOS) may be a useful strategy for administration of biologics such as anti-IgE or anti-IL-5 to patients with type 2 inflammatory-predominant severe asthma and is important to be elucidated considering the increasing use of biologics. Methods: This cross-sectional study analyzed the clinical data from 114 adult patients with severe asthma, who were treated at Saitama Medical University Hospital. The eligible patients were stratified into four subgroups defined by thresholds of FeNO and blood eosinophil (B-EOS) counts to detect sputum eosinophilia, using the receiver operating characteristic curve analysis. A total of 75 patients with optimal samples were stratified into four subtypes defined by thresholds of sputum eosinophilia and neutrophilia. Clinical characteristics, pattern of biologics, and distribution of sputum subtypes were analyzed in the stratified subclasses according to the FeNO and B-EOS thresholds. The asthma exacerbation (AE)-free time of the FeNO/B-EOS subgroups and any biologics treatment including anti-IgE or anti-IL-5 use were examined using the Kaplan–Meier method. The hazard ratios (HRs) for AE-free time were examined using the Cox proportional hazard model. Results: The optimal cutoff values for prediction of sputum eosinophilia were defined as ≥2.7% wherein for FeNO as ≥27 ppb and B-EOS as ≥265/µL were considered. The high-FeNO subgroups showed significant high total IgE, compared with the low FeNO. The high-FeNO/high-B-EOS and the high-FeNO/low-B-EOS subgroups showed the largest prevalence of mepolizumab and benralizumab use among the other FeNO/B-EOS, respectively. The high-FeNO/low-B-EOS showed the largest frequency of AEs, high HR, and the shortest AE-free time, among the other FeNO/B-EOS. The sputum eosinophil-predominant subtype was the great majority in the high FeNO/high B-EOS. A diverse distribution of sputum leukocyte-predominant subtype was observed in the other FeNO/B-EOS. The subsequent AE-free time and its HR were comparable among the biologics use groups. Conclusion: The strategy of classifying severe asthma based on the combination of FeNO and B-EOS proposes particular refractory type 2 severe asthma and underlying airway inflammation as a feasible trait for optimal biologics use.

Phenotype of Asthma-COPD Overlap in COPD and Severe Asthma Cohorts.

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are airway diseases with similar clinical manifestations, despite differences in pathophysiology. Asthma-COPD overlap (ACO) is a condition characterized by overlapping clinical features of both diseases. There have been few reports regarding the prevalence of ACO in COPD and severe asthma cohorts. ACO is heterogeneous; patients can be classified on the basis of phenotype differences. This study was performed to analyze the prevalence of ACO in COPD and severe asthma cohorts. In addition, this study compared baseline characteristics among ACO patients according to phenotype.MethodsPatients with COPD were prospectively enrolled into the Korean COPD subgroup study (KOCOSS) cohort. Patients with severe asthma were prospectively enrolled into the Korean Severe Asthma Registry (KoSAR). ACO was defined in accordance with the updated Spanish criteria. In the COPD cohort, ACO was defined as bronchodilator response (BDR) ≥ 15% and ≥ 400 mL from baseline or blood eosinophil count (BEC) ≥ 300 cells/μL. In the severe asthma cohort, ACO was defined as age ≥ 35 years, smoking ≥ 10 pack-years, and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity < 0.7. Patients with ACO were divided into four groups according to smoking history (threshold: 20 pack-years) and BEC (threshold: 300 cells/μL).ResultsThe prevalence of ACO significantly differed between the COPD and severe asthma cohorts (19.8% [365/1,839] vs. 12.5% [104/832], respectively; P < 0.001). The percentage of patients in each group was as follows: group A (light smoker with high BEC) – 9.1%; group B (light smoker with low BEC) – 3.7%; group C (moderate to heavy smoker with high BEC) – 73.8%; and group D (moderate to heavy smoker with low BEC) – 13.4%. Moderate to heavy smoker with high BEC group was oldest, and showed weak BDR response. Age, sex, BDR, comorbidities, and medications significantly differed among the four groups.ConclusionThe prevalence of ACO differed between COPD and severe asthma cohorts. ACO patients can be classified into four phenotype groups, such that each phenotype exhibits distinct characteristics.

Low Peripheral Blood Eosinophil Counts in Patients with Acute Graft-Versus-Host-Disease Prior to Systemic Corticosteroid Therapy Is Associated with Poor Prognosis

Background: Acute graft-versus-host-disease (aGVHD) is one of the main complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), occurring in about half of patients. Patients with grade II-IV aGVHD require treatment with systemic corticosteroids. However, 30% of them show steroid resistance, leading to poor prognosis. Thus, pretreatment prediction of steroid refractoriness allows for early secondary treatment introduction, which may improve aGVHD outcomes. The possible association between elevated peripheral blood (PB) eosinophil counts and the development of aGVHD has been previously reported. In contrast, several studies showed an association with better outcomes after allo-HSCT. These reports imply that PB eosinophil counts may predict prognosis in patients with aGVHD. In this study, we investigated the predictive role of pretreatment PB eosinophil counts in patients with aGVHD treated with systemic corticosteroid therapy.Methods: Retrospective case analysis was performed on 121 patients with hematological malignancies who underwent allo-HSCT between October 2010 and January 2017 in our institutes and developed any grade of aGVHD. We excluded patients who did not require systemic corticosteroid therapy (n=53), and who developed aGVHD after premature discontinuation of calcineurin inhibitors (n=5) because of relapse or calcineurin toxicities. Finally, a total of 63 patients were enrolled. PB smears obtained within 2 days before the start of systemic corticosteroid therapy were microscopically examined. The cut-off value of eosinophil counts for predicting survival was determined using receiver operating characteristic (ROC) curve analysis. The primary endpoint was 1-year overall survival (OS), measured from the start of systemic corticosteroid therapy to death due to any cause or the last follow-up. The secondary endpoints were 1-year progression-free survival (PFS), 1-year cumulative incidence (CI) of non-relapse mortality (NRM), and CI of relapse. OS and PFS were compared using the log-rank test and CIs of NRM and relapse were compared using Gray's test. Predictors of OS were evaluated using univariate and multivariate analysis using Cox's proportional hazards model.Results: The median age was 48 years (range: 40-59 years), and 31 patients (60.8%) were male. Primary diagnoses were acute myeloid leukemia (n=21), acute lymphoblastic leukemia (n=18), myelodysplastic syndrome (n=9), malignant lymphoma (n=13), multiple myeloma (n=1), and chronic myelomonocytic leukemia (n=1). They received bone marrow (n=38), peripheral blood stem cells (n=5), and cord blood (n=20). The median PB eosinophil count was 96/mm3 (range: 0-2903/mm3). ROC analysis revealed the cut-off value for predicting 1-year OS as 133/mm3 (area under the curve: 0.783; 95% confidence interval, 0.662-0.904). Thus, we defined patients with eosinophil counts ≥133/mm3 as the “high eosinophil group” (n=30) and the others as the “low eosinophil group” (n=33). There was no difference in clinical characteristics between the two groups, with the exception of days from transplantation to systemic corticosteroid therapy (29 days in the low eosinophil group vs. 43 days in the high eosinophil group, p<0.001). Regarding the primary endpoint, the 1-year OS rates were 65.2% and 93.3% in the low and high eosinophil groups, respectively (p=0.008) (Figure A). In the univariate analysis, the hazard ratio (HR) for 1-year OS of the low eosinophil group was 6.0 (95% confidence interval: 1.3-27.2, p=0.020). In the multivariate analysis adjusted for eosinophil counts (low vs. high), recipient age (≥50 vs. <50 years), aGVHD grade (III-IV vs. I-II), and stem cell source, the low eosinophil group showed independent poor prognosis for 1-year OS (HR, 6.0; 95% confidence interval, 1.3-28.4; p=0.023). Especially in patients with grade III-IV aGVHD, the low eosinophil group showed substantially inferior 1-year OS rates than those in the high eosinophil group (35.0% vs. 88.9%, p=0.032) (Figure B). Regarding secondary endpoints, 1-year PFS rates were 59.2% and 89.9% (p=0.006), 1-year CI rates of NRM were 21.7% and 3.33% (p=0.035), and 1-year CI rates of relapse were 19.1% and 6.8% (p=0.145) in the low and high eosinophil groups, respectively (Figures C-E).Conclusion: Low PB eosinophil counts before systemic corticosteroid therapy is associated with inferior 1-year OS after aGVHD due to elevated NRM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Blood tryptase and thymic stromal lymphopoietin levels predict the risk of exacerbation in severe asthma

Some patients with severe asthma experience exacerbations despite receiving multiple therapy. The risk of exacerbation and heterogeneous response to treatment may be associated with specific inflammatory molecules that are responsive or resistant to corticosteroids. We aimed to identify the independent factors predictive for the future risk of exacerbation in patients with severe asthma. In this multi-center prospective observational study, 132 patients with severe asthma were enrolled and divided into exacerbation (n = 52) and non-exacerbation (n = 80) groups on the basis of exacerbation rate after a 1-year follow-up period. We found that previous history of severe-to-serious exacerbation, baseline blood eosinophil counts (≥ 291cells/μL), and serum tryptase (≤ 1448 pg/mL) and thrymic stromal lymphopoietin (TSLP) levels (≥ 25 pg/mL) independently predicted the future development of exacerbation with adjusted odds ratios (AOR) of 3.27, 6.04, 2.53 and 8.67, respectively. Notably, the patients with high blood eosinophil counts and low tryptase levels were likely to have more exacerbations than those with low blood eosinophil counts and high tryptase levels (AOR 16.9). TSLP potentially played the pathogenic role across different asthma phenotypes. TSLP and tryptase levels may be implicated in steroid resistance and responsiveness in the asthma inflammatory process. High blood eosinophil counts and low serum tryptase levels predict a high probability of future asthma exacerbation.

COVID-19-Induced Anosmia and Ageusia Are Associated With Younger Age and Lower Blood Eosinophil Counts.

Anosmia and ageusia are symptoms commonly associated with COVID-19, but the relationship with disease severity, onset and recovery are unclear. To examine factors associated with anosmia and ageusia and the recovery from these symptoms in an ethnically diverse cohort. Individuals tested for SARS-CoV-2 between March and April 2020 were eligible for the study. Randomly selected participants answered a telephone questionnaire on COVID-19 symptoms with a focus on anosmia and ageusia. Additionally, relevant past medical history and data on the COVID-19 clinical course were obtained from electronic medical records. 486 patients were in the COVID-19 group and 103 were COVID-19-negative. Patients who were younger were more likely to report anosmia and/or ageusia (odds ratio (OR) for anosmia per 1-year increase in age: 0·98, 95%CI:0-97-0·99, p = 0·003; for ageusia: 0·98, 95%CI:0·97-0·99, p = 0·005) as were patients with lower eosinophil counts (OR for anosmia per 0.1-K/μL increase in eosinophils: 0·02, 95%CI:0·001-0·46, p = 0·01, for ageusia 0·10, 95%CI:0·01-0·97, p = 0·047). Male gender was independently associated with a lower probability of ageusia (OR:0·56, 95%CI:0·38-0·82, p = 0·003) and earlier sense of taste recovery (HR:1·44, 95%CI:1·05-1·98, p = 0·02). Latinos showed earlier sense of taste recovery than white patients (HR:1·82, 95%CI:1·05-3·18, p = 0·03). Anosmia and ageusia were more common among younger patients and those with lower blood eosinophil counts. Ageusia was less commonly reported among men, and time to taste recovery was earlier among both men and Latinos.

Prognostic impact of eosinophils in peripheral blood and tumor site in patients with esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy

To date, no effective biological markers have been identified for predicting the prognosis of esophageal cancer patients. Recent studies have shown that eosinophils are independent prognostic factors in some cancers. This study aimed to identify the prognostic impact of eosinophils in esophageal squamous cell carcinoma patients treated with concurrent chemoradiotherapy (CCRT).This study enrolled 136 patients who received CCRT for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). We evaluated the survival time and clinical pathological characteristics of eosinophils. The Kaplan–Meier method was used to estimate survival data. The log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used to conduct a multivariate analysis.Kaplan–Meier analysis revealed that high eosinophil infiltration correlated with better overall survival (OS) (P = .008) and better progression-free survival (PFS) (P = .015). The increase in absolute eosinophil count after CCRT also enhanced OS (P = .005) and PFS (P = .007). The PFS and OS in patients with high blood eosinophil count before CCRT (>2%) was better than those with low blood eosinophil count(<2%) (P = .006 and P = .001, respectively). Additionally, the multivariate analysis revealed that disease stage and high eosinophil infiltration, increased peripheral blood absolute eosinophil count after CCRT, and high peripheral blood eosinophil count before CCRT were independent prognostic indicators.High eosinophil count of tumor site, increased peripheral blood absolute eosinophil count after CCRT, and high peripheral blood eosinophil count before CCRT are favorable prognostic factors for patients with ESCC treated with CCRT.