High Blood Eosinophil Counts Research Articles

Peripheral blood eosinophilia in adult asthmatic patients and its association with the severity of asthma

BackgroundAsthma is a diverse disease with various etiologic bases. Severe asthma can be associated with increased mortality, hospitalization, and decreased quality of life for asthma patients. High blood eosinophil counts were associated with severe asthma, but recent studies have failed to confirm this as a marker of severe asthma among adult asthma patients. As a result, the purpose of this study was to determine the association between the severity of asthma and high blood eosinophil count.MethodologyA simple random sampling technique was used to select 291 asthmatic patients for an institution-based cross-sectional study. Socio-demographic, behavioral, and clinical characteristics were collected by using a pre-tested structured questionnaire. Four milliliters of venous blood were collected from asthmatic patients for complete blood count and peripheral morphology assessment. The eosinophil count was analyzed by the Unicel DxH 800 (Beckman Coulter, Ireland) analyzer. A statistical package for social science version 20 (SPSS) software was used to analyze the data. The non-parametric (Mann-Whitney U) test was used to compare the eosinophil count with different background variables. A binary logistic regression analysis was used to assess the factors associated with eosinophilia. A p-value less than 0.05 in multivariable logistic regression analysis was considered statistically significant.ResultIn this study, the overall magnitude of eosinophilia was 19.6% (95% CI = 14.8–24.1). Being admitted to the emergency department (AOR = 0.25; 95% CI: 0.09–0.69, p = 0.007) and being female (AOR = 0.49; 95% CI: 0.26–0.9, p = 0.025) were shown to have a statistically significant association with eosinophilia. Moreover, the absolute eosinophil count was significantly higher among asthmatic patients infected with intestinal parasitic infection (p < 0.045).ConclusionBeing female and admission to the emergency department were negatively associated with eosinophilia. Lack of eosinophilia can be related to the low-T2 asthma phenotype. The absolute eosinophil counts were higher among intestinal parasite-infected patients. Therefore, different biomarkers will be considered for the proper diagnosis and management of adult asthma patients.

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.

Sputum Type 2 Markers Could Predict Remission in Severe Asthma Treated With Anti-IL-5

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments. Even if high blood eosinophil counts seem to be associated with a reduction in exacerbations with treatment targeting IL-5, we lack biomarkers for the prediction of remission after these very expensive treatments. Are there biomarkers of remission after therapy targeting IL-5 in the sputum of patients with severe eosinophilic asthma? This observational study included 52 patients with severe asthma initiated with anti-IL-5 therapy and recruited from the asthma clinic of the Centre Hospitalier Universitaire of Liege, Belgium. Remission was defined as patients who combined the following at 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire score< 1.5, asthma control test score > 19, or both; FEV1 of≥ 80%predicted, improvement of FEV1 of≥ 10%, or both; and a blood eosinophil count< 300 cells/μL. Eosinophil peroxidase (EPX), IgE, IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor, thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels were measured in the sputum of these patients before anti-IL-5 treatment. Among the 52 patients, 11 were classified as being in remission. These patients were characterized by higher sputum eosinophil, macrophage, and lymphocyte counts, whereas the sputum neutrophil percentage was lower than in the nonremission group. In addition, the sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein levels were higher at baseline in the remission group compared with the nonremission group. Univariate regression analysis revealed that male vsfemale sex, sputum neutrophil percentage, eotaxin-1, IL-5, and EPX were potential predictors of remission. Sputum type 2 markers seemed to be potentially predictive of remission after anti-IL-5 therapy in a cohort of patients with severe eosinophilic asthma. These results need validation on a larger cohort.

Stepwise management of COPD: What is next after bronchodilation?

Inhaled bronchodilator therapy with long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) in combination is currently the mainstay of treatment for chronic obstructive pulmonary disease (COPD). Treatment guidelines recommend the addition of inhaled corticosteroids (ICS) to LABA/LAMA only in patients with a history of frequent/severe exacerbations and high blood eosinophil counts, or in those with concomitant asthma. Despite this, real-world data suggest that clinicians are not adhering to this guidance and that ICS are frequently overused. This is possibly due to the incorrect assumption that when LABA/LAMA therapy is not sufficient, adding an ICS to the treatment regimen is the logical next step. In this narrative review, we describe global and country-specific guideline recommendations from Germany, Spain, and Japan and compare these with real-world data on LABA/LAMA and ICS use in clinical practice. We also provide a clinical guide to the use of add-on therapies with LABA/LAMA for different patient phenotypes, including (1) patients still symptomatic (but not exacerbating) despite LABA/LAMA treatment; (2) patients still exacerbating despite LABA/LAMA treatment who have high blood eosinophil counts; and (3) patients still exacerbating despite LABA/LAMA treatment who do not have high blood eosinophils or concomitant asthma.

Real-World Investigation of Eosinophilic-Associated Disease Overlap (REVEAL): Analysis of a US Claims Database.

The epidemiology of eosinophil-associated diseases (EADs) is not yet fully understood. While some studies have been conducted on stand-alone eosinophilic diseases, there is scarce evidence on the degree of overlap among rarer conditions. The retrospective Real-world inVestigation of Eosinophilic-Associated disease overLap (REVEAL) study used data from the Optum® Clinformatics® insurance claims database to describe and characterize disease overlap among 11 EADs: allergic bronchopulmonary aspergillosis, atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic gastritis/gastroenteritis, eosinophilic granulomatosis with polyangiitis, eosinophilic esophagitis, bullous pemphigoid, chronic obstructive pulmonary disorder, chronic spontaneous urticaria, and non-cystic fibrosis bronchiectasis. Patient records with EADs of interest were identified between January 1, 2015, and June 30, 2018. Overall, 1,326,645 patients were included; 74.4% had 1 EAD, 20.5% had ≥ 2 EADs, and 5.1% had ≥ 3 EADs. Higher rates of disease overlap were associated with older age. Higher blood eosinophil counts were also observed in patients with a greater number of overlapping conditions, suggesting a common role for eosinophilic inflammation in the pathogenesis of multiple diseases. Furthermore, greater disease overlap was associated with higher disease severity in most cohorts. Results from this study have implications for quantifying unmet needs and can be used to inform treatment guidelines and raise the awareness of eosinophilic inflammation and EAD overlap among healthcare professionals from a range of disease specialties.

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.

Clinically important deterioration: a composite tool for managing patients with COPD

Clinically important deterioration (CID) is a composite tool developed to measure COPD's progression. It is a promising concept that can improve treatment choices for COPD patients because it provides a more holistic assessment of their status in everyday clinical practice. The post hoc analysis of several trials that were important for improving COPD treatment provides increasing evidence of the importance of assessing CID. These retrospective evaluations suggest that dual bronchodilation should be preferred over a single bronchodilator if treatment aims to reduce a possible clinical deterioration of COPD. Should dual bronchodilation prove ineffective, evidence shows that triple therapy, including an inhaled corticosteroid, is effective in preventing CID, especially in the presence of high blood eosinophil counts. CID initially included changes in FEV1 ≥100 mL from baseline, an increase in total SGRQ score ≥4 units, or a moderate/severe exacerbation. These thresholds were chosen arbitrarily because they were considered clinically relevant. Therefore, this multidimensional tool is being improved by including outcomes and thresholds that consider the peculiarities of the COPD population and the duration of the assessment. However, at present, studies that have assessed the impact of CID on COPD are almost all retrospective. Therefore, prospective studies need to be conducted that allow the complete validation of this instrument and better define the most effective components in assessing the risk of deterioration of COPD.

Evaluation of the Prevalence of Barotrauma and Affecting Factors in Patients with COVID-19 during Follow-Up in the Intermediate Care Unit.

It is known that pneumothorax (PX) and pneumomediastinum (PM) develop due to COVID-19 disease. The objective of our study was to determine the prevalence of PX/PM due to COVID-19 in the intermediate intensive care unit (IMCU) and to evaluate the factors causing barotrauma and also the clinical outcomes of these patients. A total of 283 non-intubated patients with COVID-19 pneumonia followed up in the IMCU in a 1-year period were included in the study. The patients were classified as group 1 (having barotrauma) and group 2 (without barotrauma). The rate of barotrauma was 8.1% (n = 23, group 1). PX developed on the right hemithorax in 12 (70.6%) patients. Group 1 had statistically significantly higher 28-day mortality rates compared with group 2 (p = 0.014). The eosinophil and d-dimer levels of the patients in group 1 were higher, while C-reactive protein (CRP), fibrinogen, and albumin levels were lower than Group 2 (p < 0.001, p = 0.017, p = 0.001, p < 0.001), and p < 0.001, respectively). The similar rates of NIMV administration in our study groups support that barotrauma is not the only mechanism in the development of PX/PM. The findings of high blood eosinophil count and low blood levels of CRP, albumin, and fibrinogen in the barotrauma group of our study might be a pathfinder for future studies.

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.

Blood Eosinophil Endotypes across Asthma and Chronic Obstructive Pulmonary Disease (COPD).

Background Eosinophils were common inflammatory cells involved in the occurrence and development of various inflammatory diseases. Multiple recent studies have pointed to the increasingly important role of eosinophils in respiratory diseases. This article aims to compare the expression differences of blood eosinophil counts between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Methods Patients with asthma, COPD, and ACO who were seen in the First Affiliated Hospital of Guangzhou Medical University from January 2012 to June 2019 were included. We collected information such as age, gender, diagnosis, the eosinophil counts from the medical records. Moreover, the levels of 10 cytokines in the plasma of each group were detected by using the Meso Scale Discovery method. Results We included 9787 patients with asthma, 15806 patients with COPD, and 831 ACO patients. From our results, it can be first found that eosinophil levels were age-related in the three diseases (asthma and ACO: p < 0.001; COPD: P = 0.001); in asthma and COPD, the number of eosinophils in males was more significant than that in females (asthma: p < 0.001; COPD: p = 0.012). Second, asthma patients had higher blood eosinophil counts than those with COPD and ACO (p < 0.001). Moreover, we found out that eosinophil levels were highly expressed in the stable group of all three diseases. Finally, we found that most cytokines in ACO patients showed a downward trend when the level of eosinophils was low, whereas the results were reversed in asthma patients; 7 cytokines had similar trends in COPD and ACO patients. Conclusions In conclusion, eosinophils have their own unique endotypes in asthma, COPD, and ACO patients, which were reflected in the fluctuation of their levels and changes in cytokine secretion.

White blood cell count and chronic obstructive pulmonary disease: A Mendelian Randomization study

Blood leukocyte counts (e.g., eosinophil count) are important biomarkers for the onset, classification, and exacerbation of chronic obstructive pulmonary disease (COPD). The causal relationships between them are necessary for the development of COPD treatment strategy, but remain unclear. Here, we implement two-sample bi-directional univariable Mendelian Randomization (MR) and multivariable MR to investigate the causal relationships. Univariable MR find that elevated blood eosinophil count significantly increases the risk of COPD (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14–1.30, P = 1.54 × 10−09) and COPD-related hospitalization (OR = 1.44, 95% CI: 1.15–1.80, P = 1.36 × 10−03). Besides, it also significantly decreases the ratio of forced expiratory volume in the first second over forced vital capacity (FEV1/FVC ratio) (OR = 0.942, 95% CI: 0.914–0.971, P = 1.02 × 10−04). These findings are fully supported by multivariate MR results. Interestingly, univariable MR reveals a weak causal relationship between elevated blood eosinophil count and COPD risk in younger people (<65 years) (OR = 1.39, 95% CI: 1.10–1.75, P = 5.52 × 10−03), but not older individuals (OR = 1.20, 95% CI: 0.926–1.55, P = 0.17). Finally, reverse univariable MR reveals the onset of COPD and the decreased FEV1/FVC ratio both lead to increased blood neutrophil count (OR = 1.03, 95% CI: 1.01–1.05, P = 3.40 × 10−03 and OR = 0.947, 95% CI: 0.91–0.986, P = 8.75 × 10−03 respectively). In summary, this MR study demonstrates that high blood eosinophil count is an independent causal mediator of COPD risk, FEV1/FVC decline, and COPD-related hospitalization. The increase in neutrophil count is induced by COPD onset or FEV1/FVC decline. This suggests eosinophil, but not neutrophil, may be used as a therapeutic target for preventing the onset and exacerbation of COPD and FEV1/FVC decline. Therefore, a non-neutrophil-targeted therapeutic strategy for neutrophilic COPD is required in the future.

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

Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy.

BackgroundMany severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics.MethodsBaseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson’s chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons.ResultsBetween January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147).ConclusionAround one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.

Artículo traducido] Asociación entre eosinófilos de sangre periférica y cutáneos con la gravedad del penfigoide ampolloso y los resultados terapéuticos

Background and aimsA dermal inflammatory infiltrate rich in eosinophils is a prominent histological feature of bullous pemphigoid (BP) and peripheral blood eosinophilia has been documented in 50–60% of BP patients. Nevertheless, the impact of circulating and dermal infiltrate eosinophil levels on BP remains poorly understood. The main objective of this work was to investigate the association of peripheral blood and dermal infiltrate eosinophil levels with clinical and immunological characteristics of the disease. Material and methodsRetrospective cohort study including all patients diagnosed with BP between 2011 and 2020. ResultsThe study cohort included 233 patients with BP. The mean baseline peripheral blood eosinophil count was 956.3 ± 408.6 × 106/L and the mean number of tissue eosinophils at the dermal hot spot area was 30.5 ± 19.0. Patients with disseminated presentation (i.e. BSA > 50%) had significantly higher peripheral blood eosinophil counts (P = .028). Mucosal involvement was significantly associated with lower dermal eosinophil count (P = .001). Requiring inpatient care and relapsing were significantly associated with high peripheral blood eosinophil count (P = .025; P = .020, respectively). Among the 68 patients who experienced a relapse, 31 had peripheral blood eosinophilia (i.e. > 500 × 106/L) at relapse (44.2%). Peripheral blood eosinophil counts at baseline and at relapse were significantly correlated (r = 0.82, P < .001). ConclusionsPeripheral blood and cutaneous eosinophils levels may be useful biomarkers for disease activity and treatment outcomes in BP. Monitoring peripheral blood eosinophil counts may allow early detection of relapse.

Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study

Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies on PAL in asthma have included relatively small populations, mostly restricted to severe asthma, or have no included longitudinal data. The aim of this post-hoc analysis was to investigate the determinants, clinical implications, and outcome of PAL in patients with asthma who were included in the ATLANTIS study. In this post-hoc analysis of the ATLANTIS study, we assessed the prevalence, clinical characteristics, and implications of PAL across the full range of asthma severity. The study population included patients aged 18-65 years who had been diagnosed with asthma at least 6 months before inclusion. We defined PAL as a post-bronchodilator FEV1/forced vital capacity (FVC) of less than the lower limit of normal at recruitment. Asthma severity was defined according to the Global Initiative for Asthma. We used Mann-Whitney U test, t test, or χ2 test to analyse differences in baseline characteristics between patients with and without PAL. Logistic regression was used for multivariable analysis of the associations between PAL and baseline data. Cox regression was used to analyse risk of exacerbation in relation to PAL, and a linear mixed-effects model was used to analyse change in FEV1 over time in patients with versus patients without PAL. Results were validated in the U-BIOPRED cohort. Between June 30, 2014 and March 3, 2017, 773 patients were enrolled in the ATLANTIS study of whom 760 (98%) had post-bronchodilator FEV1/FVC data available. Of the included patients with available data, mean age was 44 years (SD 13), 441 (58%) of 760 were women, 578 (76%) were never-smokers, and 248 (33%) had PAL. PAL was not only present in patients with severe asthma, but also in 21 (16%) of 133 patients with GINA step 1 and 24 (29%) of 83 patients with GINA step 2. PAL was independently associated with older age at baseline (46 years in PAL group vs 43 years in non-PAL group), longer duration of asthma (24 years vs 12 years), male sex (51% vs 38%), higher blood eosinophil counts (median 0·27 × 109 cells per L vs 0·20 × 109 cells per L), more small airway dysfunction, and more exacerbations during 1 year of follow-up. Associations between PAL, age, and eosinophilic inflammation were validated in the U-BIOPRED cohort, whereas associations with sex, duration of asthma, and risk of exacerbations were not validated. PAL is not only present in severe disease, but also in a considerable proportion of patients with milder disease. In patients with mild asthma, PAL is associated with eosinophilic inflammation and a higher risk of exacerbations. Our findings are important because they suggest that increasing treatment intensity should be considered in patients with milder asthma and PAL. Chiesi Farmaceutici and Dutch Ministry of Economic Affairs and Climate Policy (by means of the public-private partnership programme).

Association of Peripheral Blood and Cutaneous Eosinophils With Bullous Pemphigoid Disease Severity and Treatment Outcomes

Background and aimsA dermal inflammatory infiltrate rich in eosinophils is a prominent histological feature of bullous pemphigoid (BP) and peripheral blood eosinophilia has been documented in 50–60% of BP patients. Nevertheless, the impact of circulating and dermal infiltrate eosinophil levels on BP remains poorly understood. The main objective of this work was to investigate the association of peripheral blood and dermal infiltrate eosinophil levels with clinical and immunological characteristics of the disease. Material and methodsRetrospective cohort study including all patients diagnosed with BP between 2011 and 2020. ResultsThe study cohort included 233 patients with BP. The mean baseline peripheral blood eosinophil count was 956.3±408.6×106/L and the mean number of tissue eosinophils at the dermal hot spot area was 30.5±19.0. Patients with disseminated presentation (i.e. BSA>50%) had significantly higher peripheral blood eosinophil counts (P=0.028). Mucosal involvement was significantly associated with lower dermal eosinophil count (P=0.001). Requiring inpatient care and relapsing were significantly associated with high peripheral blood eosinophil count (P=0.025; P=0.020, respectively). Among the 68 patients who experienced a relapse, 31 had peripheral blood eosinophilia (i.e. >500×106/L) at relapse (44.2%). Peripheral blood eosinophil counts at baseline and at relapse were significantly correlated (r=0.82, P<0.001). ConclusionsPeripheral blood and cutaneous eosinophils levels may be useful biomarkers for disease activity and treatment outcomes in BP. Monitoring peripheral blood eosinophil counts may allow early detection of relapse.

Characteristics, phenotypes, mechanisms and management of severe asthma.

Severe asthma is “asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.” The state of control was defined by symptoms, exacerbations and the degree of airflow obstruction. Therefore, for the diagnosis of severe asthma, it is important to have evidence for a diagnosis of asthma with an assessment of its severity, followed by a review of comorbidities, risk factors, triggers and an assessment of whether treatment is commensurate with severity, whether the prescribed treatments have been adhered to and whether inhaled therapy has been properly administered. Phenotyping of severe asthma has been introduced with the definition of a severe eosinophilic asthma phenotype characterized by recurrent exacerbations despite being on high dose ICS and sometimes oral corticosteroids, with a high blood eosinophil count and a raised level of nitric oxide in exhaled breath. This phenotype has been associated with a Type-2 (T2) inflammatory profile with expression of interleukin (IL)-4, IL-5, and IL-13. Molecular phenotyping has also revealed non-T2 inflammatory phenotypes such as Type-1 or Type-17 driven phenotypes. Antibody treatments targeted at the T2 targets such as anti-IL5, anti-IL5Rα, and anti-IL4Rα antibodies are now available for treating severe eosinophilic asthma, in addition to anti-immunoglobulin E antibody for severe allergic asthma. No targeted treatments are currently available for non-T2 inflammatory phenotypes. Long-term azithromycin and bronchial thermoplasty may be considered. The future lies with molecular phenotyping of the airway inflammatory process to refine asthma endotypes for precision medicine.

Clinical Characteristics of Patients and Factors Associated with Switching Biologics in Asthma.

PurposeBiologics have been used increasingly for the treatment of severe asthma. However, established guidelines for the selection, switching, or discontinuation of biologics do not exist. We aimed to identify the clinical characteristics of patients with asthma who required switching biologics and the factors associated with switching biologics.Patients and MethodsThis was a retrospective study of 42 patients with severe asthma treated with biologics at the Hokkaido University Hospital between 23rd June 2016 and 30th April 2021, when two biologics were available in Japan. We compared the characteristics of subjects who continued and switched biologics. The time to switch the biologics was assessed by type 2 inflammatory biomarkers, pulmonary function indices, and the presence of comorbidities, including the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score and aspirin exacerbated respiratory diseases (AERD), using the Kaplan–Meier method and a multivariate Cox proportional hazards model.ResultsEight and five patients were treated by mepolizumab and benralizumab at baseline, respectively among the 31% (13/42) who switched the biologics. Subjects who required switching biologics were characterized by high blood eosinophil counts, younger age, JESREC scores of 11 points or higher, and AERD. The time taken to switch biologics was significantly shorter in the subgroups with high JESREC scores (≥11) or AERD, compared with their counterparts with low JESREC scores or without AERD (both, P < 0.05). JESREC scores of ≥11, but not the presence of AERD, were associated with time to switch biologics.ConclusionThe presence of eosinophilic chronic rhinosinusitis based on JESREC scores of ≥11 and younger age were factors associated with switching biologics in asthma.

Methylxanthine Treatment in Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease in China: A Real-World Study Using Propensity Score Matching Analysis.

Background: Although medical guidelines discourage the use of methylxanthines in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), they are still widely used in clinical practice. This study investigated the real-world use of methylxanthines in the management of AECOPD. Methods: Patient data from the Acute exacerbation of Chronic obstructive pulmonary disease Using REgistry data (ACURE, NCT02657525) study database were screened. Enrolled patients were divided into treatment and control groups. Propensity score (PS) matching and Cox regression analyses were used to minimize confounding factors and determine the association between methylxanthine treatment and the length of stay (LOS). Results: Among the 2088 eligible patients, 1,563 (74.9%) were in the methylxanthine treatment group. Patients treated with methylxanthines had more severe respiratory symptoms and worse lung function than those in the control group. Doxophylline was the most commonly used methylxanthine in both secondary and tertiary hospitals. After PS matching, 966 patients were equally divided into two groups. The LOS of patients in the two groups was similar [median: 8 days, interquartile range (IQR): 7–11 days, p = 0.730]. Patients in the treatment group (median: 8, IQR: 4–12) had a more significant decrease in the COPD Assessment Test score from admission to discharge than those in the control group (median: 6, IQR: 2–10, p < 0.001). Among all matched patients, the LOS was not significantly associated with methylxanthine treatment [adjusted hazard ratio (HR): 1.02, 95% confidence intervals (CIs): 0.89–1.16]. However, in the subgroup analysis, methylxanthines were significantly associated with a short LOS in patients with blood eosinophil count >4% (adjusted HR: 1.56, 95% CIs: 1.12–2.17). Conclusion: This study revealed that methylxanthines, especially doxophylline, are widely used in China. Methylxanthines were effective in improving symptoms in AECOPD patients. Higher blood eosinophil count may be associated with a better efficacy of methylxanthine treatment.

Preoperative Sinonasal Computed Tomography Score in Chronic Rhinosinusitis with Nasal Polyps.

This study investigated the relationship between sinonasal inflammatory involvement according to the computed tomography (CT) staging system (Lund–Mackay score) with clinical, laboratory, histopathological and prognostic features of chronic rhinosinusitis with nasal polyps (CRSwNP). Seventy-eight patients with CRSwNP who had undergone surgery were enrolled. Total (p = 0.0062), ethmoid (p = 0.0496), sphenoid (p = 0.0335), ostiomeatal complex (OMC) (p = 0.0235) and frontal (p = 0.0164) CT scores were predictive of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD) in the univariate analysis. Total (p = 0.0022), ethmoid (p = 0.0290), sphenoid (p = 0.0370), frontal (p = 0.0116), maxillary (p = 0.0357) and OMC (p = 0.0058) CT scores were predictve of asthma at the univariate analysis. No significant differences were found between patients with vs. without allergy in terms of total and partial CT scores. High blood eosinophil counts (>0.24 vs. ≤0.24 cells × 109/L) resulted in being associated with total (p = 0.0213), maxillary (p = 0.0227) and ethmoid (p = 0.0491) CT scores in the univariate analysis. Higher ethmoid (p = 0.0006) and total sinonasal (p = 0.0027) CT scores were found to predict histopathologically eosinophil CRSwNPs in the univariate analysis. CT scores did not result as predictive of NSAID-exacerbated respiratory disease, asthma, or blood eosinophil count at the multivariate analysis. Risk of relapse was related to the presence of NERD (p = 0.0207, HR [95% CI] 3.914 [1.232–12.435]), higher preoperative total (HR = 1.098 95%CI: 1.001–1.204, p = 0.0486) and frontal sinus CT scores (HR = 1.555 95%CI: 1.006–1.886, p = 0.0218), but these results were not confirmed by the multivariable analysis. Sinonasal CT scores showed significant differences in this heterogeneous inflammatory condition. Identifying CRSwNP characteristics is necessary to avoid generic treatments with poor outcomes.