Blood eosinophil count as a biomarker for therapy guidance in COPD and asthma exacerbations.

How Viral Infections Cause Exacerbation of Airway Diseases

BackgroundRecent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been...

BackgroundExacerbations of asthma and COPD are critical events. Eosinophilic inflammation is a treatable trait commonly found during acute exacerbations of asthma and COPD. We hypothesised that for patients with eosinophilic...

ObjectivesThis study aimed to evaluate the prevalence and clinical significance of elevated peripheral blood eosinophil (PBE) counts in hospitalised patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Oman. An elevated PBE count during AECOPD is a potential predictor of treatment responsiveness and future exacerbation risk.MethodsThis single-centre retrospective study included all patients with AECOPD who were admitted to Sultan Qaboos University Hospital, Muscat, Oman, between January 2017 and July 2019. The patients were classified as having eosinophilic or non-eosinophilic AECOPD based on blood eosinophil counts. An elevated eosinophil count was defined as a blood eosinophil count >0.3 × 109 cells/L on admission. The length of hospital stay, use of oral and inhaled steroids, number of readmissions in a year and use of mechanical ventilation on admission were compared between the eosinophilic and non-eosinophilic AECOPD groups.ResultsOf the 102 patients included in the study, 42.2% had eosinophilic AECOPD. The eosinophilic AECOPD group had a reduced length of hospital stay (P = 0.02) but an increased risk of readmission in a year (P = 0.04). Most patients in both groups were treated with inhaled and oral steroids. The need for mechanical ventilation did not differ between the groups.ConclusionEosinophilia is highly prevalent in patients with AECOPD and is associated with a reduced length of hospital stay but an increased risk of readmission in a year. It can be used as a surrogate marker to predict the health outcomes of patients with AECOPD and select treatment options.

Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated with the risk of asthma exacerbations among individuals with asthma from the general population. From the Copenhagen General Population Study with 81351 participants, we included 4838 with self-reported asthma. We recorded baseline blood eosinophil and neutrophil counts, and asthma exacerbations during follow-up in 2003-2011, defined as moderate (short-course treatment of prednisolone) or severe (hospitalization). The multivariable-adjusted incidence rate ratios (IRRs) were 1.28 (95% CI, 1.06-1.55) for moderate exacerbations and 1.55 (1.20-2.00) for severe exacerbations for individuals with blood eosinophil counts >0.29 × 109/L (highest tertile) vs individuals with blood eosinophil counts <0.18 × 109/L (lowest tertile). For blood neutrophils, the multivariable-adjusted IRRs were 2.14 (1.74-2.63) for moderate exacerbations and 1.18 (0.89-1.55) for severe exacerbations for individuals with blood neutrophil counts >4.85 × 109/L (highest tertile) vs individuals with blood neutrophil counts <3.77 × 109/L (lowest tertile). Blood eosinophil and neutrophil counts interacted on moderate exacerbations (P = 3 × 10-4), but not on severe exacerbations. High blood eosinophil counts are associated with an increased risk of both moderate and severe asthma exacerbations, while high blood neutrophil counts are associated with an increased risk of moderate, but not severe exacerbations.

Blood eosinophil counts and exacerbation risk in stable COPD with ≤1 moderate exacerbation on dual bronchodilator therapy.

Relationship of Blood Eosinophil Count to Exacerbations in Chronic Obstructive Pulmonary Disease

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the plasma fibrinogen level is associated with a decline in lung function and exacerbation of COPD. High blood eosinophil count is also associated with exacerbation of COPD in some studies but not others.OBJECTIVE: To investigate the associations between clinical phenotypes and plasma fibrinogen levels and blood eosinophil counts in patients with COPD.METHODS: Outpatients with COPD, in whom plasma fibrinogen level and blood eosinophil count were measured at least once simultaneously, were analysed retrospectively. Patients were classified into four groups, based on plasma fibrinogen level (threshold, 350 mg/dl) and blood eosinophil percentage (threshold, 2%). Clinical characteristics, comorbidities, laboratory data, COPD severity and exacerbations were compared in the four groups.RESULTS: Of 370 patients with COPD, the group with both high fibrinogen levels and eosinophil counts had more severe airflow limitation, more comorbidities and higher COPD severity indexes than the groups with low plasma fibrinogen. The annual rates of severe (0.29/year) and total (0.42/year) exacerbations were significantly higher in patients with both high fibrinogen and eosinophils than in the other three groups.CONCLUSION: Plasma fibrinogen levels and blood eosinophil counts may predict the clinical phenotype and frequency of exacerbations of COPD.

Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are important events and are associated with critical illness. Eosinophilic inflammation is a treatable trait commonly found during acute exacerbations of asthma and COPD. We hypothesised that for patients with eosinophilic exacerbations, a single injection of benralizumab, a humanised monoclonal antibody against interleukin-5 receptor-α, alone or in combination with prednisolone, will improve clinical outcomes compared with prednisolone, the standard of care. The Acute exacerbations treated with BenRAlizumab trial (ABRA) was a multicentre, phase 2, double-blind, double-dummy, active placebo-controlled randomised trial completed in the UK at Oxford University Hospitals NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust. Patients were recruited from urgent care clinics and emergency departments of these two hospitals. At the time of an acute exacerbation of asthma or COPD, adults with blood eosinophil counts of equal to or more than 300 cells per μL were randomly assigned in a 1:1:1 ratio to receive acute treatment with: prednisolone 30 mg once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA plus PRED group); placebo tablets once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA group); or prednisolone 30 mg once daily for 5 days and placebo subcutaneous injection once (PRED group). Randomisation was performed with a centralised interactive computer randomisation service. All patients and study research staff involved in data collection were masked to study blood results and treatment allocation. The co-primary outcomes were proportion of treatment failures over 90 days and total visual analogue scale (VAS) symptoms at day 28 in the pooled benralizumab groups compared with the prednisolone alone group and analysed in the intention-to-treat population. The trial was registered on Clinicaltrials.govNCT04098718. Between May 13, 2021, and Feb 5, 2024, 287 patients were screened for study inclusion. 129 were excluded due to not having an exacerbation captured or not meeting the eosinophil exclusion criteria. 158 patients were randomly assigned at acute eosinophilic exacerbation of asthma or COPD where 86 (54%) patients were female and 72 (46%) were male with a mean age of 57 years (range, 18-84). 53 patients were randomly assigned to the PRED group, 53 were randomly assigned to the BENRA group, and 52 were assigned to the BENRA plus PRED treatment group. At 90 days, treatment failures occurred in 39 (74%) of 53 in the PRED group, and 47 (45%) of 105 in the pooled-BENRA group (OR 0·26 [95% CI 0·13-0·56]; p=0·0005). The 28-day total VAS mean difference was 49 mm (95% CI 14-84; p=0·0065), favouring the pooled-BENRA group. There were no fatal adverse events and benralizumab was well tolerated. Notably, hyperglycaemia and sinusitis or sinus infection adverse events were related to the prednisolone study drug only. Benralizumab can be used as a treatment of acute eosinophilic exacerbations and achieves better outcomes than the current standard of care with prednisolone alone. These results offer a new way of treating eosinophilic endotypes of asthma and COPD exacerbations. AstraZeneca.

Management of Asthma and COPD Exacerbations in Adults in the ICU

Soluble triggering receptor expressed on myeloid cells-1 in acute respiratory infections

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a major cause of hospitalization and mortality worldwide. While blood eosinophils have been suggested as a prognostic biomarker of COPD, their predictive value in AECOPD remains uncertain. This meta-analysis aims to evaluate the prognostic role of blood eosinophil counts in predicting mortality and hospital readmission in these patients. A systematic review and meta-analysis were conducted according to PRISMA guidelines. We included studies that evaluated the prognostic role of blood eosinophils in AECOPD, with predefined cut-offs. Data on mortality and readmission rates were extracted, and statistical analyses were performed to assess sensitivity, specificity, and likelihood ratios. A total of 14 studies with 23,625 patients were included. High blood eosinophil counts during AECOPD hospitalization had low sensitivity (28.1%) and specificity (66.2%) in predicting 12-month mortality and readmission. Positive and negative likelihood ratios were also suboptimal, with values of 0.8 and 1.1, respectively. Sensitivity analyses, including only high-quality studies, confirmed these findings. The results suggest that blood eosinophil counts have limited prognostic value in predicting mortality and readmission in AECOPD patients. The variability in eosinophil cut-offs and lack of consistent data across studies contribute to this limitation. Further large-scale prospective studies are needed to clarify the role of eosinophils as a prognostic marker in AECOPD. Consequently, routine measurement of blood eosinophils during acute exacerbations may not be warranted for prognostic purposes.

Backgrounds The exacerbations of asthma and chronic obstructive pulmonary disease (COPD) have been suggested to be associated with respiratory tract viral infections (RTVIs). However, the rates of virus detection in previous studies have been quite variable, with lower rates for the exacerbation of COPD. Therefore, the virus detection of patients with exacerbation of asthma and COPD were investigated. Methods 20 and 24 patients with exacerbation of asthma and COPD, respectively, were enrolled. Nasal and sputum samples were taken, and polymerase chain reaction (PCR) for rhinovirus and coronavirus and virus culture for influenza A, B, RSV and parainfluenza virus performed. Results The mean FEV1/FVC in the exacerbation of asthma and COPD patients were 1.9/2.9 L (65.5%) and 1.1/2.6 L (42.3%), respectively. Respiratory virus was detected in 13 (65%) patients with exacerbation of asthma and rhinovirus was detected in 9. Coronavirus, influenza A, RSV and parainfluenza virus were detected in 2, 2, 1 and 1 patients with asthma. Among patients with exacerbation of COPD, a virus was detected in 14 (58.3%) patients, with rhinovirus, coronavirus and influenza A detected in 10, 3 and 4, respectively. Conclusions This study suggested that RTVIs may have a role in the exacerbation of COPD as well as asthma.

Background: There are currently limited real-world data on the clinical burden of illness in patients with COPD who continue to exacerbate despite receiving triple therapy. The aim of this study was to compare the burden of COPD in patients with and without a phenotype characterized by a high blood eosinophil count and high risk of exacerbations while receiving triple therapy.Methods: This retrospective cohort study (GSK ID: 207323/PRJ2647) used UK Clinical Practice Research Datalink records linked with Hospital Episode Statistics. Eligible patients had a COPD medical diagnosis code recorded between January 1, 2004 and December 31, 2014, and a blood eosinophil count recorded on/after that date. Patients were followed from index date (first qualifying blood eosinophil count) until December 31, 2015. The study phenotype was defined as ≥2 moderate/≥1 severe acute exacerbation of COPD (AECOPD) in the year prior to the index date, current use of multiple-inhaler triple therapy (MITT), and blood eosinophil count ≥150 cells/µL on the index date. Outcomes measured during follow-up included moderate/severe AECOPDs, severe AECOPDs, all-cause mortality, primary care (GP) clinical consultations, and non-AECOPD-related unscheduled hospitalizations.Results: Of 46,814 patients eligible for inclusion, 2512 (5.4%) met the definition of the study phenotype. Adjusted rate ratios (95% CI) of moderate/severe AECOPDs and all-cause mortality in patients with the study phenotype versus those without were 2.32 (2.22, 2.43) and 1.26 (1.16, 1.37), respectively. For GP visits and non-AECOPD-related unscheduled hospitalizations, adjusted rate ratios (95% CI), in patients with the study phenotype versus those without, were 1.09 (1.05, 1.12) and 1.31 (1.18, 1.46), respectively.Conclusion: Patients with COPD and raised blood eosinophil counts who continue to exacerbate despite MITT represent a distinct subgroup who experience substantial clinical burden and account for high healthcare expenditure. There is a need for more effective management and therapeutic options for these patients.

Differences in the spectrum of respiratory viruses and detection of human rhinovirus C in exacerbations of adult asthma and chronic obstructive pulmonary disease.