Blood Eosinophil Counts in Chronic Obstructive Pulmonary Disease: A Biomarker of Inhaled Corticosteroid Effects.
Singh Dave
Tuberculosis and respiratory diseases
Blood eosinophil counts have emerged as a chronic obstructive pulmonary disease (COPD) biomarker that predict the effects of inhaled corticosteroids (ICS) in clinical practice. Post-hoc and prospective analysis of randomized control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to ICS. COPD patients with frequent exacerbations (2 or more moderate exacerbations/yr) or a history of hospitalization have a greater response to ICS. Ex-smokers also appear to have a greater ICS response. Blood eosinophil counts can be combined with clinical information such as exacerbation history and smoking status to enable a precision medicine approach to the use of ICS. Higher blood eosinophil counts are associated with increased eosinophilic lung inflammation, and other biological features that may contribute to the increased ICS response observed. Emerging data indicates that lower blood eosinophil counts are associated with an increased risk of bacterial infection, suggesting complex relationships between eosinophils, ICS response, and the airway microbiome.
10.4046/trd.2020.0026
Chronic obstructive pulmonary disease.
Barnes Peter J,Burney Peter G J,Silverman Edwin K,Celli Bartolome R,Vestbo Jørgen,Wedzicha Jadwiga A,Wouters Emiel F M
Nature reviews. Disease primers
Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression.
10.1038/nrdp.2015.76
Peripheral Blood Eosinophil as a Biomarker in Outcomes of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
Wu Hong-Xia,Zhuo Kai-Quan,Cheng De-Yun
International journal of chronic obstructive pulmonary disease
Purpose:Mounting evidence suggests that eosinophil levels correlate with the effects of therapy and phenotype for chronic obstructive pulmonary disease (COPD). This study aimed to clarify the relationship between eosinophil levels and clinical outcomes in patients with acute exacerbation of COPD (AECOPD). Methods:A prospective, multicenter, observational cohort study was performed in three teaching hospitals. Patients were grouped by quartile percentage (0, 0.7, 2.55) and absolute blood eosinophils count (0, 0.05×10/L, 0.17×10/L) and divided into four numbered groups ranked from low to high. Results:The study included 493 AECOPD patients. In the percentile-ranked groups, patients in Group 1 experienced significantly longer hospital stays, higher rates of both noninvasive mechanical ventilation (NIMV), and heart failure than those in Group 4 (12 days vs 10 days, p = 0.005; 29.5% vs 23.6%, p = 0.007; 48.4% vs 28.5%, p = 0.001). Group 1 also had higher frequencies of respiratory failure and pulmonary heart disease compared to Groups 3 and 4 (54.8% vs 34.8%, p = 0.002; 54.8% vs 35%, p = 0.003). In the absolute count-ranked groups, patients in Group 1 had significantly higher rates of NIMV than those in Group 3 (41.1% vs 21.7%, p = 0.001), had higher rates of heart failure, respiratory failure, and pulmonary heart disease than those in Group 3 and 4 (48.1% vs 30.2%, p = 0.003; 48.1% vs 30.4%, p = 0.005; 50.8% vs 32.2%, p = 0.004; 50.8% vs 34.1%, p = 0.008; 51.9% vs 34.1%, p = 0.004; 51.9% vs 33%, p = 0.003). There were outcome differences among the admitting hospital of stays in the absolute count groups (p = 0.002), but the differences were not significant in a pairwise comparison. The proportion of ICU admissions and mortality was different in two cohorts with no difference in a pairwise comparison. Conclusion:Patients with lower eosinophil counts experienced poorer clinical outcomes. Eosinophil levels may be a helpful marker to predict outcomes in AECOPD.
10.2147/COPD.S226783
Eosinophils in COPD-Current Concepts and Clinical Implications.
Mycroft Katarzyna,Krenke Rafal,Górska Katarzyna
The journal of allergy and clinical immunology. In practice
In recent years, heterogeneity in chronic obstructive pulmonary disease (COPD) inflammatory patterns has been recognized as a basis for more precise treatment interventions because current therapies have limited effectiveness. Eosinophilic airway inflammation in COPD has become a subject of research interest as a potential treatment target for inhaled corticosteroid therapy. However, the role of eosinophils in COPD is still unclear, and it is unknown why only some patients with COPD develop eosinophilic airway inflammation. Induced sputum analysis is the most common method of assessing the type of airway inflammation. Accessibility to sputum induction, however, is limited in clinical practice, and blood eosinophils have been proposed to serve as a surrogate marker and treatment guide. Blood eosinophil count has been shown to poorly predict sputum eosinophilia, and, moreover, it seems to be fairly unstable and affected by various factors. Nevertheless, in several trials, blood eosinophil count appeared to predict good response to inhaled corticosteroids However, biologics targeting eosinophils do not appear to be effective in COPD. In this review, we briefly summarize the current knowledge on eosinophils in COPD pathogenesis. Then, we discuss the use of blood eosinophil count in COPD in relation to the recent Global Initiative for Chronic Obstructive Pulmonary Disease recommendations, their ability to predict sputum eosinophilia, and their potential role in guiding treatment.
10.1016/j.jaip.2020.03.017
A perspective for chronic obstructive pulmonary disease (COPD) management: six key clinical questions to improve disease treatment.
Contoli Marco,Morandi Luca,Di Marco Fabiano,Carone Mauro
Expert opinion on pharmacotherapy
INTRODUCTION:In 2011, the GOLD recommendations for the treatment of Chronic Obstructive Pulmonary Disease (COPD) introduced new clinical elements to classify the severity of the disease and to guide pharmacological choice. For the first time in the GOLD documents, treatment decision was no longer guided only by pulmonary function, but by a more complex combination of pulmonary function and clinical aspects. The recent versions of the GOLD recommendations introduce new aspects for the clinicians and pose new question for the management of the disease. In addition, inflammatory biomarkers and blood eosinophil levels, have been considered to guide treatment selection. AREA COVERED:The evolution of disease management proposed by the GOLD document opens several areas of debate. A series of roundtable discussions among respiratory physicians took place in Italy to address key clinical questions. Particularly, the role of lung function and the use of biomarkers, the adherence to international guidelines and the possibility to personalize the pharmacological approach in COPD patients have been discussed, summarized and analyzed. EXPERT OPINION:The authors believe that the development of a precision medicine approach tailoring the specific treatment for each patient is the goal of COPD management and may be achieved by considering the phenotypic classification of COPD patients.
10.1080/14656566.2020.1828352
The association between blood eosinophil percent and bacterial infection in acute exacerbation of chronic obstructive pulmonary disease.
Choi Juwhan,Oh Jee Youn,Lee Young Seok,Hur Gyu Young,Lee Sung Yong,Shim Jae Jeong,Kang Kyung Ho,Min Kyung Hoon
International journal of chronic obstructive pulmonary disease
The use of antibiotics is based on the clinician's experience and judgment, and antibiotics may often be overused in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Eosinophils have been studied as biomarkers of bacterial infection and prognostic factors in chronic obstructive pulmonary disease and AECOPD. Thus, the purpose of this study was to determine whether eosinophils could be used to determine bacterial infection in AECOPD events. We retrospectively analyzed the medical records of patients admitted to Korea University Guro Hospital for AECOPD between January 2011 and May 2017. Data pertaining to baseline characteristics, results of previous pulmonary function tests, treatment information during the admission period, and history of pulmonary treatment were collected before admission. A total of 736 AECOPD events were eligible for inclusion and were divided into two groups based on the eosinophil count: those involving eosinophil counts of less than 2% (546 events) and those involving counts of 2% or more (190 events). In univariate analysis, the only bacterial pathogen identification events and bacterial-viral pathogen co-identification events were significantly more frequent in the group with eosinophil counts of less than 2% (=0.010 and =0.001, respectively). In logistic regression analysis, the rates of only bacterial pathogen identification [odds ratios =1.744; 95% confidence interval, 1.107-2.749; =0.017] and bacterial-viral pathogen co-identification [odds ratios=2.075; 95% confidence interval, 1.081-3.984; =0.028] were higher in the group with eosinophil count less than 2%. In conclusion, eosinophil counts of less than 2% are potential indicators of a bacterial infection in AECOPD events. Eosinophils could thus serve as a reference for the use of antibiotics in AECOPD treatment.
10.2147/COPD.S197361
Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial.
Pascoe Steven,Barnes Neil,Brusselle Guy,Compton Chris,Criner Gerard J,Dransfield Mark T,Halpin David M G,Han MeiLan K,Hartley Benjamin,Lange Peter,Lettis Sally,Lipson David A,Lomas David A,Martinez Fernando J,Papi Alberto,Roche Nicolas,van der Valk Ralf J P,Wise Robert,Singh Dave
The Lancet. Respiratory medicine
BACKGROUND:Previous studies have highlighted a relationship between reduction in rate of exacerbations with therapies containing inhaled corticosteroids (ICS) and baseline blood eosinophil count in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial showed that once-daily single-inhaler triple therapy significantly reduced exacerbations versus dual therapies. Blood eosinophil counts and smoking status could be important modifiers of treatment response to ICS. We aimed to model these relationships and their interactions, including outcomes other than exacerbations. METHODS:IMPACT was a phase 3, randomised, double-blind, parallel-group, 52-week global study comparing once-daily single-inhaler triple therapy (fluticasone furoate-umeclidinium-vilanterol) with dual inhaled therapy (fluticasone furoate-vilanterol or umeclidinium-vilanterol). Eligible patients had moderate-to-very-severe COPD and at least one moderate or severe exacerbation in the previous year. We used fractional polynomials to model continuous blood eosinophil counts. We used negative binomial regression for numbers of moderate and severe exacerbations, severe exacerbations, and pneumonia. We modelled differences at week 52 in trough FEV, St George's Respiratory Questionnaire (SGRQ) total score, and Transition Dyspnoea Index using repeated measurements mixed effect models. IMPACT was registered with ClinicalTrials.gov, number NCT02164513. FINDINGS:The magnitude of benefit of regimens containing ICS (fluticasone furoate-umeclidinium-vilanterol n=4151 and fluticasone furoate-vilanterol n=4134) in reducing rates of moderate and severe exacerbations increased in proportion with blood eosinophil count, compared with a non-ICS dual long-acting bronchodilator (umeclidinium-vilanterol n=2070). The moderate and severe exacerbation rate ratio for triple therapy versus umeclidinium-vilanterol was 0·88 (95% CI 0·74 to 1·04) at blood eosinophil count less than 90 cells per μL and 0·56 (0·47 to 0·66) at counts of 310 cells per μL or more; the corresponding rate ratio for fluticasone furoate-vilanterol versus umeclidinium-vilanterol was 1·09 (0·91 to 1·29) and 0·56 (0·47 to 0·66), respectively. Similar results were observed for FEV, Transition Dyspnoea Index, and SGRQ total score; however, the relationship with FEV was less marked. At blood eosinophil counts less than 90 cells per μL and at counts of 310 cells per μL or more, the triple therapy versus umeclidinium-vilanterol treatment difference was 40 mL (95% CI 10 to 70) and 60 mL (20 to 100) for trough FEV, -0·01 (-0·68 to 0·66) and 0·30 (-0·37 to 0·97) for Transition Dyspnoea Index score, and -0·01 (-1·81 to 1·78) and -2·78 (-4·64 to -0·92) for SGRQ total score, respectively. Smoking status modified the relationship between observed efficacy and blood eosinophil count for moderate or severe exacerbations, Transition Dyspnoea Index, and FEV, with former smokers being more corticosteroid responsive at any eosinophil count than current smokers. INTERPRETATION:This analysis of the IMPACT trial shows that assessment of blood eosinophil count and smoking status has the potential to optimise ICS use in clinical practice in patients with COPD and a history of exacerbations. FUNDING:GlaxoSmithKline.
10.1016/S2213-2600(19)30190-0
Value of Exhaled Nitric Oxide (FeNO) And Eosinophilia During the Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Hospital Admission.
Río Ramírez Maria Teresa,Juretschke Moragues María Antonia,Fernández González Rocío,Álvarez Rodríguez Virginia,Aznar Andrés Elena,Zabaleta Camino Juan Pedro,Romero Pareja Rodolfo,Esteban de la Torre Andrés
COPD
The aim of this study was to analyze whether FeNO levels in acute exacerbation of COPD (AECOPD) with hospital admission have better diagnostic value than eosinophilia in blood, and to evaluate its usefulness in predicting a better clinical response. An observational prospective study of patients with AECOPD was carried out. FeNO determinations were made on arrival at the emergency room (ER), at discharge and during stability 3-6 months after discharge. Co-morbidities, bronchodilators, inhaled (IGC) and systemic (SGC) glucocorticoids, eosinophils, systemic inflammation markers (procalcitonin, C-reactive protein), eosinophil cationic protein, and total IgE were collected. Fifty consecutive patients (92% men, mean age 75 ± 6 years) were included in this study. Phenotypes were 26% Asthma-COPD Overlap Syndrome (ACOS), 42% chronic bronchitis (CB) and 32% emphysema. ACOS patients showed significantly higher levels of FeNO (73 ppb) and eosinophils (508 cells/mm) than the rest (CB: 23 ppb, 184 cells/mm, emphysema: 27 ppb, 159 cells/mm; p < 0.05). A significant correlation between FeNO levels measured in ER and eosinophils was observed (r = 0.7; p < 0.001), but not at discharge or in stable phase. No significant association was found with parameters of systemic inflammation and mean stay. In conclusion, the determination of FeNO in AECOPD does not offer advantages over the evaluation of eosinophilia. These parameters rise at arrival in ER, descend at discharge, and remain unchanged in the stable phase. Both present similar diagnostic utility and are able to better identify the ACOS phenotype, which helps select a population that could benefit from a glucocorticoids therapy.
10.1080/15412555.2018.1482532
Blood Eosinophils and Response to Maintenance Chronic Obstructive Pulmonary Disease Treatment. Data from the FLAME Trial.
Roche Nicolas,Chapman Kenneth R,Vogelmeier Claus F,Herth Felix J F,Thach Chau,Fogel Robert,Olsson Petter,Patalano Francesco,Banerji Donald,Wedzicha Jadwiga A
American journal of respiratory and critical care medicine
RATIONALE:Post hoc analyses suggest that blood eosinophils have potential as a predictive biomarker of inhaled corticosteroid efficacy in the management of chronic obstructive pulmonary disease (COPD). OBJECTIVES:We prospectively investigated the value of blood eosinophils as a predictor of responsiveness to an inhaled corticosteroid/long-acting β-agonist combination versus a long-acting β-agonist/long-acting muscarinic antagonist combination for exacerbation prevention. METHODS:We conducted prespecified analyses of data from the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone Salmeterol on COPD Exacerbations) study, which compared once-daily long-acting β-agonist/long-acting muscarinic antagonist indacaterol/glycopyrronium 110/50 μg with twice-daily long-acting β-agonist/inhaled corticosteroid salmeterol/fluticasone combination 50/500 μg in patients with one or more exacerbations in the preceding year. Subsequent post hoc analyses were conducted to address further cutoffs and endpoints. MEASUREMENTS AND MAIN RESULTS:We compared treatment efficacy according to blood eosinophil percentage (<2% and ≥2%, <3% and ≥3%, and <5% and ≥5%) and absolute blood eosinophil count (<150 cells/μl, 150 to <300 cells/μl, and ≥300 cells/μl). Indacaterol/glycopyrronium was significantly superior to salmeterol/fluticasone for the prevention of exacerbations (all severities, or moderate or severe) in the <2%, ≥2%, <3%, <5%, and <150 cells/μl subgroups, and at no cutoff was salmeterol/fluticasone superior to indacaterol/glycopyrronium. Furthermore, the rate of moderate or severe exacerbations did not increase with increasing blood eosinophils. The incidence of pneumonia was higher in patients receiving salmeterol/fluticasone than indacaterol/glycopyrronium in both the <2% and ≥2% subgroups. CONCLUSIONS:Our prospective analyses indicate that indacaterol/glycopyrronium provides superior or similar benefits over salmeterol/fluticasone regardless of blood eosinophil levels in patients with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).
10.1164/rccm.201701-0193OC
Relationship between Blood and Induced Sputum Eosinophils, Bronchial Hyperresponsiveness and Reversibility of Airway Obstruction in Mild-to-Moderate Chronic Obstructive Pulmonary Disease.
Proboszcz Malgorzata,Mycroft Katarzyna,Paplinska-Goryca Magdalena,Górska Katarzyna,Nejman-Gryz Patrycja,Jankowski Piotr,Zak Natalia,Krenke Rafal
COPD
Blood eosinophilia has been proposed as a surrogate marker for airway eosinophilia and as a predictor of treatment response in chronic obstructive pulmonary disease (COPD). The aim of the study was to assess the relationship between blood and sputum eosinophils and to investigate the association between blood and sputum eosinophil count and clinical features of mild-to-moderate COPD. We performed a retrospective analysis of blood and sputum eosinophil count, as well as demographic and lung function data in a cohort of 90 stable, steroid-naive (Global Initiative for Chronic Obstructive Lung Disease 1 or 2) COPD patients and 20 control subjects. Blood and sputum eosinophil count did not correlate both in patients with COPD ( = -0.04 = 0.705) and in controls ( = 0.05, = 0.838). Sputum eosinophilia (≥3%) was present in 40% of COPD patients. The median blood eosinophil count in patients with COPD was 180 (interquartile range 90-270)/μL; patients with low blood eosinophils (<180/μL) did not differ from those with high blood eosinophils (≥180/μL) in terms of forced expiratory volume in 1 second, bronchial reversibility or hyperresponsiveness. This was also the case when COPD patients with and without sputum eosinophilia were compared. At the same time, positive bronchial reversibility and positive bronchial hyperresponsiveness were observed in 2 (11%) COPD patients with high blood eosinophils and in 1 (5%) patient with sputum eosinophilia. There was a weak, albeit significant correlation ( = 0.22 = 0.041) between blood eosinophil count and age in patients with COPD. Peripheral eosinophil count poorly reflects sputum eosinophils and lung function in stable steroid-naive mild-to-moderate COPD patients.
10.1080/15412555.2019.1675150