scholarly journals Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort

2017 ◽  
Vol 50 (4) ◽  
pp. 1700853 ◽  
Author(s):  
Viktoriya L. Kim ◽  
Ngaire A. Coombs ◽  
Karl J. Staples ◽  
Kristoffer K. Ostridge ◽  
Nicholas P. Williams ◽  
...  

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) predicts response to treatment, especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations, and its associations with clinical phenotype, exacerbations and infection.127 patients aged 40–85 years with moderate to very severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for 1 year.Blood eosinophils ≥2% was prevalent at baseline, and predicted both predominantly raised stable-state eosinophils across the year (area under the curve 0.841, 95% CI 0.755–0.928) and increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001). Eosinophils ≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49; p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly eosinophilic patients.Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations, which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important condition.

2021 ◽  
Vol 8 (1) ◽  
pp. e000960
Author(s):  
Emanuel Citgez ◽  
Job van der Palen ◽  
Paul van der Valk ◽  
Huib A M Kerstjens ◽  
Marjolein Brusse-Keizer

BackgroundThe blood eosinophil count has been shown to be a promising biomarker for establishing personalised treatment strategies to reduce corticosteroid use, either inhaled or systemic, in chronic obstructive pulmonary disease (COPD). Eosinophil levels seem relatively stable over time in stable state, but little is known whether this is also true in subsequent severe acute exacerbations of COPD (AECOPD).Aims and objectivesTo determine the stability in eosinophil categorisation between two subsequent severe AECOPDs employing frequently used cut-off levels.MethodsDuring two subsequent severe AECOPDs, blood eosinophil counts were determined at admission to the hospital in 237 patients in the Cohort of Mortality and Inflammation in COPD Study. The following four cut-off levels were analysed: absolute counts of eosinophils ≥0.2×10⁹/L (200 cells/µL) and ≥0.3×10⁹/L (300 cells/µL) and relative eosinophil percentage of ≥2% and ≥3% of total leucocyte count. Categorisations were considered stable if during the second AECOPD their blood eosinophil status led to the same classification: eosinophilic or not.ResultsDepending on the used cut-off, the overall stability in eosinophil categorisation varied between 70% and 85% during two subsequent AECOPDs. From patients who were eosinophilic at the first AECOPD, 34%–45% remained eosinophilic at the subsequent AECOPD, while 9%–21% of patients being non-eosinophilic at the first AECOPD became eosinophilic at the subsequent AECOPD.ConclusionsThe eosinophil variability leads to category changes in subsequent AECOPDs, which limits the eosinophil categorisation stability. Therefore, measurement of eosinophils at each new exacerbation seems warranted.


2021 ◽  
Author(s):  
Ahmed Yousuf ◽  
Hamish McAuley ◽  
Omer Elneima ◽  
Christopher E Brightling

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. To improve the health status and reduce symptom burden, it is important to identify a group of patients with similar characteristics and prognosis, called clinical phenotypes. Herein we shall review the different phenotypes of COPD. Sources of data Keywords (COPD, phenotype, acute exacerbation) search was conducted in PubMed, Google Scholar. Areas of agreement Those with raised blood eosinophil counts respond better to steroid therapy at stable state and exacerbation. Areas of controversy There is no universally accepted blood eosinophil cut-off value that will indicate favourable response to corticosteroids and potentially for future biologic therapy. Growing points There is an urgent need for further therapeutic options for COPD patients with non-eosinophilic inflammation. Areas timely for developing research Well-designed COPD trials with identification of phenotypes for more personalization of the treatment of COPD.


2021 ◽  
Vol 12 ◽  
pp. 204062232110287
Author(s):  
Tao Liu ◽  
Zi-Jian Xiang ◽  
Xiao-Meng Hou ◽  
Jing-Jing Chai ◽  
Yan-Li Yang ◽  
...  

Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and dyspnea, as well as an increase in the number of leukocytes in the airways, lungs, and pulmonary vessels. A ‘One size fits all’ approach to COPD patients with different clinical features may be considered outdated. The following are the two major objectives of this meta-analysis: the first is to determine if blood eosinophil counts (BEC) can serve as a prognostic biomarker of COPD outcomes, and the second is to determine which level of BEC is effective for inhaled corticosteroid (ICS) treatment. Methods: We searched articles published before 15 May 2021 in the following four electronic databases: Web of Science, Cochrane Library, EMBASE, and PubMed. Results: A total of 42 studies, comprising a sampling of 188,710 subjects, were summarized and compared in this meta-analysis. The rate ratio (RR) of exacerbations of COPD (ECOPD) between ICS and non-ICS treatment was statistically significant for the COPD patients with a baseline BEC ⩾ 2% or ⩾ 200 cells/μl, RR = 0.82 (0.73, 0.93) or 0.79 (0.70, 0.89) respectively, while the RR of ECOPD between ICS and non-ICS treatment was statistically insignificant for the COPD patients with baseline BEC < 2% or <200 cells/μl, RR = 0.97 (0.87, 1.08) or 0.97 (0.86, 1.08), suggested that ICS therapy was beneficial to the improvement of ECOPD in patients with a baseline BEC ⩾ 2% or BEC ⩾ 200 cells/μl. Conclusion: Our research shows that a BEC ⩾ 200 cells/μl or ⩾2% is likely to become the cutoff value of ICS treatment for ECOPD. Moreover, we believe that the baseline BEC can be used as a biomarker for predicting ECOPD. The stability of BEC requires special attention.


2018 ◽  
Vol 6 (3) ◽  
pp. 74 ◽  
Author(s):  
James Camp ◽  
Jennifer Cane ◽  
Mona Bafadhel

In an era of precision medicine, it seems regressive that we do not use stratified approaches to direct treatment of oral corticosteroids during an exacerbation of chronic obstructive pulmonary disease (COPD). This is despite evidence suggesting that 40% of COPD patients have eosinophilic inflammation and this is an indicator of corticosteroid response. Treatments with oral corticosteroids are not always effective and not without harm, with significant and increased risk of hyperglycemia, sepsis, and fractures. Eosinophils are innate immune cells with an incompletely understood role in the pathology of airway disease. They are detected at increased levels in some patients and can be measured using non-invasive methods during states of exacerbation and stable periods. Despite the eosinophil having an unknown mechanism in COPD, it has been shown to be a marker of length of stay in severe hospitalized exacerbations, a predictor of risk of future exacerbation and exacerbation type. Although limited, promising data has come from one prospective clinical trial investigating the eosinophil as a biomarker to direct systemic corticosteroid treatment. This identified that there were statistically significant and clinically worsened symptoms in patients with low eosinophil levels who were prescribed prednisolone, demonstrating the potential utility of the eosinophil. In an era of precision medicine our patients’ needs are best served by accurate diagnosis, correct identification of maximal treatment response and the abolition of harm. The peripheral blood eosinophil count could be used towards reaching these aims.


2019 ◽  
Vol 54 (2) ◽  
pp. 1900651 ◽  
Author(s):  
Christopher Brightling ◽  
Neil Greening

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality worldwide, and its prevalence is increasing. Airway inflammation is a consistent feature of COPD and is implicated in the pathogenesis and progression of COPD, but anti-inflammatory therapy is not first-line treatment. The inflammation has many guises and phenotyping this heterogeneity has revealed different patterns. Neutrophil-associated COPD with activation of the inflammasome, T1 and T17 immunity is the most common phenotype with eosinophil-associated T2-mediated immunity in a minority and autoimmunity observed in more severe disease. Biomarkers have enabled targeted anti-inflammatory strategies and revealed that corticosteroids are most effective in those with evidence of eosinophilic inflammation, whereas, in contrast to severe asthma, response to anti-interleukin-5 biologicals in COPD has been disappointing, with smaller benefits for the same intensity of eosinophilic inflammation questioning its role in COPD. Biological therapies beyond T2-mediated inflammation have not demonstrated benefit and in some cases increased risk of infection, suggesting that neutrophilic inflammation and inflammasome activation might be largely driven by bacterial colonisation and dysbiosis. Herein we describe current and future biomarker approaches to assess inflammation in COPD and how this might reveal tractable approaches to precision medicine and unmask important host–environment interactions leading to airway inflammation.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Gabriella H. Long ◽  
Thomas Southworth ◽  
Umme Kolsum ◽  
Gavin C. Donaldson ◽  
Jadwiga A. Wedzicha ◽  
...  

AbstractBlood eosinophils are a predictive biomarker of inhaled corticosteroid response in chronic obstructive pulmonary disease (COPD). We investigated blood eosinophil stability over 1 year using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 thresholds of < 100, 100- < 300 and ≥ 300 eosinophils/μL in 225 patients from the COPDMAP cohort. Blood eosinophils showed good stability (rho: 0.71, p < 0.001, ICC 0.84), and 69.3% of patients remained in the same eosinophil category at 1 year. 85.3% of patients with eosinophils < 100 cells/μL had stable counts. The majority of blood eosinophil counts remain stable over 1 year using the GOLD 2019 thresholds.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanan Cui ◽  
Wenye Zhang ◽  
Yiming Ma ◽  
Zijie Zhan ◽  
Yan Chen

Abstract Background The clinical value of blood eosinophils and their stability in chronic obstructive pulmonary disease (COPD) remains controversial. There are limited studies on association between the stability of blood eosinophils in acute exacerbation of COPD (AECOPD) and clinical outcomes. This study aimed to evaluate the stability of blood eosinophils in hospitalized AECOPD and its relationship to clinical outcomes. Methods This prospective observational study recruited patients hospitalized with AECOPD from November 2016 to July 2020. The eligible patients were divided into four groups according to their blood eosinophil counts at admission and discharge: persistently < 300 cells/μl (LL), < 300 cells/μl at admission but ≥ 300 cells/µl at discharge (LH), ≥ 300 cells/μl at admission but < 300 cells/µl at discharge (HL), and persistently ≥ 300 cells/μl (HH). Cox hazard analyses were used to study the association between eosinophil changes and exacerbations or mortality. Results In 530 patients included, 90 (17.0%) had a high blood eosinophil count (BEC) ≥ 300 cells/µl at admission but 32 (35.6%) of them showed a decreased BEC at discharge. The proportions and distribution for group LL, LH, HL, and HH were 381 (71.9%), 59 (11.1%), 32 (6.0%), and 58 (10.9%), respectively. During hospitalization, the LH group had a higher C-reactive protein level, higher rate of intensive care unit (ICU) admission, and higher total cost. The length of hospital stay of the LH group was longer compared with group LL, HL, or HH (P = 0.002, 0.017, and 0.001, respectively). During a follow-up of 12 months, the HH group was associated with a higher risk of moderate-to-severe exacerbations compared to the LL group (hazard ratio 2.00, 95% confidence interval 1.30–3.08, P = 0.002). Eosinophil changes had no significant association with mortality at 12 months. Sensitivity analyses in patients without asthma and without use of systemic corticosteroids prior to admission did not alter the results. Conclusions More attention should be paid to the LH group when evaluating the short-term prognosis of AECOPD. A persistently high BEC was a risk factor for long-term exacerbations. Eosinophil changes during hospitalization could help to predict outcomes.


2019 ◽  
Vol 5 (1) ◽  
pp. 00248-2018
Author(s):  
Tom M.A. Wilkinson ◽  
Emmanuel Aris ◽  
Simon C. Bourne ◽  
Stuart C. Clarke ◽  
Mathieu Peeters ◽  
...  

The association between exacerbation aetiology and exacerbation frequency is poorly understood.We analysed 2-year follow-up data from a prospective observational study of patients with chronic obstructive pulmonary disease (COPD) (www.clinicaltrials.gov identifier number NCT01360398) to evaluate year-to-year variation in exacerbation frequency and related aetiology. A total of 127 patients underwent blood and sputum sampling monthly and at exacerbation to detect respiratory infections and eosinophilic inflammation; 103 continued into year 2 and 88 completed both years.The most common bacterial species at stable state and exacerbation was Haemophilus influenzae. Among infrequent exacerbators (one exacerbation per year), the incidence of viral infection at exacerbation was high (60.0% (95% CI 35.1–81.7%) in year 1 and 78.6% (53.4–94.2%) in year 2). Those with more frequent exacerbations tended to have higher relative incidence of bacterial than viral infection. Patients with at least two additional exacerbations in year 2 versus year 1 had a higher risk of H. influenzae colonisation at stable state than those with at least two fewer exacerbations, as detected by culture (OR 1.43 (95% CI 0.71–2.91) versus 0.63 (0.40–1.01), p=0.06) and PCR (1.76 (95% CI 0.88–3.51) versus 0.56 (0.37–0.86), p<0.01). This was not seen with other infection types or eosinophilic inflammation.Analysis of the same cohort over 2 years showed, for the first time, that changes in yearly COPD exacerbation rate may be associated with variations in H. influenzae colonisation.


Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 236
Author(s):  
Pradeesh Sivapalan ◽  
András Bikov ◽  
Jens-Ulrik Jensen

Treating patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves administering systemic corticosteroids. The many unwanted side effects associated with this treatment have led to increased interest in minimising the accumulated corticosteroid dose necessary to treat exacerbations. Studies have shown that short-term treatment with corticosteroids is preferred, and recent trials have shown that biomarkers can be used to further reduce exposure to corticosteroids. Interestingly, high eosinophil counts in patients with acute exacerbations of COPD are indicative of an eosinophilic phenotype with a distinct response to treatment with corticosteroids. In addition, post-hoc analysis of randomised control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to inhaled corticosteroids in stable COPD. In this review, we examine the studies on this topic, describe how blood eosinophil cell count may be used as a biomarker to guide treatment with corticosteroids, and identify some relevant challenges.


Author(s):  
Mitha Al Sibani ◽  
Abdullah M. Al Alawi ◽  
Jamal Al Aghbari

Objectives: An elevated peripheral blood eosinophil (PBE) count during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a potential predictor of treatment responsiveness and future exacerbation risk. This study aimed to evaluate the prevalence and clinical significance of elevated PBE counts in hospitalized patients with AECOPD in Oman. Methods: This single-center retrospective study included all patients with AECOPD who were admitted to Sultan Qaboos University Hospital between January 2017 and July 2019. The patients were classified as having eosinophilic or noneosinophilic 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. Results: Of 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 the groups were treated with inhaled and oral steroids. The need for mechanical ventilation did not differ between the groups. Conclusion: Eosinophilia 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. Keywords: Chronic Obstructive Pulmonary disease (COPD); Eosinophils; Steroids; length of stay; hospital readmission.


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