Eosinophilia, Frequent Exacerbations, and Steroid Response in Chronic Obstructive Pulmonary Disease

Calverley, Peter M.A.; Tetzlaff, Kay; Vogelmeier, Claus; Fabbri, Leonardo M.; Magnussen, H; Wouters, Emiel F.M.; Mezzanotte, William S.; Disse, Bernd; Finnigan, Helen; Asijee, Guus M.; Hallmann, Christoph; Watz, Henrik

doi:10.1164/rccm.201612-2525le

Cited by 107 publications

(85 citation statements)

References 7 publications

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“…However, the difference between LABA‐LAMA and ICS‐LABA was less at blood eosinophils of ≥300/μL. Furthermore, COPD patients with a history of severe exacerbations despite treatment with ICS, LAMA and LABA did not show any increase in exacerbations following ICS withdrawal unless blood eosinophils were ≥4% . The general consensus is that if blood eosinophils are >300/μL or >4%, ICS treatment may further reduce exacerbations when added to LABA and LAMA therapy, and in these patients it may be convenient to give these treatments as a triple fixed‐dose combination inhaler .…”

Section: Eosinophilic Copdmentioning

confidence: 99%

Inflammatory endotypes in COPD

Barnes

2019

Allergy

181

155

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Chronic obstructive pulmonary disease (COPD) is a major global health problem that is poorly treated by current therapies as it has proved difficult to treat the underlying inflammation, which is largely corticosteroid-resistant in most patients. Although rare genetic endotypes of COPD have been recognized, despite the clinical heterogeneity of COPD, it has proved difficult to identify distinct inflammatory endotypes.Most patients have increased neutrophils and macrophages in sputum, reflecting the increased secretion of neutrophil and monocyte chemotactic mediators in the lungs.However, some patients also have increased eosinophils in sputum and this may be reflected by increased blood eosinophils. Increased blood and sputum eosinophils are associated with more frequent exacerbations and predict a good response to corticosteroids in reducing and treating acute exacerbations. Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia is uncertain as, although an increase in sputum IL-5 has been detected, anti-IL-5 therapies are not effective in preventing exacerbations. More research is needed to link inflammatory endotypes to clinical manifestations and outcomes in COPD and in particular to predict response to precision medicines. K E Y W O R D Sasthma-COPD overlap, eosinophil, exacerbations, interleukin-5, macrophage, neutrophil

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Section: Eosinophilic Copdmentioning

confidence: 99%

Inflammatory endotypes in COPD

Barnes

2019

Allergy

181

155

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“…No prospective data regarding the sensitivity and specificity of these values in different populations with different a priori exacerbation risks are available. In contrast, some recent post hoc analyses of severe COPD patients with high eosinophil counts (4% or >300-400 cells per μL), notably in combination with a history of frequent exacerbations, suggest that these patients might be at increased risk of re-exacerbations/hospitalisation if ICS are withdrawn [27,28]. However, only a small minority (∼10%) of COPD patients have stable counts of >400 cells per μL (figure 1) [22].…”

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confidence: 96%

“…The most commonly proposed cut-off points have been a blood eosinophil count above and below 2% of the total white blood cell count or an absolute eosinophil count of 150-400 cells per μL, which is within the normal range (0-6% or 30-350 cells per μL) [26]. Others suggest that a more reliable threshold would be 4% or >400 cells per μL [27]. No prospective data regarding the sensitivity and specificity of these values in different populations with different a priori exacerbation risks are available.…”

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confidence: 99%

Peripheral eosinophil count as a biomarker for the management of COPD: not there yet

2017

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@ERSpublications Peripheral eosinophils are poorly reproducible; persistent peripheral eosinophilia predicts better outcomes in COPD http://ow.ly/3hvH30gnxkBCite this article as: Rabe KF, Beghé B, Fabbri LM. Peripheral eosinophil count as a biomarker for the management of COPD: not there yet. Eur Respir J 2017; 50: 1702165 [https://doi.org/10.1183/ 13993003.02165-2017.Chronic obstructive pulmonary disease (COPD) is associated with acute and chronic pulmonary as well as systemic inflammation [1]. Anti-inflammatory treatments, such as inhaled corticosteroids (ICS) and oral roflumilast, are recommended for COPD patients [2]. These drugs are effective agents for the prevention of COPD exacerbations and improvement of lung function and have various effects on health status, but they are associated with adverse events, the most concerning being pneumonia (ICS) and diarrhoea (roflumilast).It has been recognised for many years that some patients with COPD have eosinophilic airway inflammation both in a stable state [3] and during exacerbations [4]. More recently, the Copenhagen City Lung study strongly suggested that a high peripheral blood eosinophil count (>340 cells per µL) was associated with an increased risk of severe COPD exacerbations [5]. In contrast, and similar to the results of the ECLIPSE study [6] and of ZYSMAN et al. [7], both of which were conducted in patients with COPD, no increased risk of moderate-severe exacerbations was found when a threshold of 2% blood eosinophils was used [5]. Finally, contributing to the overall confusion about the role of eosinophils as a risk factor for COPD outcomes, increased blood eosinophils in patients with COPD were also associated with better lung function, improved quality of life [6,8], and even reduced mortality [9]. However, eosinopenia (counts of <0.05×10 9 per L) seemed to be associated with an increased risk of sepsis [10], worse outcomes in patients presenting to hospital with an acute exacerbation of COPD [11,12], and an increased risk of pneumonia [13].Interestingly, the subgroups of severe COPD patients who improve after taking oral steroids have eosinophilic airway inflammation, unlike the majority who do not respond to oral steroids [14]. Several post hoc analyses of recent randomised clinical trials have clearly shown that the effect of combination therapy with inhaled long-acting β-adrenoceptor agonists (LABA) and ICS [15,16] or triple therapy [17,18] is significantly increased in COPD patients with high blood eosinophil counts at baseline. One prominent exception to these findings is the FLAME (Effect of Indacaterol Glycopyronium vs Fluticasone

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“…Clinical data have suggested that elevated blood eosinophil counts, which is present in up to 40% of COPD patients (5), is a promising biomarker of response to ICS (6)(7)(8)(9). Eosinophilic airway inflammation has been associated with an increased risk of exacerbations, and patients with eosinophilic inflammation responded better to ICS therapy than non-eosinophilic patients (6,10).…”

Section: Blood Eosinophil Counts Withdrawal Of Inhaled Corticosteroimentioning

confidence: 99%

Blood Eosinophil Counts, Withdrawal of Inhaled Corticosteroids and Risk of COPD Exacerbations and Mortality in the Clinical Practice Research Datalink (CPRD)

Oshagbemi

Franssen

Kraaij

et al. 2019

COPD: Journal of Chronic Obstructive Pulmonary Disease

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Although recently introduced in the pharmacological treatment algorithm of chronic obstructive pulmonary disease (COPD), there is a need for more data supporting the use of blood eosinophil counts as a biomarker to guide inhaled corticosteroids (ICS) therapy. The aim of this study was to evaluate the risk of moderate and/or severe exacerbations and all-cause mortality in a large primary care population after withdrawal of ICS compared to continued users stratified by elevated blood eosinophil counts. In this population based cohort study, we used data from the Clinical Practice Research Datalink (CPRD) in the United Kingdom. We included subjects' aged 40 years or more who had a diagnosis of COPD. We excluded subjects with a history of asthma, pulmonary fibrosis, cardiac arrhythmia and bronchiectasis, COPD exacerbations occurring within 6 weeks prior to index date, or with a myocardial infarction within 3 months prior to index date. Continuous users were subjects who received their most recent ICS prescription within 3 months before the start of an interval. ICS withdrawals were those who discontinued ICS for more than 3 months. We evaluated the risk of moderate and/or severe exacerbations and all-cause mortality among subjects with various blood eosinophil thresholds who withdrew from ICS compared to continuous ICS users with elevated blood eosinophil levels using Cox regression analysis adjusted for potential confounders. We identified 48,157 subjects diagnosed with COPD between 1 January 2005 to 31 January 2014. Withdrawal of ICS was not associated with an increased risk of moderate-to-severe exacerbations among subjects with absolute blood eosinophil counts !0.34 Â 10 9 cells/L [adjusted hazard ratio (adj. HR) 0.72; 95% confidence interval (CI) 0.63-0.81] or relative counts ! 4.0% (adj. HR 0.72; 95% CI: 0.66-0.78). Similarly, withdrawal of ICS was not associated with an increased risk of severe exacerbations among subjects with absolute blood eosinophil !0.34 Â 10 9 cells/L (adj. HR 0.82; 95% CI: 0.61-1.10) or relative blood eosinophil counts !4.0% (adj. HR 0.80; 95% CI: 0.61-1.04). No increased risk of all-cause mortality was observed among subjects who withdrew from ICS irrespective of elevated absolute or relative blood eosinophil counts. In a real-world primary care population, we did not observe an increased risk of moderate and/or severe COPD exacerbations or all-cause mortality among subjects with eosinophilia who withdrew their use of ICS.

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Eosinophilia, Frequent Exacerbations, and Steroid Response in Chronic Obstructive Pulmonary Disease

Cited by 107 publications

References 7 publications

Inflammatory endotypes in COPD

Inflammatory endotypes in COPD

Peripheral eosinophil count as a biomarker for the management of COPD: not there yet

Blood Eosinophil Counts, Withdrawal of Inhaled Corticosteroids and Risk of COPD Exacerbations and Mortality in the Clinical Practice Research Datalink (CPRD)

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