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

Kim, Viktoriya L.; Coombs, Ngaire; Staples, Karl J.; Ostridge, Kristoffer; Williams, Nicholas; Wootton, Stephen A.; Devaster, Jeanne-Marie; Aris, Emmanuel; Clarke, Stuart C.; Tuck, Andrew; Bourne, Simon; Wilkinson, Tom

doi:10.1183/13993003.00853-2017

Cited by 73 publications

(79 citation statements)

References 30 publications

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“…For instance, the treatable traits concept applied to bronchiectasis should recognise that airway infection is only one of many treatable traits in a given patient and, therefore, allows us to understand why antibiotic treatment may not improve outcomes in an individual in whom symptoms or exacerbations are driven by a different treatable trait (e.g. upper airway disease, eosinophilia, fungal allergy or comorbidities) [21][22][23][24]. This strategy may also help in understanding why randomised clinical trials have shown inconsistent results despite similar design and well-defined cohorts.…”

Section: Chronic Pseudomonas Infectionmentioning

confidence: 99%

Treatable traits in bronchiectasis

et al. 2018

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]. The diagnostic label "bronchiectasis" describes the existence of localised and permanent airway dilation, but when used to describe a disease it includes a heterogeneous group of disorders that differ significantly in terms of aetiological, clinical, radiological, functional and microbial features [1]. Using cluster analysis, some previous studies have attempted to identify distinct "clinical phenotypes" in patients with bronchiectasis [2-4] (defined as "a single or combination of disease attributes that describe differences between patients that are related to clinically meaningful outcomes" [5]). By and large, however, these studies did not consider the underlying biology or response to therapy (i.e. the underlying endotype(s) [6]). Potential endotypes in bronchiectasis include immunodeficiency, ciliary dyskinesia, infection (with typical bacteria and non-tuberculous mycobacteria (NTM)), hypersensitivity to fungi and autoimmunity. Importantly, all of them can potentially become therapeutic targets [7]. The main treatment goals in bronchiectasis are to reduce symptoms, prevent exacerbations and lung function decline and, ultimately, improve survival. Unfortunately, most currently available therapeutic options have shown only a modest impact on disease outcomes in randomised clinical trials [8, 9]. For instance, inhaled antibiotic treatments have, so far, produced only modest benefits in terms of reduced exacerbations or improved quality of life, suggesting that endotypes other than airway "infection" are likely to play a relevant pathogenic role [10-12]. Likewise, co-existing airways diseases are common in patients with bronchiectasis and, in fact, up to 50% of these patients have a diagnosis of co-existing asthma or chronic obstructive pulmonary disease (COPD) [13, 14]. All in all, the complexity of bronchiectasis is poorly adapted to the "one size fits all" approach of current clinical guidelines. The coexistence in the same patient of different endotypes, clinical phenotypes and exposures requires a more precise approach to both assessment and therapy. The concept of "treatable traits" was originally proposed in 2016 by AGUSTI et al. [15] in the European Respiratory Journal as a way toward precision medicine of airway diseases. These authors argued that the current airways disease diagnostic labels are imprecise, often overlap and lead to empirical therapy. They proposed that a biomarker-directed approach, based on the recognition of clinical phenotype and endotypes, can help to personalised treatment options which, hopefully, may result in better clinical outcomes. In the original manuscript on treatable traits, bronchiectasis was considered as a potential trait in patients with a diagnostic label of asthma or COPD. Here, we leverage from the treatable traits concept [15] and suggest that patients with bronchiectasis, with or without co-existing COPD and asthma, represent a heterogeneous group of patients who also present multiple treatable traits, many of which go

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Section: Chronic Pseudomonas Infectionmentioning

confidence: 99%

Treatable traits in bronchiectasis

et al. 2018

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“…Interestingly, the presence of greater sputum eosinophil counts has been associated with less bacterial colonization in the stable state (19,20). Of note, the lower respiratory tract microbiome of patients with lower BEC, as assessed by sputum, may have fewer proteobacteria and an altered proteobacteria:firmicutes ratio (21).…”

Section: Introductionmentioning

confidence: 99%

Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease

Singh

Bafadhel

Brightling

et al. 2020

Am J Respir Crit Care Med

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“…Our finding is consistent with previous studies. In AERIS cohort, eosinophilic inflammation was more prevalent at exacerbation in patients with predominantly raised eosinophils at stable COPD [9]. Also, we demonstrated that the best cut-off value for the prediction of eosinophilic COPD exacerbation based on blood eosinophil count ≥ 2% or ≥ 300 cells/µL was blood eosinophil count ≥ 300 cells/µL in both cases.…”

Section: Discussionmentioning

confidence: 60%

“…In the ECLIPSE study, half of the patients were an intermittent group with variable eosinophil counts that oscillated above and below 2% [20]. However, Kim et al reported that blood eosinophils at a time-point were a useful predictor of being in the persistent eosinophilia group over the next 12 months demonstrating longitudinal stability of blood eosinophilic inflammation within individuals [9].…”

Section: Discussionmentioning

confidence: 99%

“…Blood eosinophils at a time-point were a useful predictor of being in the persistent eosinophilia group over the next 12 months demonstrating longitudinal stability of blood eosinophilic inflammation within individuals. Eosinophilic inflammation groups based on blood eosinophils ≥ 2% had higher eosinophilic exacerbation rates than intermittent eosinophilic or rarely eosinophilic groups [9].…”

Section: Introductionmentioning

confidence: 88%

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The prediction of eosinophilic exacerbation by eosinophil levels stratified in stable COPD

Kang

Kim

et al. 2020

Preprint

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Background Blood eosinophil count may predict treatment response in patients with chronic obstructive pulmonary disease (COPD) during acute exacerbations (AE). However, the ability and thresholds of blood eosinophil counts in stable status to predict eosinophilic AECOPD have not been completely investigated. Methods This was a retrospective multicenter study performed January 2010 to December 2014. COPD subjects hospitalized with exacerbations, were included. Blood samples were obtained at the time of AE and stable disease at outpatient clinic before or after admission. We identified a blood eosinophil count cut-off point at stable COPD, either taken as a percentage or as absolute value, for identification of predicting blood eosinophil count at AECOPD. Results There was significant positive correlation of eosinophil counts between stable COPD and AECOPD. The best cut-off value of blood eosinophil count in stable status for the prediction of eosinophilic COPD exacerbation based on blood eosinophil count ≥ 2% was 300 cells/µL (area under the ROC curve [AUC] 0.614, P = 0.001, 39% sensitivity, 83.8% specificity). When the eosinophilic COPD exacerbation was based on blood eosinophil count ≥ 300 cells/µL, the best cut-off value of blood eosinophil count in stable status for the prediction of eosinophilic COPD exacerbation was also 300 cells/uL (AUC 0.634, P = 0.046, 45.8% sensitivity, 80.9% specificity). Conclusions We demonstrated association between blood eosinophil counts at stable COPD and those with AECOPD. The thresholds of blood counts at stable COPD to predict eosinophilic exacerbations was 300 cells/µL. Further and prospective studies in other populations should validate our results.

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

Cited by 73 publications

References 30 publications

Treatable traits in bronchiectasis

Treatable traits in bronchiectasis

Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease

The prediction of eosinophilic exacerbation by eosinophil levels stratified in stable COPD

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