The different phenotypes of COPD

2021 ◽  
Author(s):  
Ahmed Yousuf ◽  
Hamish McAuley ◽  
Omer Elneima ◽  
Christopher E Brightling
Keyword(s):  
Biologic Therapy ◽  
Stable State ◽  
Symptom Burden ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Eosinophilic Inflammation ◽  
Significant Morbidity ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Eosinophil Counts

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.

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 ◽  
...  
Keyword(s):  
Stable State ◽  
Area Under The Curve ◽  
Response To Treatment ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Eosinophilic Inflammation ◽  
Obstructive Pulmonary Disease ◽  
Increased Risk ◽  
New Treatment ◽  
The Stability

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.

scholarly journals Blood eosinophil count-guided corticosteroid therapy and as a prognostic biomarker of exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204062232110287
Author(s):  
Tao Liu ◽  
Zi-Jian Xiang ◽  
Xiao-Meng Hou ◽  
Jing-Jing Chai ◽  
Yan-Li Yang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Prognostic Biomarker ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
The Stability

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.

scholarly journals Antiviral immunity is impaired in COPD patients with frequent exacerbations

2019 ◽  
Vol 317 (6) ◽  
pp. L893-L903 ◽  
Author(s):  
Aran Singanayagam ◽  
Su-Ling Loo ◽  
Maria Calderazzo ◽  
Lydia J. Finney ◽  
Maria-Belen Trujillo Torralbo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Treatment Options ◽  
Stable State ◽  
Innate Immune ◽  
Chronic Obstructive ◽  
Type I ◽  
Obstructive Pulmonary Disease ◽  
Immune Mediators ◽  
Copd Patients

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.

scholarly journals Stability in eosinophil categorisation during subsequent severe exacerbations of COPD

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
Keyword(s):  
Treatment Strategies ◽  
Stable State ◽  
Total Leucocyte Count ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Obstructive Pulmonary Disease ◽  
Blood Eosinophil Count ◽  
Acute Exacerbations ◽  
The Stability ◽  
Personalised Treatment

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.

scholarly journals Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Anaëlle Muggeo ◽  
Jeanne-Marie Perotin ◽  
Audrey Brisebarre ◽  
Sandra Dury ◽  
Valérian Dormoy ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Clinical Symptoms ◽  
Bacterial Load ◽  
Stable State ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Mass Spectrometry Identification

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (107 vs. 105 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories.

scholarly journals Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 9 (8) ◽  
pp. 2670
Author(s):  
Keiji Oishi ◽  
Kazuto Matsunaga ◽  
Toshihiro Shirai ◽  
Keita Hirai ◽  
Yasuhiro Gon
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Stable State ◽  
Epidemiologic Studies ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Blood Eosinophils ◽  
The Relationship

Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression of Type2 inflammation in the airway, and this subset was associated with the inhaled corticosteroid (ICS) response. Interestingly enough, the relationship between COPD and diseases associated with Type2 inflammation from the perspective of impaired lung development is increasingly highlighted by recent epidemiologic studies on the origin of COPD. Therefore, many researchers have shown an interest in the prevalence and the role of existent Type2 biomarkers such as sputum and blood eosinophils, exhaled nitric oxide fraction, and atopy, not only in asthma but also in COPD. Although the evidence about Type2 biomarkers in COPD is inconsistent and less robust, Type2 biomarkers have shown some potential when analyzing various clinical outcomes or therapeutic response to ICS. In this article, we review the existent and emerging Type2 biomarkers with clinically higher applicability in the management of COPD.

Absolute Blood Eosinophil Counts to Guide Inhaled Corticosteroids Therapy Among Patients with COPD: Systematic Review and Meta-analysis

2019 ◽  
Vol 20 (16) ◽  
pp. 1670-1679 ◽  
Author(s):  
Olorunfemi A. Oshagbemi ◽  
Jephthah O. Odiba ◽  
Abraham Daniel ◽  
Ismaeel Yunusa
Keyword(s):  
Systematic Review ◽  
Eosinophil Count ◽  
Inhaled Corticosteroids ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Blood Eosinophil Count ◽  
Copd Patients ◽  
Phenotypic Group ◽  
Increased Risk ◽  
Eosinophil Counts

Introduction: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 recommends the use of absolute blood eosinophil count as a guide for the escalation and de-escalation of inhaled corticosteroids (ICS) in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). We evaluated the risk of moderate or severe exacerbations among patients escalating and de-escalating ICS therapy by absolute blood eosinophil thresholds in this systematic review. Methods: Through a comprehensive literature search of Pubmed/MEDLINE, EMBASE, and clinical trial sites up to April 2019, we identified relevant studies. We used generic inverse variance method with fixed-effects estimates to compare the risk of moderate or severe exacerbations among COPD patients with elevated blood eosinophil counts exposed to inhaled corticosteroids (ICS) versus non-ICS treatments groups expressed as risk ratios. Results: Ten studies (8 randomised control trials and 2 observational studies) were included, with a total of 85,059 COPD patients. In our pooled analysis, we found an overall reduction in risk of moderate or severe exacerbations in patients with absolute blood eosinophil thresholds ranging from ≥ 100 to ≥ 340 cells/µL among patients escalating ICS (RR, 0.77, 95% CI, 0.73-0.81). For studies evaluating the effects of de-escalation of ICS on moderate to severe exacerbations using blood eosinophil thresholds of ≥ 300 to ≥ 340 cells/µL had an increased risk of moderate or severe exacerbations following the de-escalation of ICS (RR, 1.66, 95% CI, 1.31-2.10). Conclusion: This study confirms the validity of the recommended absolute blood eosinophil count thresholds for the escalation and de-escalation of ICS among COPD patients. However, this recommendation is for COPD patients with prior exacerbations rather than among newly diagnosed COPD patients as observed in this study. COPD patients with current or past history of asthma represent a unique phenotypic group which should be further evaluated.

scholarly journals Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 202 (5) ◽  
pp. 660-671 ◽  
Author(s):  
Dave Singh ◽  
Mona Bafadhel ◽  
Christopher E. Brightling ◽  
Frank C. Sciurba ◽  
Jeffrey L. Curtis ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Clinical Trials ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Obstructive Pulmonary Disease ◽  
Eosinophil Counts
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