Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease

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Abstract

Introduction

Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations.

Methods

Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators.

Results

A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators.

Conclusion

Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD.

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Most cited references 34

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Chronic obstructive pulmonary disease

Marc DeCramer, Wim Janssens, Marc Miravitlles (2012)

Summary Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.

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Severe exacerbations and BODE index: two independent risk factors for death in male COPD patients.

Juan Soler-Cataluna, Miguel Martínez-García, Lourdes Sánchez … (2009)

1) To determine whether severe exacerbation of COPD is a BODE index independent risk factor for death; 2) whether the combined application of exacerbations and BODE (e-BODE index), offers greater predictive capacity than BODE alone or can simplify the model, by replacing the exercise capacity (BODEx index). A prospective study was made of a cohort of COPD patients. In addition to calculation of the BODE index we register frequency of exacerbations. An analysis was made of all-cause mortality, evaluating the predictive capacity of the exacerbations after adjusting for the BODE. These variables were also used to construct two new indexes: e-BODE and BODEx. The study included 185 patients with a mean age of 71+/-9 years, and FEV(1)% 47+/-17%. Severe exacerbation appeared as an independent adverse prognostic variable of BODE index. For each new exacerbation the adjusted mortality risk increased 1.14-fold (95% CI: 1.04-1.25). However, the e-BODE index (C statistic: 0.77, 95% CI: 0.67-0.86) didn't improve prognostic capacity of BODE index (C statistic: 0.75, 95% CI: 0.66-0.84) (p=NS). An interesting finding was that BODEx index (C statistic: 0.74, 95% CI: 0.65-0.83) had similar prognostic capacity than BODE index. Severe exacerbations of COPD imply an increased mortality risk that is independent of baseline severity of the disease as measured by the BODE index. The combined application of both parameters (e-BODE index) didn't improve the predictive capacity, but on replacing exacerbation with exercise capacity the multidimensional grading system is simplified without loss of predictive capacity.

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Is Open Access

Eosinophilic airway inflammation in COPD

Shironjit Saha, Christopher E. Brightling (2006)

Chronic obstructive pulmonary disease is a common condition and a major cause of mortality. COPD is characterized by irreversible airflow obstruction. The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation. The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages. Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%–40% of induced sputum samples from patients with stable COPD. This airway eosinophilia is increased in exacerbations. Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD. Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation. In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions. Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Chron Obstruct Pulmon Dis

Journal ID (iso-abbrev): Int J Chron Obstruct Pulmon Dis

Journal ID (publisher-id): COPD

Journal ID (pmc): copd

Title: International Journal of Chronic Obstructive Pulmonary Disease

Publisher: Dove

ISSN (Print): 1176-9106

ISSN (Electronic): 1178-2005

Publication date (Electronic): 31 March 2020

Publication date Collection: 2020

Volume: 15

Pages: 681-690

Affiliations

[1 ]Pneumology Department, Hospital Universitari Vall d´Hebron/Vall d’Hebron Institut de Recerca (VHIR) , Barcelona, Spain

[2 ]Medicine Department, Autonomous University of Barcelona (UAB) , Barcelona, Spain

[3 ]Respiratory Unit, AOU Sassari , Sassari, Italy

[4 ]Department of Pulmonary Diseases, University Medical Centre Ljubljana , Ljubljana, Slovenia

[5 ]Department of Pulmonary Diseases, Medical Faculty, Medical University of Sofia , Sofia, Bulgaria

[6 ]CIBER de Enfermedades Respiratorias (CIBERES) , Barcelona, Spain

Author notes

Correspondence: Marc Miravitlles Pneumology Department, Hospital Universitari Vall d´Hebron , P. Vall d’Hebron 119-129, Barcelona08035, SpainTel +34 934893000Fax +34 93 274 82 08 Email marcm@separ.es

[*]

These authors contributed equally to this work

Article

Publisher ID: 240720

DOI: 10.2147/COPD.S240720

PMC ID: 7127861

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

Page count

Figures: 2, Tables: 4, References: 48, Pages: 10

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease

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Abstract

Introduction

Methods

Results

Conclusion

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International Journal of COPD

Most cited references 34

Chronic obstructive pulmonary disease

Severe exacerbations and BODE index: two independent risk factors for death in male COPD patients.

Eosinophilic airway inflammation in COPD

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