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Neutrophil-to-lymphocyte ratio, blood eosinophils and COPD exacerbations: a cohort study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.ORCID iD: 0000-0002-2409-1707
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.ORCID iD: 0000-0001-5093-6980
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.ORCID iD: 0000-0002-0080-5023
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.ORCID iD: 0000-0002-3107-4462
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2021 (English)In: ERJ Open Research, E-ISSN 2312-0541, Vol. 7, no 4Article in journal (Refereed) Published
Abstract [en]

Background Blood neutrophil-to-lymphocyte ratio (NLR) and blood eosinophils (B-Eos) are emerging biomarkers in COPD. This study examined whether they could predict acute exacerbations of COPD (AECOPDs), and determined their longitudinal stability.Methods In this closed cohort study, Swedish subjects with spirometry-verified COPD attended three yearly visits in a stable phase of the disease. Blood cell counts, spirometry and questionnaire-assessed AECOPD-history (worsening of COPD leading to an unscheduled visit and/or use of antibiotics and/or oral corticosteroids) were collected at each visit.Results Of 466 included subjects 57% were female. Baseline mean±sd forced expiratory volume in 1 s was 58±17% predicted. High NLR (≥3.0) was more common in subjects with previous AECOPDs than in those without (33.5% versus 20.4%, p=0.002). In two-level mixed-effects logistic regression models adjusted for confounders, NLR as a continuous variable (OR 1.20, 95% CI 1.04–1.38) and B-Eos ≥300 cells·µL−1 (OR 1.54, 95% CI 1.06–2.24) were associated with future AECOPDs. In 386 subjects with blood cell data available at all three visits, the intraclass correlation coefficient for NLR was 0.61 (95% CI 0.56–0.66) and for B-Eos 0.69 (95% CI 0.64–0.73). NLR was persistently ≥3.0 in 10.6% and B-Eos was persistently ≥300 cells·µL−1 in 15.3%.Conclusions Stable phase NLR and B-Eos were associated with future AECOPDs. NLR on its own is probably not useful to predict AECOPDs but might be included in a risk scoring index. A minority of subjects with COPD had persistently elevated stable-phase NLR or B-Eos, and the biomarkers showed fair longitudinal reliability.

Place, publisher, year, edition, pages
ERS Publications , 2021. Vol. 7, no 4
National Category
Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-463033DOI: 10.1183/23120541.00471-2021ISI: 000769759500054PubMedID: 34988219OAI: oai:DiVA.org:uu-463033DiVA, id: diva2:1624786
Funder
Swedish Heart Lung FoundationAvailable from: 2022-01-04 Created: 2022-01-04 Last updated: 2024-02-22Bibliographically approved
In thesis
1. Chronic obstructive pulmonary disease: exacerbations and mortality: Prognostic value of biomarkers and comorbidities
Open this publication in new window or tab >>Chronic obstructive pulmonary disease: exacerbations and mortality: Prognostic value of biomarkers and comorbidities
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. COPD is associated with systemic inflammation, and comorbidities are common. A characteristic feature is acute exacerbations (AECOPDs), i.e., episodes of worsening symptoms. AECOPDs are associated with increased mortality.

Aim: To find prognostic risk factors for COPD mortality and AECOPDs, focusing on comorbidities and inflammatory biomarkers.

Methods: In Paper I, associations between comorbidities, pharmacological treatment, and mortality were analysed in a real-world cohort of almost 18,000 primary care COPD patients. Data from medical records and national registers were analysed in Cox proportional hazards regressions.

Papers II–IV were based on the Tools Identifying Exacerbations (TIE) cohort study of 572 COPD patients recruited from primary and secondary care in three Swedish regions. Participants were invited to three yearly visits, including phlebotomy, spirometry, and health questionnaires.

In Paper II, the ability of blood neutrophil-to-lymphocyte ratio (NLR) and eosinophils (B-Eos) to predict AECOPDs was analysed with mixed-effects logistic regressions.

In Paper III, the ability of C-reactive protein (CRP), fibrinogen, blood leukocytes (B-Leu), and four blood cell indices to predict AECOPDs was analysed with ordinal logistic regressions.

In Paper IV, an algorithm for clinical phenotyping previously developed to predict mortality was studied. The algorithm’s ability to predict AECOPDs and mortality was analysed with Cox proportional hazards regressions; additionally, the identified phenotypes were analysed concerning differences in blood-based inflammatory biomarkers.

Results: Several comorbidities, including heart diseases, were associated with increased mortality risk. Some pharmacological treatments were associated with increased or decreased mortality risk (Paper I). NLR, B-Eos, CRP, fibrinogen, and B-Leu (Papers II–III) predicted AECOPDs after adjustment for confounders, whereas other blood cell indices were of limited value (Paper III). The clinical phenotyping algorithm predicted AECOPDs and mortality, and the phenotypes had different patterns of inflammatory biomarkers (Paper IV).

Conclusions: Comorbidities, particularly heart diseases, are substantial risk factors for mortality in COPD and should be an integral part of management of COPD patients. NLR, B-Eos, CRP, fibrinogen, and B-Leu are independent predictors of AECOPDs and should be further investigated as parts of, e.g., risk prediction tools. A previously developed algorithm for clinical phenotyping predicts mortality and AECOPDs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2024. p. 95
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2021
Keywords
COPD, exacerbations, mortality, biomarkers, comorbidity
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
urn:nbn:se:uu:diva-523303 (URN)978-91-513-2044-1 (ISBN)
Public defence
2024-04-12, Gunnesalen, Uppsala University Hospital/Akademiska Sjukhuset, Entrance 10, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2024-03-21 Created: 2024-02-22 Last updated: 2024-03-21

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Ellingsen, JensJanson, ChristerBröms, KristinaLisspers, KarinStällberg, BjörnHögman, MarieannMalinovschi, Andrei

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