Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD

Mike Lonergan; Alison J. Dicker; Megan L. Crichton; Holly R. Keir; Melissa K. Van Dyke; Hana Mullerova; Bruce E. Miller; Ruth Tal-Singer; James D. Chalmers

doi:10.1186/s12931-020-01436-7

Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD

Mike Lonergan (Lead / Corresponding author), Alison J. Dicker (Lead / Corresponding author), Megan L. Crichton, Holly R. Keir, Melissa K. Van Dyke, Hana Mullerova, Bruce E. Miller, Ruth Tal-Singer, James D. Chalmers (Lead / Corresponding author)

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Abstract

Background: Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).

Methods: In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy.

Results: 178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/μL (IQR 4000-7000cells/μL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/μL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs. 5%, P < 0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.

Conclusion: High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.

Original language	English
Article number	166
Number of pages	10
Journal	Respiratory Research
Volume	21
DOIs	https://doi.org/10.1186/s12931-020-01436-7
Publication status	Published - 1 Jul 2020

Keywords

COPD
Mortality
Eosinophil
Neutrophil
Microbiome

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1186/s12931-020-01436-7Licence: CC BY

Final Published VersionFinal published version, 1.1 MBLicence: CC BY

Cite this

@article{f7b58047a41c4f9e92d43fb044a1bff9,

title = "Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD",

abstract = "Background: Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).Methods: In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy.Results: 178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/μL (IQR 4000-7000cells/μL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/μL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs. 5%, P < 0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.Conclusion: High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.",

keywords = "COPD, Mortality, Eosinophil, Neutrophil, Microbiome",

author = "Mike Lonergan and Dicker, {Alison J.} and Crichton, {Megan L.} and Keir, {Holly R.} and {Van Dyke}, {Melissa K.} and Hana Mullerova and Miller, {Bruce E.} and Ruth Tal-Singer and Chalmers, {James D.}",

note = "Funding Information: ML, AJD, MLC, HRK report no real or perceived conflicts of interest relating to this manuscript. MKVD and HM were employees of Glaxosmithkline during the study period. BEM is an employee and shareholder of Glaxosmithkline. RTS was an employee and shareholder of Glaxosmithkline during the study period. JDC reports receiving a grant from Glaxosmithkline for this work; additional research grants for COPD studies from Glaxosmithkline, Boehringer-Ingelheim, Astrazeneca and Pfizer, additional research grants for Bronchiectasis research studies from Bayer Healthcare and Grifols and personal fees from Napp and Aradigm corporation. Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2020",

month = jul,

day = "1",

doi = "10.1186/s12931-020-01436-7",

language = "English",

volume = "21",

journal = "Respiratory Research",

issn = "1465-9921",

publisher = "Springer Verlag",

}

TY - JOUR

T1 - Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD

AU - Lonergan, Mike

AU - Dicker, Alison J.

AU - Crichton, Megan L.

AU - Keir, Holly R.

AU - Van Dyke, Melissa K.

AU - Mullerova, Hana

AU - Miller, Bruce E.

AU - Tal-Singer, Ruth

AU - Chalmers, James D.

N1 - Funding Information: ML, AJD, MLC, HRK report no real or perceived conflicts of interest relating to this manuscript. MKVD and HM were employees of Glaxosmithkline during the study period. BEM is an employee and shareholder of Glaxosmithkline. RTS was an employee and shareholder of Glaxosmithkline during the study period. JDC reports receiving a grant from Glaxosmithkline for this work; additional research grants for COPD studies from Glaxosmithkline, Boehringer-Ingelheim, Astrazeneca and Pfizer, additional research grants for Bronchiectasis research studies from Bayer Healthcare and Grifols and personal fees from Napp and Aradigm corporation. Publisher Copyright: © 2020 The Author(s).

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Background: Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).Methods: In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy.Results: 178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/μL (IQR 4000-7000cells/μL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/μL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs. 5%, P < 0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.Conclusion: High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.

AB - Background: Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC).Methods: In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy.Results: 178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/μL (IQR 4000-7000cells/μL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P < 0.001) than those with BNC in the normal range (2000-6000cells/μL). People with elevated BNC were more likely to be classified as GOLD D (46% v 33% P < 0.001), have more exacerbations (mean 2.3 v 1.3/year, P < 0.001), and were more likely to have severe exacerbations (13% vs. 5%, P < 0.001) in the following year. Eosinophil counts were much less predictive of these outcomes. In a sub-cohort (N = 276), patients with elevated BNC had increased relative abundance of Proteobacteria and reduced microbiome diversity.Conclusion: High BNC may provide a useful indicator of risk of exacerbations and mortality in COPD patients.

KW - COPD

KW - Mortality

KW - Eosinophil

KW - Neutrophil

KW - Microbiome

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U2 - 10.1186/s12931-020-01436-7

DO - 10.1186/s12931-020-01436-7

M3 - Article

C2 - 32611352

SN - 1465-9921

VL - 21

JO - Respiratory Research

JF - Respiratory Research

M1 - 166

ER -

Blood neutrophil counts are associated with exacerbation frequency and mortality in COPD

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