Association between COPD exacerbations and lung function decline during maintenance therapy

Marjan Kerkhof; Jaco Voorham; Paul Dorinsky; Claudia Cabrera; Patrick Darken; Janwillem WH Kocks; Mohsen Sadatsafavi; Don D. Sin; Victoria Carter; David B. Price

doi:10.1136/thoraxjnl-2019-214457

Association between COPD exacerbations and lung function decline during maintenance therapy

Marjan Kerkhof, Jaco Voorham, Paul Dorinsky, Claudia Cabrera, Patrick Darken, Janwillem WH Kocks, Mohsen Sadatsafavi, Don D. Sin, Victoria Carter, David B. Price^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

13 Downloads (Pure)

Abstract

Background: Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study. Methods: The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline. Effect modification by blood eosinophils was studied through interaction terms.ResultsL Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1mL/ year (6.6 to 23.6) to 4.3mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS. Conclusion: Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.

Original language	English
Pages (from-to)	744-753
Number of pages	10
Journal	Thorax
Volume	75
Issue number	9
Early online date	12 Jun 2020
DOIs	https://doi.org/10.1136/thoraxjnl-2019-214457
Publication status	Published - 30 Sept 2020

Bibliographical note

Acknowledgements: Writing and editorial support was provided by Dr Julia Granerod, supported by the Observational and Pragmatic Research Institute Pte. Ltd (OPRI).
Funding: This study was funded by AstraZeneca.Data availability statement: Data may be obtained from a third party and are not publicly available. The dataset supporting the conclusions of this article was derived from the Clinical Practice Research Datalink (www.cprd.com) and the Optimum Patient Care Research Database (www.opcrd.co.uk). The CPRD has
broad National Research Ethics Service Committee (NRES) ethics approval for purely observational research using the primary care data and established data
linkages. The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymised research data (Research Ethics Committee reference: 5/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD, and the Independent Scientific Advisory Committee (ISAC) for the CPRD. The authors do not have permission to give public access to the study dataset; researchers may request access to CPRD or OPCRD data for their own purposes. Access to CPRD can be made via the CPRD website (https://www.cprd.com/researcher/) or via the enquiries email enquiries@cprd. com. Access to OCPRD can be made via the OCPRD website(https://opcrd.co.uk/our-database/data-requests/) or via the enquiries email info@opcrd.co.uk. The study was designed, implemented, and registered in accordance with the criteria of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS19879).

Keywords

COPD exacerbations
COPD pharmacology
eosinophil biology
lung physiology
OBSTRUCTIVE PULMONARY-DISEASE
IMPACT
BIOMARKER
BLOOD EOSINOPHILS
INHALED CORTICOSTEROIDS
FEV1 DECLINE

Access to Document

10.1136/thoraxjnl-2019-214457Licence: CC BY-NC

Kerkhof_et_al_BMJ_AssociationBetweenCOPD_VoR
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Final published version, 719 KBLicence: CC BY-NC

Cite this

@article{adacb42d056443929e688c6239881766,

title = "Association between COPD exacerbations and lung function decline during maintenance therapy",

abstract = "Background: Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study. Methods: The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline. Effect modification by blood eosinophils was studied through interaction terms.ResultsL Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1mL/ year (6.6 to 23.6) to 4.3mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS. Conclusion: Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.",

keywords = "COPD exacerbations, COPD pharmacology, eosinophil biology, lung physiology, OBSTRUCTIVE PULMONARY-DISEASE, IMPACT, BIOMARKER, BLOOD EOSINOPHILS, INHALED CORTICOSTEROIDS, FEV1 DECLINE",

author = "Marjan Kerkhof and Jaco Voorham and Paul Dorinsky and Claudia Cabrera and Patrick Darken and Kocks, {Janwillem WH} and Mohsen Sadatsafavi and Sin, {Don D.} and Victoria Carter and Price, {David B.}",

note = "Acknowledgements: Writing and editorial support was provided by Dr Julia Granerod, supported by the Observational and Pragmatic Research Institute Pte. Ltd (OPRI). Funding: This study was funded by AstraZeneca.Data availability statement: Data may be obtained from a third party and are not publicly available. The dataset supporting the conclusions of this article was derived from the Clinical Practice Research Datalink (www.cprd.com) and the Optimum Patient Care Research Database (www.opcrd.co.uk). The CPRD has broad National Research Ethics Service Committee (NRES) ethics approval for purely observational research using the primary care data and established data linkages. The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymised research data (Research Ethics Committee reference: 5/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD, and the Independent Scientific Advisory Committee (ISAC) for the CPRD. The authors do not have permission to give public access to the study dataset; researchers may request access to CPRD or OPCRD data for their own purposes. Access to CPRD can be made via the CPRD website (https://www.cprd.com/researcher/) or via the enquiries email enquiries@cprd. com. Access to OCPRD can be made via the OCPRD website(https://opcrd.co.uk/our-database/data-requests/) or via the enquiries email info@opcrd.co.uk. The study was designed, implemented, and registered in accordance with the criteria of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS19879).",

year = "2020",

month = sep,

day = "30",

doi = "10.1136/thoraxjnl-2019-214457",

language = "English",

volume = "75",

pages = "744--753",

journal = "Thorax",

issn = "0040-6376",

publisher = "BMJ Publishing Group Ltd",

number = "9",

}

TY - JOUR

T1 - Association between COPD exacerbations and lung function decline during maintenance therapy

AU - Kerkhof, Marjan

AU - Voorham, Jaco

AU - Dorinsky, Paul

AU - Cabrera, Claudia

AU - Darken, Patrick

AU - Kocks, Janwillem WH

AU - Sadatsafavi, Mohsen

AU - Sin, Don D.

AU - Carter, Victoria

AU - Price, David B.

N1 - Acknowledgements: Writing and editorial support was provided by Dr Julia Granerod, supported by the Observational and Pragmatic Research Institute Pte. Ltd (OPRI). Funding: This study was funded by AstraZeneca.Data availability statement: Data may be obtained from a third party and are not publicly available. The dataset supporting the conclusions of this article was derived from the Clinical Practice Research Datalink (www.cprd.com) and the Optimum Patient Care Research Database (www.opcrd.co.uk). The CPRD has broad National Research Ethics Service Committee (NRES) ethics approval for purely observational research using the primary care data and established data linkages. The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymised research data (Research Ethics Committee reference: 5/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD, and the Independent Scientific Advisory Committee (ISAC) for the CPRD. The authors do not have permission to give public access to the study dataset; researchers may request access to CPRD or OPCRD data for their own purposes. Access to CPRD can be made via the CPRD website (https://www.cprd.com/researcher/) or via the enquiries email enquiries@cprd. com. Access to OCPRD can be made via the OCPRD website(https://opcrd.co.uk/our-database/data-requests/) or via the enquiries email info@opcrd.co.uk. The study was designed, implemented, and registered in accordance with the criteria of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS19879).

PY - 2020/9/30

Y1 - 2020/9/30

N2 - Background: Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study. Methods: The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline. Effect modification by blood eosinophils was studied through interaction terms.ResultsL Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1mL/ year (6.6 to 23.6) to 4.3mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS. Conclusion: Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.

AB - Background: Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study. Methods: The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline. Effect modification by blood eosinophils was studied through interaction terms.ResultsL Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1mL/ year (6.6 to 23.6) to 4.3mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS. Conclusion: Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.

KW - COPD exacerbations

KW - COPD pharmacology

KW - eosinophil biology

KW - lung physiology

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - IMPACT

KW - BIOMARKER

KW - BLOOD EOSINOPHILS

KW - INHALED CORTICOSTEROIDS

KW - FEV1 DECLINE

UR - http://www.scopus.com/inward/record.url?scp=85086718934&partnerID=8YFLogxK

U2 - 10.1136/thoraxjnl-2019-214457

DO - 10.1136/thoraxjnl-2019-214457

M3 - Article

C2 - 32532852

SN - 0040-6376

VL - 75

SP - 744

EP - 753

JO - Thorax

JF - Thorax

IS - 9

ER -

Association between COPD exacerbations and lung function decline during maintenance therapy

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this