Interrelationships among small airways dysfunction, neutrophilic inflammation, and exacerbation frequency in COPD
Interrelationships among small airways dysfunction, neutrophilic inflammation, and exacerbation frequency in COPD
Background
Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline.
Research Question
Is small airways disease a key feature of frequent COPD exacerbators and is this related to airway inflammation?
Study Design and Methods
Thirty nine COPD subjects defined as either frequent exacerbators ( ≥ 2 exacerbations per year, n = 17) and infrequent exacerbators (≤1 exacerbation per year, n = 22) underwent Forced Oscillation Technique (R5-R19, AX), multiple breath nitrogen washout (Scond, Sacin), plethysmography (RV/TLC), single breath transfer factor (TLCO), spirometry (FEV1%, FEV1/FVC) and paired inspiratory – expiratory CT scans to ascertain small airways disease. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions.
Results
Acinar ventilation heterogeneity (Sacin) was significantly higher in COPD FE compared to IE (P = .027). In the FE group, markers of SAD were strongly associated with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, rho = 0.560), RV/TLC (P = .004, r = 0.730) and the mean lung density of the paired CT scans (P = .018, r = 0.639).
Interpretation
Increased acinar ventilation heterogeneity may be a consequence of previous exacerbations or highlight a group of patients prone to exacerbations. Measures of SAD were strongly associated with neutrophilic inflammation in the small airways of FE supporting the hypothesis that frequent exacerbations are associated with small airway disease related to increased cellular inflammation.
COPD, exacerbation, inflammation, small airways
1391-1399
Day, Kerry
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Ostridge, Kristoffer
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Conway, Joy
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Cellura, Doriana
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Watson, Alastair
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Spalluto, Cosma Mirella
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Staples, Karl J
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Thompson, Bruce
0b7b7407-57cb-4502-9e32-152a2f3b0c2f
Wilkinson, Tom
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April 2021
Day, Kerry
8f043bbb-080d-49b3-9ee5-046f3a636ee0
Ostridge, Kristoffer
d2271bae-b078-4390-8919-8f8c0e20542c
Conway, Joy
bbe9a2e4-fb85-4d4a-a38c-0c1832c32d06
Cellura, Doriana
e4cffc4c-0e12-40e7-ad13-e90e3fb55332
Watson, Alastair
9eb79329-8d32-4ed4-b8b9-d720883e8042
Spalluto, Cosma Mirella
6802ad50-bc38-404f-9a19-40916425183b
Staples, Karl J
e0e9d80f-0aed-435f-bd75-0c8818491fee
Thompson, Bruce
0b7b7407-57cb-4502-9e32-152a2f3b0c2f
Wilkinson, Tom
8c55ebbb-e547-445c-95a1-c8bed02dd652
Day, Kerry, Ostridge, Kristoffer, Conway, Joy, Cellura, Doriana, Watson, Alastair, Spalluto, Cosma Mirella, Staples, Karl J, Thompson, Bruce and Wilkinson, Tom
(2021)
Interrelationships among small airways dysfunction, neutrophilic inflammation, and exacerbation frequency in COPD.
Chest, 159 (4), .
(doi:10.1016/j.chest.2020.11.018).
Abstract
Background
Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline.
Research Question
Is small airways disease a key feature of frequent COPD exacerbators and is this related to airway inflammation?
Study Design and Methods
Thirty nine COPD subjects defined as either frequent exacerbators ( ≥ 2 exacerbations per year, n = 17) and infrequent exacerbators (≤1 exacerbation per year, n = 22) underwent Forced Oscillation Technique (R5-R19, AX), multiple breath nitrogen washout (Scond, Sacin), plethysmography (RV/TLC), single breath transfer factor (TLCO), spirometry (FEV1%, FEV1/FVC) and paired inspiratory – expiratory CT scans to ascertain small airways disease. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions.
Results
Acinar ventilation heterogeneity (Sacin) was significantly higher in COPD FE compared to IE (P = .027). In the FE group, markers of SAD were strongly associated with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, rho = 0.560), RV/TLC (P = .004, r = 0.730) and the mean lung density of the paired CT scans (P = .018, r = 0.639).
Interpretation
Increased acinar ventilation heterogeneity may be a consequence of previous exacerbations or highlight a group of patients prone to exacerbations. Measures of SAD were strongly associated with neutrophilic inflammation in the small airways of FE supporting the hypothesis that frequent exacerbations are associated with small airway disease related to increased cellular inflammation.
Text
Interrelationships between SAD neutrophilic inflammation and exacerbation in COPD accepted CHEST
- Accepted Manuscript
More information
Accepted/In Press date: 8 November 2020
e-pub ahead of print date: 25 November 2020
Published date: April 2021
Additional Information:
Funding Information:
FUNDING/SUPPORT: This study was funded by AstraZeneca.Author contributions: K. D. had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. K. D. K. O. K. J. S. and T. W. contributed substantially to the study design, and all authors contributed to the writing of the manuscript. K. D. K. O. K. J. S. A. W. C. M. S. D. C. and T. W. collected or generated the data. All authors analyzed or interpreted the data. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: K. D. K. J. S. J. C. T. W. A. W. C. M. S. and D. C. report grants from AstraZeneca during the conduct of the study. J. C. reports personal fees from Trudell Medical outside the submitted work, and T. W. reports personal fees and other from MyMHealth, grants from GSK, grants and personal fees from AstraZeneca, grants and personal fees from Synairgen, and personal fees from BI outside the submitted work. K. O. is a paid employee of AstraZeneca. None declared (B. T.). Role of sponsors: AstraZeneca reviewed the publication, without influencing the opinions of the authors, to ensure medical and scientific accuracy and the protection of intellectual property. The corresponding author had access to all data in the study and had the final responsibility for the decision to submit the manuscript for publication. MICA II Study Group Collaborators: Anna Freeman, PhD, and Hannah Burke, BMBS. Other contributions: The authors thank all the study volunteers for their contributions toward furthering knowledge about COPD, the nursing staff in the Southampton Centre for Biomedical Research, and VIDA for the image analysis, which formed part of an academic collaboration. Additional information: The e-Appendix and e-Tables can be found in the Supplemental Materials section of the online article.
Funding Information:
FUNDING/SUPPORT: This study was funded by AstraZeneca .
Publisher Copyright:
© 2020 American College of Chest Physicians
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
Keywords:
COPD, exacerbation, inflammation, small airways
Identifiers
Local EPrints ID: 445062
URI: http://eprints.soton.ac.uk/id/eprint/445062
ISSN: 0012-3692
PURE UUID: 59b01e24-9a15-4ed9-9499-160911dabf74
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Date deposited: 18 Nov 2020 17:34
Last modified: 17 Mar 2024 06:04
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Contributors
Author:
Kerry Day
Author:
Kristoffer Ostridge
Author:
Joy Conway
Author:
Doriana Cellura
Author:
Alastair Watson
Author:
Cosma Mirella Spalluto
Author:
Bruce Thompson
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