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Interrelationships between small airways dysfunction, neutrophilic inflammation and exacerbation frequency in COPD

Interrelationships between small airways dysfunction, neutrophilic inflammation and exacerbation frequency in COPD
Interrelationships between 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
0012-3692
1391-1399
Day, Kerry
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Ostridge, Kristoffer
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Conway, Joy H.
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Cellura, Doriana
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Watson, Alastair
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Spalluto, Cosma Mirella
6802ad50-bc38-404f-9a19-40916425183b
Staples, Karl J.
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Thompson, Bruce
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Wilkinson, Tom
8c55ebbb-e547-445c-95a1-c8bed02dd652
Day, Kerry
6493b359-21cd-4068-88f4-a6e684f73316
Ostridge, Kristoffer
d2271bae-b078-4390-8919-8f8c0e20542c
Conway, Joy H.
bbe9a2e4-fb85-4d4a-a38c-0c1832c32d06
Cellura, Doriana
e4cffc4c-0e12-40e7-ad13-e90e3fb55332
Watson, Alastair
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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
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Day, Kerry, Ostridge, Kristoffer, Conway, Joy H., Cellura, Doriana, Watson, Alastair, Spalluto, Cosma Mirella, Staples, Karl J., Thompson, Bruce and Wilkinson, Tom (2021) Interrelationships between small airways dysfunction, neutrophilic inflammation and exacerbation frequency in COPD. Chest, 159 (4), 1391-1399. (doi: 10.1016/j.chest.2020.11.018).

Record type: Article

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
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More information

Accepted/In Press date: 8 November 2020
Published date: 1 April 2021
Keywords: COPD, exacerbation, inflammation, small airways

Identifiers

Local EPrints ID: 445062
URI: http://eprints.soton.ac.uk/id/eprint/445062
DOI: doi: 10.1016/j.chest.2020.11.018
ISSN: 0012-3692
PURE UUID: 59b01e24-9a15-4ed9-9499-160911dabf74
ORCID for Joy H. Conway: ORCID iD orcid.org/0000-0001-6464-1526
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

Catalogue record

Date deposited: 18 Nov 2020 17:34
Last modified: 22 Nov 2021 08:17

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Contributors

Author: Kerry Day
Author: Kristoffer Ostridge
Author: Joy H. Conway ORCID iD
Author: Doriana Cellura
Author: Alastair Watson
Author: Cosma Mirella Spalluto
Author: Karl J. Staples ORCID iD
Author: Bruce Thompson
Author: Tom Wilkinson

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