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

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 SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation?

STUDY DESIGN AND METHODS: Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n = 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n = 22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions.

RESULTS: Sacin was significantly higher in the COPD FE group compared with the IFE group (P = .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, ρ = 0.560), residual volume to total lung capacity ratio (P = .004, r = 0.730), and the mean lung density of the paired CT scans (P = .018, r = 0.639).

INTERPRETATION: Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.

COPD, exacerbation, inflammation, small airways
0012-3692
1391-1399
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
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), 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 SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation?

STUDY DESIGN AND METHODS: Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n = 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n = 22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions.

RESULTS: Sacin was significantly higher in the COPD FE group compared with the IFE group (P = .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, ρ = 0.560), residual volume to total lung capacity ratio (P = .004, r = 0.730), and the mean lung density of the paired CT scans (P = .018, r = 0.639).

INTERPRETATION: Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.

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More information

e-pub ahead of print date: 25 November 2020
Published date: April 2021
Keywords: COPD, exacerbation, inflammation, small airways

Identifiers

Local EPrints ID: 449220
URI: http://eprints.soton.ac.uk/id/eprint/449220
ISSN: 0012-3692
PURE UUID: 6e157bca-0e70-4f24-a676-327782f05d6b
ORCID for Joy 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: 19 May 2021 18:20
Last modified: 26 Nov 2021 02:51

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Contributors

Author: Kerry Day
Author: Kristoffer Ostridge
Author: Joy 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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