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Small airways occurs in mild and moderate Chronic Obstructive Pulmonary Disease: a cross-sectional study

Small airways occurs in mild and moderate Chronic Obstructive Pulmonary Disease: a cross-sectional study
Small airways occurs in mild and moderate Chronic Obstructive Pulmonary Disease: a cross-sectional study
Background: the concept that the small conducting airways <2mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the literature. It has also been shown that the last generation of small conducting airways, terminal bronchioles, are significantly destroyed in patients with very-severe COPD. What is not known is at what stage in the development of COPD the loss of small airways occurs, or how loss of terminal and transitional (first generation of respiratory airways) bronchioles - relates to the loss alveolar surface area that characterizes emphysema. 

Methods: a novel multi-resolution computed tomography (CT) imaging protocol was applied to systematically, randomly sampled whole lungs or lobes of smokers with normal lung function (n=10), mild (n=10), moderate (n=8), and very-severe COPD (n=6). The 34 lung specimens provided 262 lung tissue samples for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (Lm), alveolar surface area. 

Findings: the new data demonstrate that 41% of terminal bronchioles, 57% of transitional bronchioles, and 37% of the alveolar surface area is lost in patients with mild and moderate COPD compared to control smokers, before any emphysematous changes can be detected by CT. We also show these pathological changes correlate with lung function decline. Importantly, we demonstrate that loss of terminal and transitional bronchioles occurs in regions of the lung that have no loss of alveolar surface area. Further, we validated using histology, that the surviving small airways have thickened walls and narrowed lumens which become more obstructed as the disease progresses. 

Interpretation: these data demonstrate that small airways disease is an early pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention in mild and moderate COPD patients is most likely required for disease modification.
COPD, Small Airway Disease, Emphysema, COPD Pathology
2213-2600
591-602
Koo, Hyun-Kyoung
4b7ef96d-88cb-4c04-a85c-0eefb9e0d3ec
Vasilescu, Dragos M.
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Booth, Steven
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Hsieh, Aileen
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Katsamenis, Orestis L.
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Fishbane, Nick
c1635691-42ab-451b-9cae-1fcda52978ce
Elliott, W. Mark
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Kirby, Miranda
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Lackie, Peter
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Sinclair, Ian
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Warner, Jane A.
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Cooper, Joel D.
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Coxson, Harvey O.
42f20a11-e52f-47aa-b1d1-59bac89fa580
Pare, Peter D.
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Hogg, James C.
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Hackett, Tillie-Louise
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Koo, Hyun-Kyoung
4b7ef96d-88cb-4c04-a85c-0eefb9e0d3ec
Vasilescu, Dragos M.
a2195697-7b50-4701-82c1-b700e4e8331c
Booth, Steven
c2026d9d-ed93-4b1b-bce5-6b3efc8b8ca5
Hsieh, Aileen
0b12d017-2802-4ef3-81a1-333105d656b5
Katsamenis, Orestis L.
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Fishbane, Nick
c1635691-42ab-451b-9cae-1fcda52978ce
Elliott, W. Mark
93b6c5f2-2a42-4f14-80a2-d0a6909ecc9e
Kirby, Miranda
727ec951-7577-4905-9a83-9fffe1b2e304
Lackie, Peter
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a
Sinclair, Ian
6005f6c1-f478-434e-a52d-d310c18ade0d
Warner, Jane A.
8571b049-31bb-4a2a-a3c7-4184be20fe25
Cooper, Joel D.
9f6d1334-7e72-47ba-9ac2-928911f3b912
Coxson, Harvey O.
42f20a11-e52f-47aa-b1d1-59bac89fa580
Pare, Peter D.
7592c7e5-7042-4e0c-9d97-94ee3b3cf745
Hogg, James C.
69089b38-86b4-46d9-a5fc-610a13142ad9
Hackett, Tillie-Louise
05158d38-5bd8-4cce-9c82-5f86ab8f2757

Koo, Hyun-Kyoung, Vasilescu, Dragos M., Booth, Steven, Hsieh, Aileen, Katsamenis, Orestis L., Fishbane, Nick, Elliott, W. Mark, Kirby, Miranda, Lackie, Peter, Sinclair, Ian, Warner, Jane A., Cooper, Joel D., Coxson, Harvey O., Pare, Peter D., Hogg, James C. and Hackett, Tillie-Louise (2018) Small airways occurs in mild and moderate Chronic Obstructive Pulmonary Disease: a cross-sectional study. The Lancet Respiratory Medicine, 6 (8), 591-602. (doi:10.1016/S2213-2600(18)30196-6).

Record type: Article

Abstract

Background: the concept that the small conducting airways <2mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the literature. It has also been shown that the last generation of small conducting airways, terminal bronchioles, are significantly destroyed in patients with very-severe COPD. What is not known is at what stage in the development of COPD the loss of small airways occurs, or how loss of terminal and transitional (first generation of respiratory airways) bronchioles - relates to the loss alveolar surface area that characterizes emphysema. 

Methods: a novel multi-resolution computed tomography (CT) imaging protocol was applied to systematically, randomly sampled whole lungs or lobes of smokers with normal lung function (n=10), mild (n=10), moderate (n=8), and very-severe COPD (n=6). The 34 lung specimens provided 262 lung tissue samples for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (Lm), alveolar surface area. 

Findings: the new data demonstrate that 41% of terminal bronchioles, 57% of transitional bronchioles, and 37% of the alveolar surface area is lost in patients with mild and moderate COPD compared to control smokers, before any emphysematous changes can be detected by CT. We also show these pathological changes correlate with lung function decline. Importantly, we demonstrate that loss of terminal and transitional bronchioles occurs in regions of the lung that have no loss of alveolar surface area. Further, we validated using histology, that the surviving small airways have thickened walls and narrowed lumens which become more obstructed as the disease progresses. 

Interpretation: these data demonstrate that small airways disease is an early pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention in mild and moderate COPD patients is most likely required for disease modification.

Text THELANCETRM-D-18-00172R1_clean - Accepted Manuscript
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More information

Accepted/In Press date: 30 April 2018
e-pub ahead of print date: 4 July 2018
Published date: August 2018
Keywords: COPD, Small Airway Disease, Emphysema, COPD Pathology

Identifiers

Local EPrints ID: 421702
URI: https://eprints.soton.ac.uk/id/eprint/421702
ISSN: 2213-2600
PURE UUID: 60eebea0-3382-44c2-b500-2e1c9b61bb9a
ORCID for Orestis L. Katsamenis: ORCID iD orcid.org/0000-0003-4367-4147
ORCID for Peter Lackie: ORCID iD orcid.org/0000-0001-7138-3764

Catalogue record

Date deposited: 21 Jun 2018 16:30
Last modified: 06 Oct 2018 00:39

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