The University of Southampton
University of Southampton Institutional Repository

Investigating the nature of small airways disease in mild/moderate COPD: micro-CT analysis of paraffin embedded lung tissue

Investigating the nature of small airways disease in mild/moderate COPD: micro-CT analysis of paraffin embedded lung tissue
Investigating the nature of small airways disease in mild/moderate COPD: micro-CT analysis of paraffin embedded lung tissue
Rationale: Airflow obstruction, the hallmark characteristic of Chronic Obstructive Pulmonary Disease (COPD) has long been attributed to a combination of small airways disease and emphysematous destruction, however, the relative role of each pathological feature is not well understood. McDonough et al. (NEJM, 2011), reported a significant reduction in terminal bronchiolar number in end-stage COPD compared to controls with normal lung function. Further, the study reported that the loss of terminal bronchioles occurred in regions of lung with and without emphysema, leading to our hypothesis that ‘The obstruction and obliteration of small airways occurs early in mild/moderate COPD and precedes the emphysematous destruction’. Methods: Lung samples were obtained from patients with known pulmonary function undergoing surgical resection for lung cancer or transplant. Lungs were inflated, sliced and sampled prior to formalin fixation and paraffin embedding (FFPE). Eight FFPE cores per patient were randomly sampled throughout the lung and scanned using a Nikon Metrology micro-CT scanner. Volumetric data sets were examined to determine mean linear intercept (Lm), number of terminal (TB) and transitional (TrB) bronchioles per ml of tissue. Image registration was used to precisely locate regions of interest, enabling efficient sectioning and staining with Movat’s Pentachrome for a more comprehensive analysis of airway morphology. Results: Our study demonstrates that micro-CT scans of FFPE cores provide adequate resolution of fine lung architecture when compared to mean linear intercept measurements obtained from matched histological sections (Bland-Altman). We report that the total number of terminal bronchioles is significantly decreased from 6.2±1.1 TB/ml in smokers with normal lung function, to 4.6±1.0 TB/ml in mild/moderate COPD patients and 2.8±1.8 TB/ml in severe COPD. Further, we demonstrate a significant decrease in transitional bronchiolar number from 16.7 ± 7.2 TrB/ml in the control group to 10.0 ± 6.0 TrB/ml in mild/moderate COPD, and 2.1±2.7 TrB/ml in severe COPD. When correlating the number of terminal and transitional bronchioles to Lm, we find that bronchioles are destroyed in tissues where no emphysema is present. Lesions of interest are characterized by histology to further understand the pathological process. Conclusions: Clinical trials and the treatment of COPD have traditionally focused on patients with severe disease and no current pharmacological therapies have been shown to affect long term, lung function decline. Our findings suggest that irreversible pathological events occur in the early stages of disease, emphasizing the importance of early diagnosis and intervention to modify the progression of this debilitating respiratory disorder.
1073-449X
Koo, H. -K.
780ead3a-852b-4c9d-9b60-4a65f59d2ed2
Vasilescu, D. M.
a2195697-7b50-4701-82c1-b700e4e8331c
Booth, S.
c2026d9d-ed93-4b1b-bce5-6b3efc8b8ca5
Scott, A. E.
2671ad6e-8e20-486e-af7b-d07abe33c9c0
Katsamenis, O.
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Warner, J.
bc2e44c6-7e76-4336-a4ad-e31434fb4c26
Sinclair, I.
6005f6c1-f478-434e-a52d-d310c18ade0d
Hogg, J. C.
69089b38-86b4-46d9-a5fc-610a13142ad9
Hackett, T. -L.
d4f11c21-f4e5-4366-b393-6670002b66e4
Koo, H. -K.
780ead3a-852b-4c9d-9b60-4a65f59d2ed2
Vasilescu, D. M.
a2195697-7b50-4701-82c1-b700e4e8331c
Booth, S.
c2026d9d-ed93-4b1b-bce5-6b3efc8b8ca5
Scott, A. E.
2671ad6e-8e20-486e-af7b-d07abe33c9c0
Katsamenis, O.
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Warner, J.
bc2e44c6-7e76-4336-a4ad-e31434fb4c26
Sinclair, I.
6005f6c1-f478-434e-a52d-d310c18ade0d
Hogg, J. C.
69089b38-86b4-46d9-a5fc-610a13142ad9
Hackett, T. -L.
d4f11c21-f4e5-4366-b393-6670002b66e4

Koo, H. -K., Vasilescu, D. M., Booth, S., Scott, A. E., Katsamenis, O., Warner, J., Sinclair, I., Hogg, J. C. and Hackett, T. -L. (2016) Investigating the nature of small airways disease in mild/moderate COPD: micro-CT analysis of paraffin embedded lung tissue. American Journal of Respiratory and Critical Care Medicine, 193.

Record type: Article

Abstract

Rationale: Airflow obstruction, the hallmark characteristic of Chronic Obstructive Pulmonary Disease (COPD) has long been attributed to a combination of small airways disease and emphysematous destruction, however, the relative role of each pathological feature is not well understood. McDonough et al. (NEJM, 2011), reported a significant reduction in terminal bronchiolar number in end-stage COPD compared to controls with normal lung function. Further, the study reported that the loss of terminal bronchioles occurred in regions of lung with and without emphysema, leading to our hypothesis that ‘The obstruction and obliteration of small airways occurs early in mild/moderate COPD and precedes the emphysematous destruction’. Methods: Lung samples were obtained from patients with known pulmonary function undergoing surgical resection for lung cancer or transplant. Lungs were inflated, sliced and sampled prior to formalin fixation and paraffin embedding (FFPE). Eight FFPE cores per patient were randomly sampled throughout the lung and scanned using a Nikon Metrology micro-CT scanner. Volumetric data sets were examined to determine mean linear intercept (Lm), number of terminal (TB) and transitional (TrB) bronchioles per ml of tissue. Image registration was used to precisely locate regions of interest, enabling efficient sectioning and staining with Movat’s Pentachrome for a more comprehensive analysis of airway morphology. Results: Our study demonstrates that micro-CT scans of FFPE cores provide adequate resolution of fine lung architecture when compared to mean linear intercept measurements obtained from matched histological sections (Bland-Altman). We report that the total number of terminal bronchioles is significantly decreased from 6.2±1.1 TB/ml in smokers with normal lung function, to 4.6±1.0 TB/ml in mild/moderate COPD patients and 2.8±1.8 TB/ml in severe COPD. Further, we demonstrate a significant decrease in transitional bronchiolar number from 16.7 ± 7.2 TrB/ml in the control group to 10.0 ± 6.0 TrB/ml in mild/moderate COPD, and 2.1±2.7 TrB/ml in severe COPD. When correlating the number of terminal and transitional bronchioles to Lm, we find that bronchioles are destroyed in tissues where no emphysema is present. Lesions of interest are characterized by histology to further understand the pathological process. Conclusions: Clinical trials and the treatment of COPD have traditionally focused on patients with severe disease and no current pharmacological therapies have been shown to affect long term, lung function decline. Our findings suggest that irreversible pathological events occur in the early stages of disease, emphasizing the importance of early diagnosis and intervention to modify the progression of this debilitating respiratory disorder.

Full text not available from this repository.

More information

Published date: 13 May 2016
Additional Information: International Conference of the American-Thoracic-Society (ATS), San Francisco, CA, MAY 13-18, 2016

Identifiers

Local EPrints ID: 412832
URI: http://eprints.soton.ac.uk/id/eprint/412832
ISSN: 1073-449X
PURE UUID: 275fc948-f841-4b66-8019-1ca88830c50d
ORCID for O. Katsamenis: ORCID iD orcid.org/0000-0003-4367-4147

Catalogue record

Date deposited: 02 Aug 2017 16:30
Last modified: 13 Apr 2021 01:45

Export record

Contributors

Author: H. -K. Koo
Author: D. M. Vasilescu
Author: S. Booth
Author: A. E. Scott
Author: O. Katsamenis ORCID iD
Author: J. Warner
Author: I. Sinclair
Author: J. C. Hogg
Author: T. -L. Hackett

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×