Chest

Chest

Volume 143, Issue 5, May 2013, Pages 1436-1443
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Translating Basic Research into Clinical Practice
Small Airway Obstruction in COPD: New Insights Based on Micro-CT Imaging and MRI Imaging

https://doi.org/10.1378/chest.12-1766Get rights and content

The increase in total cross-sectional area in the distal airways of the human lung enhances the mixing of each tidal breath with end-expiratory gas volume by slowing bulk flow and increasing gas diffusion. However, this transition also favors the deposition of airborne particulates in this region because they diffuse 600 times slower than gases. Furthermore, the persistent deposition of toxic airborne particulates stimulates a chronic inflammatory immune cell infiltration and tissue repair and remodeling process that increases the resistance in airways <2 mm in diameter four to 40-fold in COPD. This increase was originally attributed to lumen narrowing because it increases resistance in proportion to the change in lumen radius raised to the fourth power. In contrast, removal of one-half the number of tubes arranged in parallel is required to double their resistance, and approximately 90% need to be removed to explain the increase in resistance measured in COPD. However, recent reexamination of this problem based on micro-CT imaging indicates that terminal bronchioles are both narrowed and reduced to 10% of the control values in the centrilobular and 25% in the panlobular emphysematous phenotype of very severe (GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade IV) COPD. These new data indicate that both narrowing and reduction in numbers of terminal bronchioles contribute to the rapid decline in FEV1 that leads to severe airway obstruction in COPD. Moreover, the observation that terminal bronchiolar loss precedes the onset of emphysematous destruction suggests this destruction begins in the very early stages of COPD.

Section snippets

Peripheral Lung Anatomy

The boundary between purely conducting airways and gas-exchanging tissue is formed by the division of approximately 44,510±15,574 (mean±SD) terminal bronchioles into transitional bronchioles or first-order respiratory bronchioles where alveolar openings first appear (Fig 1).8, 9 The alveolar openings steadily increase with successive generations of branching until they occupy the entire luminal surface of alveolar ducts and ducts branch for several more generations before terminating in closed

Peripheral Airways Resistance in Normal Lungs

The older paradigm that the small conducting airways offer the most resistance to airflow in normal human lungs put forward by Rohrer in the 1920s16, 17 began to change in the 1960s when Green repeated Rohrer's calculations using Weibel's new data and found that the smaller airways offered much less resistance than Rohrer's calculations indicated because both the total number and cross-sectional area of the smaller conducting airways were underestimated.11, 16, 17, 18 However, the major shift

Peripheral Airway Resistance in COPD

In contrast to the disagreement concerning the resistance to flow offered by small airways <2 mm in diameter in normal lungs, all three groups that have made direct measurements of small airways resistance in COPD (including the Belgian group) reported that the small conducting airways <2 mm in diameter become the major site of increased resistance in COPD.7, 14, 23

On theoretical grounds, the substantial increase in peripheral airways resistance measured in COPD is easier to explain by

The Sequence of Tissue Destruction in COPD

Figure 4 was constructed from existing data where Figure 4A shows normal terminal bronchioles and Figure 4B shows Leopold and Gough's30 original diagram of a primary centrilobular lesion that develops beyond the terminal bronchiole that was also described by McLean31 at about the same time. Figure 4C shows a fully developed centrilobular lesion outlined by radio-opaque dust in a study that showed these lesions are on the flat part of their pressure volume curve at about 80% of their total gas

Summary

In the normal lung, the increase in total cross-sectional area of the conducting airways with each generation of branching facilitates gas mixing by slowing the bulk flow of gas and increasing its diffusion into the distal airapaces.11, 15 However, this transition also favors the accumulation of airborne particles within this region of the lung because these particles diffuse approximately 600 times slower than gas.15 The accumulation of toxic particles in this lung region stimulates a

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Hogg serves as the principal investigator (PI) or co-investigator of grants to The University of British Columbia from the US National Institutes of Health, Canadian Institutes of Health Research, and the British Columbia Lung Association. Additionally, Dr Hogg serves as the PI on a contract between The University of British Columbia and Boehringer Ingleheim GmbH (BI) and Merck Canada

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    Dr McDonough is currently pursuing postdoctoral studies at Imperial College London, London, England. Dr Suzuki is currently affiliated with Hokkaido University, Saporro, Japan.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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    Copyright © 2013 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.