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Review
. 2019 Mar 4;20(1):49.
doi: 10.1186/s12931-019-1017-y.

The pathology of small airways disease in COPD: historical aspects and future directions

Andrew Higham  1 , Anne Marie Quinn  2 , José Eduardo D Cançado  3 , Dave Singh  4   5
Affiliations
Review

The pathology of small airways disease in COPD: historical aspects and future directions

Andrew Higham et al. Respir Res. .

Abstract

Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathological changes are not complete. In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation. We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations. We discuss the need to specifically target SAD to attenuate the progression of COPD.

Keywords: Bacteria; COPD; Emphysema; Exacerbations; Histopathology; Inflammation; Remodeling; Small airways disease.

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Conflict of interest statement

Ethics approval and consent to participate

Tissue used to produce images in this review was taken from patients undergoing surgical resection for suspected lung cancer. All subjects gave written informed consent and this research was approved by the NRES Committee North West-Greater Manchester South (reference 03/SM/396).

Competing interests

AH has no competing interests. AMQ has received honoraria for lecturing for AstraZeneca and Roche and has acted as an advisor for Diaceutics Limited. DS has received sponsorship to attend international meetings, honoraria for lecturing or attending advisory boards and research grants from various pharmaceutical companies including Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, GlaxoSmithKline, Glenmark, Johnson and Johnson, Merck, NAPP, Novartis, Pfizer, Skypharma, Takeda, Teva, Therevance and Verona. JEDC has received sponsorship to attend international meetings, honoraria for lecturing or attending advisory boards from various pharmaceutical companies including Aché, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Pfizer.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Transitioning epithelial structure in a respiratory bronchiole. a A bronchiole demonstrating transition from the columnar epithelium to cuboidal epithelium and finally to flattened alveolar epithelium (2X magnification). b An enlarged image of the inset from image A showing columnar epithelium (black arrow), cuboidal epithelium (green arrow) and flattened epithelium (red arrow) (10X magnification). Section stained with hematoxylin and eosin
Fig. 2
Fig. 2
Histopathological features of small airways disease in COPD. a A COPD bronchiole with a thickened airway wall due to fibrotic remodeling and excessive deposition of collagen bundles (blue colouration). Section stained with Masson’s Trichrome (10X magnification). b A COPD bronchiolevascular bundle whereby the bronchiole contains a large intra-luminal mucous plug (red arrow) (2X magnification). Section stained with hematoxylin and eosin. c A COPD bronchiole with increased numbers of goblet cells (greenarrows) in the epithelial lining (20X magnification). Section stained with hematoxylin and eosin. d The wall of a COPD bronchiole with increased numbers of inflammatory cells (black arrows) (20X magnification). Section stained with hematoxylin and eosin
Fig. 3
Fig. 3
Smoking associated centrilobular emphysema. a An area of emphysematous lung with severe effacement of alveolar walls (4X magnification). b Normal lung with intact alveolar walls (4X magnification). Sections stained with hematoxylin and eosin
Fig. 4
Fig. 4
The mechanism of small airways disease onset and progression in COPD. Cigarette smoking causes injury to the small airways. In response, aberrant repair processes result in excessive airway remodelling, mucous plugging and immune cell infiltration. These contribute to the onset and progression of small airways disease, which precedes emphysema. These changes may lead to increased COPD exacerbations and bacterial colonization, which, in turn, may contribute to small airways disease progression and emphysema development
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References

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MeSH terms