Airway Structure in Asthma: A Role for Confocal Microscopy?

Goldie, Roy G.; Fernandes, Lynette; Rigby, Paul; Pudney, C.J.; Spalding, Lisa; O’Connor, Brian; Page, C. P.

doi:10.1006/pupt.1999.0161

Cited by 4 publications

(7 citation statements)

References 14 publications

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“…We expect newer image analysis techniques to resolve the widespread conflicts in disease neuroplasticity studies (10)(11)(12)(13)(14)(15)(16), to quantify early subtler changes in nerve architecture that precede changes in overall density (1,9), and to advance studies of neuroplasticity as a therapeutic target (5)(6)(7)(8).…”

Section: Discussionmentioning

confidence: 99%

“…However, morphologically complex nerve architecture, including branching axonal processes and dendritic spines, are undersampled in two-dimensional images. Undersampling likely contributes to opposite findings of hyperinnervation and hypoinnervation in studies of asthma (10)(11)(12), diabetes (13)(14)(15), and inflammatory pain (15,16). Design-based stereology is a newer method to reduce experimental bias (17), but objects with low sampling probability, such as airway epithelial nerve populations, require an impractical amount of sampling to fulfill the American Thoracic Society's stereology requirements for sufficient precision and efficiency (18).…”

mentioning

confidence: 99%

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Quantifying Nerve Architecture in Murine and Human Airways Using Three-Dimensional Computational Mapping

Scott

Fryer

Jacoby

2013

Am J Respir Cell Mol Biol

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The quantitative histological analysis of airway innervation using tissue sections is challenging because of the sparse and patchy distribution of nerves. Here we demonstrate a method using a computational approach to measure airway nerve architecture that will allow for more complete nerve quantification and the measurement of structural peripheral neuroplasticity in lung development and disease. We demonstrate how our computer analysis outperforms manual scoring in quantifying three-dimensional nerve branchpoints and lengths. In murine lungs, we detected airway epithelial nerves that have not been previously identified because of their patchy distribution, and we quantified their three-dimensional morphology using our computer mapping approach. Furthermore, we show the utility of this approach in bronchoscopic forceps biopsies of human airways, as well as the esophagus, colon, and skin.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Quantifying Nerve Architecture in Murine and Human Airways Using Three-Dimensional Computational Mapping

Scott

Fryer

Jacoby

2013

Am J Respir Cell Mol Biol

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“…A complex array of biochemical mediators has been suggested to have a role in airways remodelling; however, much of the evidence for their involvement is circumstantial, rather than definitive. Mediators released by epithelial cells, such as cytokines, growth factors and endothelins, are thought to play an important part in inflammation and also possibly remodelling in asthmatic airways [17,19–22]. For example, endothelins are known to be overproduced in asthmatic airways, and to be able to stimulate proliferation of fibroblasts in culture [22].…”

Section: Aetiology and Mechanismsmentioning

confidence: 99%

“…For example, endothelins are known to be overproduced in asthmatic airways, and to be able to stimulate proliferation of fibroblasts in culture [22]. Endothelin‐1 (ET‐1) is also known to have a potent contractile effect on airway smooth muscle, is synthesized in and released from bronchial epithelial cells, and its release in vitro is increased by pro‐inflammatory stimuli such as thrombin and various cytokines [19]. The growth factors transforming growth factor‐β (TGF‐β) and epidermal growth factor (EGF) can increase DNA synthesis in airway smooth muscle cells in vitro , but their role in causing smooth muscle proliferation in asthmatic lungs is less clear [23].…”

Section: Aetiology and Mechanismsmentioning

confidence: 99%

Airway remodelling in asthma

2002

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Summary Airway remodelling is a relatively new concept in asthma research. It can be defined as the ‘structural changes in the airways that may affect their functional properties’. The structural changes usually comprise smooth muscle hyperplasia, hypertrophy of mucus glands, subepithelial fibrosis, angiogenesis and changes to the extracellular matrix. One of the most important consequences of these changes is narrowing of the airway lumen. The aetiology of remodelling has not been elucidated fully, but it is clear that there is an important association between remodelling and inflammation. However, the degree to which one process causes the other, and the nature of the causality, is not known. Numerous cells and mediators including epithelial cells, cytokines and growth factors all appear to play a part in the remodelling process, but the precise roles of specific cells and mediators are yet to be defined clearly. Because of the problems in assessing the extent of remodelling in living patients, research into the clinical consequences of this process has been difficult. However, it is clear that the extent of remodelling correlates with the severity of asthma, and patients with extensive remodelling may also be resistant to steroid treatment. It is not clear whether remodelling is generally reversible, although there is evidence that it is in some patients, and this reversal is associated with improvement in symptoms. However, remodelling represents an important target for the development of future drugs to treat asthma, and pharmacological treatment that could reverse the process of remodelling has the potential to play a key role in asthma management.

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“…However, lung nerve subpopulations are sparsely and unevenly distributed, and this may explain inconsistent findings in attempting to characterize pulmonary neuroplasticity in disease using traditional histological methods (4)(5)(6). This sampling problem is compounded because the distribution of the disease itself is often patchy (7,8).…”

mentioning

confidence: 99%

Tissue Optical Clearing, Three-Dimensional Imaging, and Computer Morphometry in Whole Mouse Lungs and Human Airways

Scott

Blum

Fryer

et al. 2014

Am J Respir Cell Mol Biol

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In whole adult mouse lung, full identification of airway nerves (or other cellular/subcellular objects) has not been possible due to patchy distribution and micron-scale size. Here we describe a method using tissue clearing to acquire the first complete image of threedimensional (3D) innervation in the lung. We then created a method to pair analysis of nerve (or any other colabeled epitope) images with identification of 3D tissue compartments and airway morphometry by using fluorescent casting and morphometry software (which we designed and are making available as open-source). We then tested our method to quantify a sparse heterogeneous nerve population by examining visceral pleural nerves. Finally, we demonstrate the utility of our method in human tissue to image full thickness innervation in irregular 3D tissue compartments and to quantify sparse objects (intrinsic airway ganglia). Overall, this method can uniquely pair the advantages of whole tissue imaging and cellular/subcellular fluorescence microscopy.

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Airway Structure in Asthma: A Role for Confocal Microscopy?

Cited by 4 publications

References 14 publications

Quantifying Nerve Architecture in Murine and Human Airways Using Three-Dimensional Computational Mapping

Quantifying Nerve Architecture in Murine and Human Airways Using Three-Dimensional Computational Mapping

Airway remodelling in asthma

Tissue Optical Clearing, Three-Dimensional Imaging, and Computer Morphometry in Whole Mouse Lungs and Human Airways

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