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COPD – respiratory diseases – Small airway remodeling

The current literature on small airway remodeling (SAR) stresses the need for a fully automated quantitative analysis that could lead to fast, accurate, reliable and independent-observer assessment of airway morphological changes.

BIOCELLVIA’S SMALL AIRWAY REMODELING ASSAY

To achieve successfully the automatic quantitative analysis of SAR Biocellvia developed a proprietary numerical analysis allowing the assessment of multiple key morphometric parameters leading to a reliable, accurate, very fast and reproducible evaluation of changes occurring in pulmonary small airways (figure 1). Quantification of morphometric parameters can be coupled to the automatic quantification of peribronchial collagen as well as target immunostainings (figure 2).

Fig 1 SAR

Figure 1. Representative image of a small bronchiole selected automatically from an entire lung section non-exposed to cigarette smoke. Original numerical lung section, stained with HE, was obtained from the histological slide scanning. The selection of small bronchiole with a part of parenchymal tissue was followed by the automatic delineation of its external and internal limits. These delineations allowed to assess multiple key morphometric parameters which were then automatically transferred in Excel table for their statistical analysis.

Fig2 SAR

Figure 2. Representative image of a small bronchiole stained with sirius red of a mouse lung non-exposed to cigarette smoke. The discrimination of sirius red from the original image was followed by a discrimination of peribronchial sirius red (collagen). Morphometric parameters and related percentage of peribronchial collagen of the small bronchiole were then transferred in an Excel table for statistical analysis.

SMALL AIRWAY MORPHOMETRIC PARAMETERS

  • Bronchi area, corresponding to the area (µm2) of the bronchi delimited by the outer limit of the bronchial wall.
  • Lumen area, corresponding to the area (µm2) of the bronchi delimited by the inner limit of the bronchial wall.
  • Wall area, corresponding to the difference between the total bronchi area and the lumen area (µm2).
  • Wall thickness, measured from the difference between the radius of the outer and the inner limits of the bronchi. The wall thickness is evaluated from several hundreds of radius originated from the mass center of the bronchi.

TOTALLY AUTOMATED ANALYSIS OF SMALL AIRWAY REMODELING

The extent of small airway remodeling can be assessed accurately by quantifying changes of small bronchi morphometric parameters. As an example taken from the mouse model exposed to cigarette smoke morphometric changes were characterized by a significant increase of total area, lumen, wall area and thickness of small bronchi coupled to a significant increase of peribronchial collagen (figure 3).

All these morphometric parameters are acquired automatically in a very short time (<30 sec/entire lung section) and independently of the observer.

Fig 3

Figure 3. Quantification of small airways remodeling in lung of cigarette smoke-exposed mouse model. A comparison was established between air-exposed and cigarette smoke-exposed (4 weeks) lungs. Cigarette smoke induced in small bronchi a statistically significant increase of bronchi area (+71%), lumen area (+85%) and wall area (+46%) associated with a statistically significant increase of the peribronchial collagen (+103%). *p<0.05, **p<0.01, ***p<0.001.

The implementation of multiple key morphometric parameters of small bronchi coupled to collagen and target biomarkers provides new fundamental data which contribute to a better and deeper analysis of SAR in COPD animal models. This new approach supplies a total reliability and reproductibility for preclinical drug evaluation and consequently a robust support for decision-making.

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