Abstract
BackgroundAirway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM) is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by in vitro spectral analysis of elastin powder. We hypothesized that FCFM images capture in vivo elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated.MethodsIn a cross-sectional study comprising 16 subjects (8 atopic asthmatic patients with controlled disease and 8 healthy controls) spirometry and bronchoscopy were performed, with recording of FCFM images followed by endobronchial biopsy at the airway main carina. Elastic fibre patterns in histological sections and FCFM images were scored semi-quantitatively. Agreement between histology and FCFM was analysed using linearly weighted kappa κw.ResultsThe patterns observed in histological sections and FCFM images could be divided into 3 distinct groups. There was good agreement between elastic fibre patterns in histology and FCFM patterns (κw 0.744). The semi-quantitative pattern scores were not different between asthmatic patients and controls. Notably, there was a significant difference in post-bronchodilator FEV1 %predicted between the different patterns by histology (p = 0.001) and FCFM (p = 0.048), regardless of asthma or atopy.ConclusionFCFM captures the elastic fibre pattern within the airway wall in humans in vivo. The association between post-bronchodilator FEV1 %predicted and both histological and FCFM elastic fibre patterns points towards a structure-function relationship between extracellular matrix in the airway wall and lung function.Trial registrationNetherlands Trial Register NTR1306
Highlights
Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall
The present study shows that elastic fibres in the airway wall can be visualized by Fibered confocal fluorescence microscopy (FCFM), a novel bronchoscopic imaging modality, and that a laminar pattern of these fibres is associated with reduced lung function
The present results suggest that FCFM is an adequate method to examine bronchial elastic fibre morphology in vivo and might be an important tool to detect asthmatic patients who are prone to loss of lung function, at an early stage enabling timely intervention
Summary
Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM) is a new imaging modality, representing a non-invasive method that can be used to image the microscopic structure of airway wall tissue in vivo during a bronchoscopic procedure [13]. The principle of this imaging method is based on the autofluorescence of endogenous or exogenous fluorophores inside the tissues after excitation by an external laser light source. High-quality and real-time in vivo morphological images or ‘optical biopsies’ of the airway wall are obtained by placing the tip of the miniprobe onto the airway wall surface. Another advantage of FCFM and its miniprobe is the ability to reach and visualize the alveoli in vivo [15]
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