title: In vivo imaging of the airway wall in asthma: fibered confocal fluorescence microscopy in relation to histology and lung function.
abstract: BACKGROUND
  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 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  FCFM 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.
  
  
  BACKGROUND
  Netherlands Trial Register NTR1306.
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, Amsterdam, The Netherlands. C.Y.Yick@amc.uva.nl
authors.forename: Ching Yong
authors.initials: CY
authors.lastname: Yick
authors.forename: Jan H
authors.initials: JH
authors.lastname: von der Thüsen
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Bel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kunst
mesh_terms: D000293:Adolescent; D000328:Adult; D056151:Airway Remodeling; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D001706:Biopsy; D001999:Bronchoscopy; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D004547:Elastic Tissue / Q000473:pathology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009426:Netherlands; D011237:Predictive Value of Tests; D013147:Spirometry; D014797:Vital Capacity; D055815:Young Adult