Fibered Confocal Fluorescence Microscopy Imaging in Patients With Diffuse Parenchymal Lung Diseases
Condition: Diffuse Parenchymal Lung Diseases
MeSH terms: Lung Diseases; Lung Diseases, Interstitial
Study type: Interventional

Summary: 
      Fibered confocal fluorescence microscopy (FCFM) (CellvizioR Lung, MaunaKea Technologies,
      France) could potentially provide diagnostic information on fibrosis and inflammation of the
      distal air spaces associated with diffuse parenchymal lung diseases without the need for lung
      biopsies, thereby fulfilling the gap in the investigators current medical practice of a
      minimally invasive procedures with few complications and a high diagnostic fidelity.

      In patients scheduled for bronchoscopy as part of regular clinical care/diagnostic workup,
      the investigators will offer the patient concurrent FCFM imaging to be performed during the
      bronchoscopic procedure. The investigators aim to identify and catalogue distinct and
      discriminating features seen on images obtained from fibered confocal fluorescence microscopy
      in this group of patients, and to correlate these findings with specific high resolution
      computed tomography (HRCT) features and pathological findings if available. Eventually the
      investigators hope to create diagnostic criteria for fibered confocal fluorescence microscopy
      image interpretation of specific diffuse parenchymal lung disease entities.
    

Detailed description: 
      Diffuse parenchymal lung diseases (DPLD) represent a large and heterogeneous group of
      disorders encompassing a collection of pulmonary diseases that affect the interstitium
      including the alveolar epithelium, pulmonary capillary endothelium, basement membrane,
      perivascular and perilymphatic tissues. This spectrum of disease is encountered not only in
      pulmonary medicine as a collection of idiopathic conditions, but also in transplant medicine
      (solid organ and haematological), infectious disease (atypical pneumonias) and rheumatology
      (connective tissue disease/vasculitis). Although new techniques such as high resolution
      computed tomography (HRCT) and insights into the pathogenesis have led to a better
      understanding of DPLD, clinical diagnosis, management and prognostication remains a
      challenge.

      The current diagnostic standard of DPLD is a correlation between clinical course,
      radiological features on HRCT and pathological findings. Even in idiopathic pulmonary
      fibrosis (IPF) where a typical usual interstitial pattern on HRCT is pathognomonic without
      the requirement of pathology, this is only diagnostic in 80% of patients, and an atypical
      pattern on HRCT does not preclude a diagnosis of IPF. As such the final diagnosis often
      hinges on histopathological confirmation which traditionally requires a surgical lung biopsy
      under general anaesthetic via thoracoscopy or thoracotomy. This entails significant morbidity
      and mortality in this group of patients who already have respiratory compromise. Minimally
      invasive endoscopic procedures such as bronchoalveolar lavage (BAL) and transbronchial lung
      biopsy (TBLB) via flexible bronchoscopy have increasingly been used in the majority of cases
      as a substitute to surgical biopsy. This unfortunately is not entirely a benign procedure
      either - BAL can worsen hypoxaemia, and TBLB may lead to significant bleeding or pneumothorax
      in around 5% of patients. Furthermore, the diagnostic yield of TBLB is severely limited
      because of the small size of tissue and the blind nature of choosing target bronchopulmonary
      segments to biopsy. Other limitations include significant inter-observer variation in
      interpretation of the histology, and the problem of ''sampling error'': the possibility that
      a biopsy specimen was taken from an area not representative of the predominant disease
      process. These limitations are reflected in the low diagnostic yields reported - in
      immunocompromised patients, the diagnostic yield of either BAL or TBLB was 38% with a 13%
      complication rate, and diagnostic yields of <50% with TBLB have been reported in
      hypersensitivity pneumonitis and about 30% in usual interstitial pneumonia.

      A definitive diagnosis is essential in the management of diffuse parenchymal lung diseases.
      Infectious aetiologies necessitate antimicrobial therapy while immune mediated causes are
      managed by immunosuppression. Drug induced pathology will require a revision of current
      medication while fibrotic conditions can be managed expectantly. Prognostication is also
      markedly altered by aetiology and diagnosis. The gap in current medical practice is the
      availability of minimally invasive procedures with few complications and a high diagnostic
      fidelity.

      Fibered confocal fluorescence microscopy (FCFM) (CellvizioR Lung, MaunaKea Technologies,
      France) is a new, safe and minimally invasive technique that can be used to obtain real time
      high-resolution, microstructural images of lobular and alveolar lung structures in living
      humans. FCFM provides a clear, in-focus image of a thin section within a biological sample,
      where the microscope's objective is replaced by a flexible fiberoptic miniprobe. The
      technique makes it possible to obtain high-quality images from endogenous or exogenous tissue
      fluorophores, through a fiberoptic probe of 1.4mm diameter that can be introduced into the
      working channel of a standard, flexible bronchoscope. This could potentially provide
      diagnostic information on fibrosis and inflammation of the distal air spaces associated with
      diffuse parenchymal lung diseases without the need for lung biopsies.

      Current data and imaging for pulmonary FCFM is available in normal alveoli of both smokers
      and non-smokers. Pathological lung FCFM imaging for DPLD has yet to be published. In patients
      scheduled for bronchoscopy as part of regular clinical care/diagnostic workup, the
      investigators will offer the patient concurrent fibered confocal fluorescence microscopy
      imaging to be performed during the bronchoscopic procedure. The investigators aim to identify
      and catalogue distinct and discriminating features seen on images obtained from FCFM in this
      group of patients, and to correlate these findings with specific HRCT features and
      pathological findings if available. The investigators hope to be able to demonstrate
      reproducibility of FCFM image interpretation, with minimal intra and inter observer
      variability and high Kappa values. Eventually the investigators hope to define diagnostic
      criteria and patterns for FCFM image interpretation to correlate with specific DPLD entities,
      thereby creating an atlas of FCFM for DPLD. This would enhance our current diagnosis and
      management of DPLD with minimal additional risks to the patients.
    

Intervention name(s): confocal microscopy
Intervention type(s): Device
Intervention description(s): During bronchoscopy, one side of the bronchial tree will be examined (either right or left) and targeted based on pre-procedure HRCT/CT scan findings. A 1.4mm diameter Alveoflex Confocal MiniprobeTM (MaunaKea Technologies, France) will be deployed down the working channel of the standard bronchoscope and advanced distally into the alveoli. Images are acquired by gentle contact providing real-time imaging and microstructural detail of the alveolus which will be continuously recorded during the procedure and stored for further morphometric and cellular analyses. Up to 10 bronchoalveolar areas will be observed and the location of the corresponding lung segment will be registered according to the international bronchial nomenclature.
Other intervention name(s): Fibered confocal fluorescence microscopy imaging; alveoloscopy; Alveoflex Confocal MiniprobeTM
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: interstitial lung disease; interstitial pneumonia; idiopathic pulmonary fibrosis