Fibered Confocal Fluorescence Microscopy Imaging in Patients With Diffuse Parenchymal Lung Diseases
Fibered Confocal Fluorescence Microscopy Imaging in Patients With Diffuse Parenchymal Lung Diseases
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.
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.
Inclusion Criteria:

 1. Patients 21 years old and older diagnosed with suspected diffuse parenchymal lung
 disease (multi-lobar pulmonary infiltrates)

 2. Patients scheduled for bronchoscopy as part of regular clinical care/diagnostic workup

 3. Ability and willingness to sign informed consent

 Exclusion Criteria:

 1. Contraindications to bronchoscopic evaluation eg. Haemodynamic instability,
 respiratory failure, uncorrected coagulopathy

 2. Suspected/confirmed pregnancy