Trial Information

Evaluation of Two Minimally Invasive Endoscopic Techniques for the Diagnosis of the Diffuse Lung Diseases.

Diffuse lung disease (DLD) remains a challenging area for diagnosis and treatment. Features
suggestive of the various histological subtypes of DLD can be obtained from the clinical
history and examination, and can also seen on cross-sectional imaging (high resolution
computed tomography (HRCT) scanning), however final diagnosis very often relies on the
results of more invasive testing. The gold-standard diagnostic tool is the surgical lung
biopsy, but this requires a general anaesthetic and either thoracoscopy or thoracotomy. The
morbidity and even mortality attached to this approach in these patients, many of whom have
significant respiratory compromise, has resulted in less invasive techniques being employed
in many instances. At present, this involves the use of bronchoalveolar lavage (BAL) and
transbronchial biopsies via the fibreoptic bronchoscope. BAL can be distressing for
patients if there is spill-over of lavage fluid into the larger airways, and transbronchial
biopsies lead to significant bleeding or pneumothorax in around 5% of patients. Even with
biopsies and BAL, some patients still progress to surgical lung biopsy.

There have recently been developed 2 systems for use via the working channel of the
endoscope which provide imaging of the distal airways and alveoli in vivo and in real time.
These are described below. In principal, these could provide diagnostic information in the
setting of DLD without the need for biopsies or BAL, reducing morbidity and cost associated
with sample processing, and shortening the time to diagnosis. The ideal situation would be
that sufficient morphological and histological information could be obtained using these
systems, thus obviating altogether the need for surgical biopsy in this patient group,
providing further benefits for the patient and potentially huge cost savings for
institutions.

Cellvizio® Lung (Mauna Technology) Confocal microscopy is the standard tool for ultrahigh
resolution imaging in biomedical research. Mauna Technology has developed a 1.4mm diameter
Alveoflex Confocal Miniprobe™ which can be deployed down the working channel of a standard
bronchoscope. Elastin is the main in vivo fluorophore, and images are acquired by gentle
contact, providing microstructural detail of the alveolus on multiple tissue layers.
Because the system takes advantage of the natural fluorescence of the lung tissues, no
patient preparation is required.

Endocytoscope system (ECS) The endocytoscope is a newly developed system that can be passed
through the working channel of a standard bronchoscope, and provides high magnification
views (x450) of cell surfaces. About 5mls of 0.5% methylene blue solution is used to stain
the area of interest, and images are obtained by contact with the cell surface. Use of the
ECS has already been shown to allow discrimination between normal and abnormal tissue in
situ in the setting of bronchial dysplasia and malignancy.

Aim of research The purpose of this research project is to build up a database of
information gathered using both systems so that features correlating with the different
diffuse lung diseases (e.g. sarcoidosis, interstitial pneumonias, drug induced lung
diseases, emphysema) can be recorded. Patients with normal lung parenchyma and focal
disease such as lung cancer will also be evaluated in order to develop a better
understanding of pulmonary morphology using these techniques. By using two potentially
complimentary systems that look at different structural aspects of the target tissues, a
greater understanding of in vivo tissue characteristics can be gained. It is hoped that
diagnostic criteria can then be drawn up for individual diseases that can then be assessed
prospectively in trials.