CLE and OCT in diagnosing ILD, a comparison with imaging and pathology.

Interstitial lung disease (ILD), refers to a group of lung diseases affecting
the interstitium, causing stiffness of the lungs and impaired gas exchange due
to inflammation and changes in the extra-cellular matrix composition of the
alveolar septae. Often, assessing a classifying diagnosis provides a
diagnostic challenge. Currently HRCT, endoscopic or surgical (VATS) assessment
including lung biopsies are diagnostic tools for patients with suspected ILD.
However, tissue acquisition is associated with morbidity in these patients with
an already compromised pulmonary function. The aim of the study is to examine
whether the addition of novel optical techniques to the diagnostic process of
ILD can limit the need for a tissue (surgical) diagnosis and reduce the
sampling error rate of biopsies by providing additional information on biopsy
location.

Novel probe based optical techniques such as Confocal laser endomicroscopy
(pCLE) and Optical coherence tomography (pOCT) are non-invasive optical
techniques, compatible with conventional diagnostic bronchoscopes and provide
non-invasive, real-time information on the airway wall and the alveolar
compartment. Therefore, immediate validation of optical measurements during a
biopsy is possible. Optical techniques might either obviate the need for an
tissue biopsy or improve the diagnostic yield of conventional biopsy methods
and make surgical lung biopsies that are associated with high morbidity and
costs redundant.

To identify and define characteristics of ILD on the pCLE and pOCT image of
airway wall mucosa and the alveolar compartment and compare this to HRCT
imaging and pathology.

This is an investigator-initiated, observational study in 20 ILD patients. For
this study we conduct pCLE and pOCT imaging of the alveolar compartment of ILD
patients with an indication for cryobiopsy. In patients who have an additional
indication for biopsies of the airway wall mucosa (EBB), we will also conduct
pCLE and pOCT imaging of the airway wall mucosa. Before the bronchoscopic
procedure an exploratory breathprint will be obtained by electronic nose for
the purpose of building a breathcloud. This will be recorded and processed by
R. de Vries. according to the study: de Vries et al, 'Integration of
Electronic Nose Technology with Spirometry: Validation of a New Approach for
exhaled Breath Analysis', currently revised for Journal of Breath Research.

A participating patient will not benefit from this study. However the results
of this study may benefit the diagnostic procedure of future ILD diagnostics
and may improve quality of life of future ILD patients. The procedure of
bronchoscopy combined with the novel non-invasive, probe based, optical
techniques in the airways and the alveolar compartment have proved to be safe
and provide real time information on a microscopic level regarding tissue
architecture. There is little burden related to study participation: during the
conventional bronchoscopic procedure, optical pCLE and pOCT measurements with
the use of a light beam will be performed by holding the probe in perpendicular
contact with the tissue, followed by conventional cryobiopsy and/or EBB
(routine work up) at the same site as the CLE/ OCT measurements, without the
need for additional biopsies for research purposes. Estimated prolonged
bronchoscopy time due to imaging is 5 to 10 minutes. The patient will not
notice anything due to the use of propofol sedation (part of standard
protocol). Adverse advents are not expected, based on our own OCT experience in
the TASMA trial (asthma patients), and the data of previous studies where
bronchoscopy combined with probe based optical techniques are reported to be
safe, easy to perform and little time-consuming, without adverse events. In
conclusion, in our opinion the burden and risks associated with the additional
probe based optical technique measurements are neglectible.