CrYobiopsy With Radial UltraSound Guidance

Diffuse parenchymal lung diseases comprise a group of noninfectious, non-neoplastic lung
diseases, each characterized by varying degrees of inflammation or fibrosis of the parenchyma
of both lungs. The differentiation of these disorders may require biopsy material,
particularly in patients with atypical clinical or radiological presentations. Cryobiopsies
offer specialists the advantage of being able to collect much larger specimens than can be
collected with forceps biopsy, while preserving the underlying lung architecture (no crush
artifact). The biggest disadvantage of cryobiopsy is a higher risk of procedural bleeding
and, to a lesser extent, pneumothorax than conventional transbronchial lung biopsies.

Existing cryobiopsy literature is significantly limited by lack of procedure standardization,
variable diagnostic endpoints and non-uniform grading of complications. Surgical lung biopsy,
currently the gold standard for histological diagnosis of DPLD, is associated with
significant morbidity and mortality. The rate of in-hospital mortality following SLB for DPLD
was recently found to be 1.7% in a large dataset, with a complication rate of 30% (including
post-operative pneumothorax, pneumonia, respiratory failure). Mortality was slightly lower at
1.5% for elective operations but markedly higher at 16% for operations labeled
"non-elective," presumably performed in the setting of acute disease exacerbations. Clearly,
less invasive strategies, such as cryobiopsy, are urgently needed.

Recent studies demonstrate that there might be a trend toward more bleeding complications
with transbronchial cryobiopsies. The increased risk of bleeding is due to the larger
biopsies thus obtained, and the necessity to retrieve bronchoscope and cryoprobe en-bloc as
biopsies are too large to be pulled through he working channel of the bronchoscope,
preventing the proceduralist from keeping he bronchoscope wedged in the biopsied segment
allowing bleeding tamponade. Accordingly, most proceduralists perform cryobiopsy with
prophylactic placement of bronchial blocker positioned proximal to the selected lobe to
occlude the segmental airway after biopsy. While this technique has essentially eliminated
the risk of life-threatening bleeding after cryobiopsies, significant bleeding complications
persist and can occasionally substantially lengthen the duration of the procedure, leading to
premature termination and potentially quantitatively inadequate biopsy acquisition.

Conceptually it seems that the ability to select a less vascular area for a somewhat larger
cryobiopsy may result in decreased risk of hemorrhage and/or reduction in bleeding severity.
Average peripheral cryobiopsy size varies significantly and may be dependent on freezing time
and cryoprobe size. Increase in resource utilization due to the use of radial ultrasound
could be offset by a decrease in complication rate, decreased procedural time and potentially
decreased endobronchial blocker need. This use of radial probe ultrasound use has not been
widely reported in literature except for a recent single center retrospective review of 10
patients undergoing transbronchial cryobiopsies for ILD(Berim, 2017). Six of these patients
underwent vascular localization with radial probe endobronchial localization with trends
towards less bleeding.

The purported benefit of radial ultrasound-guided transbronchial cryobiopsy is the avoidance
of excessive bleeding, which has been associated with this procedure. With the systematic use
of a prophylactic bronchial blocker, an ideal endpoint for this pilot study would be the time
spent obtaining each biopsy. We propose to study in a prospective, double-blind, randomized
controlled fashion, the efficacy of radial endobronchial ultrasound (in combination with
fluoroscopy) guided transbronchial cryobiopsy as compared to conventional fluoroscopy guided
cryobiopsy in reducing time needed to achieve hemostasis (primary endpoint) and need for
additional modalities to control bleeding and size of biopsies obtained (secondary
endpoints).

Inclusion Criteria:

1. Referral to interventional pulmonary services for diagnostic transbronchial cryobiopsy
for diffuse parenchymal lung disease.

2. Transbronchial cryobiopsy is determined to be appropriately indicated as determined by
consulting interventional pulmonologist.

3. Age > 18 years

Exclusion Criteria:

1. Inability to provide informed consent

2. Study subject has any condition that interferes with safe completion of the study
including:

1. Coagulopathy, with criteria left at the discretion of the operator

2. Respiratory insufficiency with DLCO < 30% or baseline requirements of oxygen >2
liters

3. Hemodynamic instability with systolic blood pressure <90 mmHg or heart rate > 120
beats/min, unless deemed to be stable with these values by the attending
physicians

3. Patients representing vulnerable populations (prisoners, pregnant women, etc.)