AJTCCM VOL. 29 NO. 3 2023 101
EDITORIAL
Transbronchial lung biopsy (TBLB) using biopsy forceps was initially
introduced in the mid-1960s for sampling peripheral lung lesions
or tissue.[1] However, despite the perfection of this technique over
several decades, it still has the disadvantages of retrieval of small-
sized, mainly centrilobular lung tissue samples and the inadvertent
introduction of artifacts in the biopsied tissue (mainly bleeding and
crush artifacts). ese factors complicate laboratory processing and
histopathological analysis in the diagnosis of diuse parenchymal
lung disease (DPLD).[2,3] Even when combined with clinical
examination and high-resolution computed tomography (HRCT),
TBLB therefore only achieved a diagnosis in ~30% of patients with
suspected DPLD.[4,5] Despite these drawbacks, TBLB has oen been
attempted prior to surgical lung biopsy (SLB), which is regarded
as the ‘gold standard’, owing to patient preference and to avoid
more costly surgery and its attendant complications, including high
morbidity (bleeding, prolonged air leak, persistent thoracic pain,
cardiac arrhythmias, infectious complications).[6,7] An alternative
was to sample the lung using percutaneous image-guided biopsy.
However, this method is also associated with suboptimal yield in
DPLD (~45%),[8] and pneumothorax rates are high (20 - 45%).
[9] TBLB and image-guided biopsy are therefore techniques with a
poor diagnostic yield, signicant complication rates, especially with
image-guided percutaneous needle biopsy, and a high associated rate
of onward referral for SLB.
e poor performance of TBLB and other approaches has now
been superseded by a new technique, peripheral transbronchial lung
cryobiopsy (TBLC). Historically, the rst bronchoscopic cryobiopsy
procedure was described in 1978,[10] where it was used for debulking
tumours occluding the lumen of larger airways.[11] More recently,
we have seen a reintroduction of cryoprocedures for diagnostic
purposes.[12] e technology leverages the Joule-omson eect,
which describesthe rapid expansion of compressed gas when forced
through a valve. is rapid expansion leads to a drastic drop in the
temperature of the gas, resulting in the adherence of moist lung
tissue to the tip of the probe, which is then pulled back to retrieve
a lung biopsy sample. e ERBECRYO 2 equipment currently used
to perform the cryobiopsies uses pressurised carbon dioxide at 45
bar to cool the probe tip to ~–80o. e diameter of the cryoprobe
(1.1 mm, 1.7 mm, 1.9 mm or 2.4 mm) and the freezing time are the
two key determinants of the size of the biopsy specimens obtained.
Most guidelines recommend that the procedure be performed under
anaesthesia via a secured airway (usually an armoured endotracheal
tube or rigid bronchoscopy). e two main complications of this
procedure are bleeding (mitigated with bronchial balloon blockers)
and pneumothorax. However, in busy pulmonology units and
respiratory divisions, and oen in the hospital setting of overworked
anaesthetic departments, the need for anaesthesia and endotracheal
intubation represents a huge barrier to undertaking the procedure,
not to mention increasing costs substantially. So, can this procedure
be undertaken safely using conscious sedation (as is performed
withTBLB)?
In this issue of AJTCCM, Mohanrao etal.[13] address this critical
question. ey performed TBLC on 87 patients with suspected DPLD in
tandem with forceps biopsy from the same segments, under conscious
sedation. e TBLC procedure in this study was performed using a
1.9 mm Erbe cryoprobe with a 4 - 5-second freezing time. An Arndt
bronchial blocker was used along with topical therapy (adrenaline) to
control bleeding. ey showed that TBLC had a signicantly superior
diagnostic yield compared with TBLB (n=69/87 (79.3%) v. n=27/87
(31.0%)) when combined with multidisciplinary discussion. However,
oxygen desaturation was observed in 30/87 patients (34.5%) during the
TBLC procedure, while none of the patients experienced desaturation
during TBLB. Pneumothorax developed in 12 of the patients (13.8%),
of whom 11 required high-ow oxygen therapy and 1 insertion of
an intercostal drain with a 3-day hospital stay. Moderate bleeding
mandating the use of a bronchial blocker and/or topical treatment
occurred in most of the patients (~72%), with no reported incident
of major bleeding.
e authors must be commended on performing this interesting but
dicult study. What are the implications of the ndings? Although most
guidelines recommend performing TBLC via a secured airway using an
endotracheal tube or rigid bronchoscopy, the authors have shown that
it can be done under conscious sedation in a specic context. However,
the bleeding rate was much higher than in other studies, ~75% v. ~25%.
e possible reasons include undiagnosed pulmonary hypertension,
as the patients were not screened for this; coughing, as patients were
not deeply sedated; and the most common diagnosis in this series
being hypersensitivity pneumonitis, in contrast to other studies,
which may have contributed to the increased incidence of bleeding.
e pneumothorax rate was also higher than what has traditionally
been reported with TBLB, but this could simply represent an additive
eect: the study design did not allow for the accurate quantication
of adverse events, especially pneumothorax, as it would be dicult to
ascertain exactly when the event occurred, i.e. during TBLB or TBCB.
e major advance of this study is conrmation that conscious sedation
may be compatible with low severe bleeding rates, as the main reason
for using endotracheal intubation is to maintain a safe airway in the
event of major bleeding. Signicantly, more recent data on cryobiopsy
using a 1.1 mm sheathed cryoprobe support use with a laryngeal mask
airway without bronchial blockers,[14] adding to the condence in this
approach. Another advantage of the study by Mohanrao etal.[13] was the
resource-poor setting; TBLC was useful in patients with DPLD, but also,
surprisingly, in those with tuberculosis (although it is not clear whether
the diagnosis was made using Xpert or was purely histological).
Another conundrum facing those of us in the eld is the order in
which bronchoscopic investigations should be performed, i.e. when
one has access to endobronchial ultrasound-guided transbronchial
ne-needle aspiration (EBUS-TBNA), TBLB and TBLC. Our approach
is to perform EBUS rst in all patients with suspected DPLD who have
signicantly enlarged mediastinal lymph nodes. All patients with a
non-diagnostic mediastinal lymph node biopsy on rapid on-site
evaluation should proceed to TBLB during the same procedure. Given
the additional logistical challenges, costs and risks associated with
TBLC, this procedure is reserved for patients with a non-diagnostic
EBUS/TBLB and for patients with DPLD with a high likelihood of
a non-bronchocentric disease process such as pathologies associated
e cool new kid on the block: Lung cryobiopsy
102 AJTCCM VOL. 29 NO. 3 2023
EDITORIAL
with non-definite usual interstitial pneumonia, and nonspecific
interstitial pneumonia patterns on HRCT – the bottom line is that
this decision will be centre specific and dependent on capacity.
Furthermore, choosing between TBLB and TBCB may depend on
several other factors, including patient preference and available
resources. TBLC will also be useful for the ~15% of patients who
remain unclassiable in large series who are too sick for SLB. However,
there are still several unanswered questions. One is, could a similar
diagnostic yield be achieved with the smaller 1.1 mm sheathed probe
(with a slightly higher freezing time of ~7 seconds), while keeping
bleeding and pneumothorax rates similar to forceps-linked TBLB?
Second, which area on HRCT should be biopsied, and should more
than one region be biopsied? ese issues will need to be resolved in
future studies.
It should be noted that TBLC is not a panacea, and ~20% of patients
in Mohanrao et al.’s [13] series still had an inconclusive diagnosis.
While TBLC has a better yield than TBLB, it is not perfect and is
still a technique complementary to SLB. Patients should therefore
be selected by multidisciplinary teams, and the procedure should
be performed in close co-operation with cardiothoracic surgeons.
Indeed, interventional pulmonology remains a hot topic, and TBLC
is certainly the new ‘coolest kid on the block’!
A Esmail, MD, FCP (SA)
Centre for Lung Infection and Immunity, Division of Pulmonology,
Department of Medicine and UCT Lung Institute, University of Cape Town;
South African MRC/UCT Centre for the Study of Antimicrobial Resistance,
University of Cape Town, South Africa
ali.esmail@uct.ac.za
K Dheda, MB BCh (Wits), FCP(SA), FCCP, PhD (Lond), FRCP (Lond)
Head: Division of Pulmonology, Department of Medicine, University of Cape Town,
South Africa; Professor of Mycobacteriology and Global Health, London School
of Hygiene and Tropical Medicine, United Kingdom; Director: Centre for Lung
Infection and Immunity, University of Cape Town Lung Institute, South Africa
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Afr J Thoracic Crit Care Med 2023;29(3):e1494.
https://doi.org/10.7196/AJTCCM.2023.v29i3.1494
