The Comparative Study of Electromagnetic Navigation Bronchoscopic With Ultra-thin Cryobiopsy and Forceps Biopsy in the Diagnosis of Peripheral Pulmonary Nodules
Phase: NA
Conditions: Diagnosis
Sponsor: Beijing Chao Yang Hospital

The comparative study of Electromagnetic Navigation Bronchoscopic with Ultra-thin Cryobiopsy and Forceps Biopsy in the
Diagnosis of Peripheral Pulmonary Nodules.
Version: 1.2
Version date: 2025-07-07
1
RESEARCH PROTOCOL
Project
Name
(English):
The
comparative
study
of
Electromagnetic Navigation Bronchoscopic with Ultrathin
Cryobiopsy
and
Forceps
Biopsy
in
the
Diagnosis
of
Peripheral Pulmonary Nodules
Lead research unit: Beijing Chaoyang Hospital affiliated to Capital
Medical University
Department: Department of Respiratory and Critical Care Medicine
Version number: 1.2
Version date: 2025.07.07

The comparative study of Electromagnetic Navigation Bronchoscopic with Ultra-thin Cryobiopsy and Forceps Biopsy in the
Diagnosis of Peripheral Pulmonary Nodules.
Version: 1.2
Version date: 2025-07-07
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I. REAEARCH BACKGROUND
The Global Cancer Statistics Report shows that lung cancer is currently the second
most prevalent cancer globally. According to data released by the National Cancer
Center in 2022, China recorded 4.064 million new cases and 2.414 million deaths
from malignant tumors in 2016, while lung cancer accounted for 828,000 new cases
and 658,000 deaths [1]. The overall cancer incidence in China continues to rise, with
lung cancer remaining the leading cause of both incidence and mortality. Lung
cancer remains the primary cause of new cases and deaths in China, which may be
attributed to the high smoking rate. The "2020 China Smoking Hazards Report"
issued by the National Health Commission indicates that between 2007 and 2017,
the global smoking rate among people aged 15 and above decreased to 19.2%. In
contrast, Chinas smoking rate among people aged 15 and above reached 26.6% in
2018, with 68.1% of non-smokers exposed to secondhand smoke in public places.
With the rapid advancement and widespread adoption of imaging technologies, chest
CT has become standard equipment in secondary and even primary healthcare
institutions. This has enabled earlier detection of pulmonary nodules, where malignant
and benign nodules may exhibit similar imaging characteristics in early stages.
Accurate and timely diagnosis is therefore crucial for determining treatment strategies
and prognosis, which holds significant importance for clinical management of
pulmonary nodules. However, relying solely on clinical and imaging data often fails
to achieve definitive diagnoses. In such cases, invasive lung nodule biopsy is
recommended to provide sufficient specimens for pathological evaluation and
subsequent molecular analysis.
With advancements in respiratory interventional techniques, the overall diagnostic
rate of pulmonary nodules guided by bronchoscopy can exceed 70%, while
electromagnetic navigation bronchoscopy provides enhanced access to the entire lung
[2-5]. Electromagnetic navigation bronchoscopy (ENB) utilizes three-dimensional
reconstruction of CT images to create virtual bronchial images. The electromagnetic

The comparative study of Electromagnetic Navigation Bronchoscopic with Ultra-thin Cryobiopsy and Forceps Biopsy in the
Diagnosis of Peripheral Pulmonary Nodules.
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positioning sensor at the bronchoscope tip provides three-dimensional spatial
coordinates and directional information, allowing real-time visualization of lesion
locations on pre-generated navigation maps. By comparing intra-lens images with
reconstructed three-dimensional bronchial trees and lesion positions, ENB accurately
guides bronchoscopy to target lesions. Current primary biopsy methods for peripheral
lung nodules include forceps biopsy (TBFB), needle aspiration biopsy (TBNA), and
cryobiopsy (TBCB). Among these, forceps biopsy remains the predominant
ENB-guided approach. Meta analyses indicate a positive detection rate of 69.4-75.6%
for ENB-guided biopsies [4], though this remains slightly lower than diagnostic
accuracy in surgical specimens. Additionally, the growing demand for molecular
diagnostics has driven increased need for larger sample sizes. A new method for
sampling peripheral lung nodules, Electromagnetic Navigation Bronchoscopic Guided
Cryobiopsy (ENB-TBCB) is poised for clinical implementation, combining the
advantages of cryobiopsy and ENB technology. Compared to conventional TBFB,
this innovative method enables larger tissue sampling while demonstrating lower
complication rates (bleeding and pneumothorax) and enhanced safety with 1.1mm
cryobiopsy probes, compared to standard 2.4mm and 1.9mm probes [6-9]. Studies
have shown that 1.1mm probes provide sufficient tissue samples for lung cancer
biopsy, meeting requirements for DNA/RNA sequencing [10]. These factors confirm
the technical feasibility of ENB-TBCB, which can be safely performed by physicians
proficient in ENB techniques. However, before its routine clinical adoption, extensive
controlled trials are needed to evaluate diagnostic accuracy and safety compared to
traditional TBFB, as well as to determine whether TBFB combined with ultra-thin
cryosurgical probes can outperform conventional bronchoscopic biopsy. This would
provide crucial guidance for optimizing diagnostic strategies in peripheral pulmonary
nodule management.
Therefore, this project aims to validate the feasibility, effectiveness, and safety of
electromagnetic navigation bronchoscopy-guided cryobiopsy in diagnosing peripheral
lung nodules through a national multicenter randomized controlled trial. By
establishing traditional TBFB as the control group and ultrathin cryoprobe biopsy as

The comparative study of Electromagnetic Navigation Bronchoscopic with Ultra-thin Cryobiopsy and Forceps Biopsy in the
Diagnosis of Peripheral Pulmonary Nodules.
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the experimental group, the study seeks to provide an efficient and minimally invasive
diagnostic method for peripheral pulmonary nodule detection.
II. RESEARCH OBJECTIVES
A national multicenter randomized controlled study was conducted to verify the
safety and effectiveness of electromagnetic navigation bronchoscopy ultrathin
cryobiopsy compared with biopsy forceps biopsy in the diagnosis of peripheral lung
nodules.
III. RESEARCH PROGRAMME AND TECHNICAL ROUTINE
3.1 Research design
This study employed a prospective, multicenter, randomized controlled trial design
to continuously enroll patients with idiopathic peripheral lung nodules, suspected
malignant pulmonary nodules, or indeterminate nodule characteristics. Participants
were randomly assigned (1:1) into two groups: the experimental group received
ultrathin cryoprobe biopsy and the control group underwent biopsy forceps biopsy.
The study compared pathological confirmation rates, incidence of procedure-related
complications, and specimen size quality metrics.
3.2 Research subjects
3.2.1 Study population
The study population was hospitalized patients who received treatment in Beijing
Chaoyang Hospital (central unit) and participated in the research unit from August
2025 to July 2027, and had chest CT nodules in the peripheral lung, suspected
malignant pulmonary nodules or unknown nature of nodules, and planned to perform
electromagnetic navigation bronchoscopy lesion biopsy.
3.2.2 Inclusion criteria
Participants in this study must meet all of the following criteria:

The comparative study of Electromagnetic Navigation Bronchoscopic with Ultra-thin Cryobiopsy and Forceps Biopsy in the
Diagnosis of Peripheral Pulmonary Nodules.
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①Age 18 or above, male or female;
②Chest CT found lung nodule, suspected malignant nodule or unknown nature
needs biopsy to confirm;
③Chest CT indicates that the nodule to be biopsied is located in the bronchus below
the segment, with the maximum diameter of the nodule ≥8mm and ≤30mm, which
is not accessible in the conventional bronchoscopy view;
④If chest CT shows multiple nodules in the lung, one of the lung nodules is
selected as the target lesion;
⑤Voluntarily accept electromagnetic navigation bronchoscopy and meet the
preoperative requirements of bronchoscopy;
⑥Good compliance, able to cooperate with the study observation, fully informed
about the purpose and method of the study, accept the potential risks of the two
biopsy methods, agree to participate in the study, and sign the informed consent
form.
3.2.3 Exclusion criteria
Eligibility for exclusion from this study will be determined by meeting any of the
following criteria:
①Contraindications for bronchoscopy include: active massive hemoptysis; recent
myocardial infarction or unstable angina attack; severe cardiopulmonary dysfunction;
severe hypertension and arrhythmia; uncorrectable bleeding tendency or severe
coagulation disorders (e.g., platelet count <60×10^9/L), uremia; severe pulmonary
hypertension;
severe
superior
vena
cava
obstruction
syndrome;
intracranial
hypertension; acute cerebrovascular events; aortic dissection or aneurysm; multiple
pulmonary bullae; extreme systemic failure; breastfeeding or pregnant women, or
female patients undergoing pregnancy planning.
②The site of planned biopsy has high risk of bleeding such as bronchial artery
penetration or suspected lung metastasis of renal cancer;

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③The body contains electromagnetic source implantation equipment;
④There are contraindications for anesthesia; allergic to anesthetics; or have a
history of severe allergies, hereditary allergies;
⑤Those who participated in other studies within 3 months and did not quit or end
will affect the observation of this study;
⑥Unwilling to participate in this study and unwilling to accept the follow-up plan;
⑦Other circumstances that the researcher considers unsuitable for participation in
this study.
3.2.3 Midterm withdrawal criteria
Patients who meet the inclusion criteria but do not complete the study for some
reason, including subjects who withdraw of their own accord and those who decide
to withdraw.
①Subjects are entitled to withdraw from the trial at any time without reason and to
be given appropriate follow-up or recommended as appropriate treatment.
②Withdrawal from the trial at the investigators discretion: if any of the following
occurs, after clinical relevance has been assessed,
If the investigator determines that the subject is unable to continue the clinical trial,
the subject may withdraw from the trial in advance:
A medical condition occurs and the investigator determines that continued
participation may endanger the safety of the subject;
Other managerial reasons.
3.3 Research steps and research endpoints
3.3.1 Intervention steps
①Collect patients with peripheral lung nodules that meet the discharge criteria
continuously, and enroll them in the study after signing the informed consent.

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②Collect preoperative chest CT and other laboratory test data of patients.
③According to the pre-prepared random envelope, subjects were randomly
assigned to the ultrathin cryoprobe biopsy group and biopsy forceps biopsy group
(1:1).
④Thin-layer CT (1mm) was used for 3D reconstruction before surgery to plan the
path of bronchoscopy with electromagnetic navigation.
⑤Improve routine preoperative preparation, and combine intravenous anesthesia
with high-frequency mechanical ventilation or tracheal intubation mechanical
ventilation during surgery.
a) Ultrathin
Cryoprobe
Biopsy
Group
(TBCB):
After
completing
routine
bronchoscopy, the probe is navigated to the nodule site using electromagnetic
guidance. The biopsy site is confirmed through radial ultrasound and/or cone-beam
CT imaging. A 1.1mm cryoprobe is inserted via the electromagnetic navigation
catheter, with each freeze lasting 4-10 seconds. This procedure is repeated 2-3 times
to obtain at least two tissue samples, each measuring no less than 5mm in diameter.
b) Forceps Biopsy Group (TBFB): After completing routine bronchoscopy, the team
navigates to the nodule site using electromagnetic navigation guidance. The biopsy
site is confirmed through radial ultrasound and/or cone-beam CT imaging. A 1.8mm
biopsy forceps is inserted via the electromagnetic navigation catheter to obtain at
least five tissue samples through precise clamping.
c) During the procedure, radial ultrasound and/or cone-beam CT can be used for
localization verification. The biopsy specimens obtained from both groups are fixed
in formalin and sent for pathological examination. The pathological diagnosis is
confirmed when two pathologists independently evaluate the results. If their
assessments differ, a third experts evaluation is conducted, with final determination
made through consultation among all three specialists.
⑥Data Collection: Clinical data should include medical history, physical signs,

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laboratory
tests,
pulmonary
function
evaluations,
and
imaging
studies.
Documentation should cover procedure duration, specimen quantity, surgical
complications such as hemorrhage, pneumothorax, or infections (including those
occurring within 7 postoperative days), severity assessment of complications like
bleeding or pneumothorax, and pathological findings.
⑦Follow-up: Short-term follow-up involves collecting data at 4 weeks post-surgery
to evaluate the occurrence of delayed complications such as bleeding, pneumothorax,
or infections. Long-term follow-up extends to 12 months post-operation for patients
with unclear histopathological diagnoses, assessing their final diagnosis through
imaging monitoring of pulmonary nodule absorption or stability, along with other
invasive diagnostic evaluations.
3.3.2 Study endpoints
1）Subject outcome measures:
Indicator 1, clear histopathological diagnosis, such as malignant lesions, benign
lesions with clear pathogen (granuloma, tuberculosis, etc.).
Indicator 2, Clinical follow-up for 12 months to obtain a clear diagnosis. Diagnostic
examinations or treatment plans related to pulmonary lesions should be collected
during the follow-up period, such as biopsy or invasive surgery, imaging, and
microbial evaluation.
Indicator 3, such as histological diagnosis of nonspecific benign lesions or
non-diagnostic pathology, with imaging follow-up for 12 months, the lesion is
absorbed or unchanged.
2）Main destinations:
①The pathological diagnosis rates of ultrathin cryoprobe biopsy and forceps biopsy
were calculated separately.

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Pathological specimens carry diagnostic significance. When demonstrating definitive
malignant outcomes or specific benign findings, they can elucidate pathological
characteristics and guide subsequent treatment. Non-specific benign lesions
(acute/chronic inflammation) and non-diagnostic abnormalities (atypical cells, normal
lung parenchyma, interstitial changes, insufficient effective tissue) are generally
considered non-pathologically significant. For patients with non-specific benign or
non-diagnostic pathology identified in this study, definitive diagnosis is confirmed
through 12-month clinical/imaging follow-up (or until additional surgery or
confirmation of regression without cancer treatment). This approach ensures accurate
identification of true negative or false-negative outcomes.
Pathological diagnosis rate: (number of pathological malignant diagnosis cases +
number of pathological specific benign diagnosis cases)/total number of cases
②The sensitivity, specificity, positive predictive value and negative predictive value
of the two groups of different biopsy methods for diagnosing benign and malignant
pulmonary peripheral nodules were calculated based on the final diagnostic results.
Sensitivity: Number of cases diagnosed as malignant/number of all cases diagnosed as
malignant after 12 months of follow-up
Specificity: Number of benign cases diagnosed/number of all benign cases followed
up to 12 months
Positive predictive value: number of true malignancies/number of malignant cases
diagnosed by biopsy
Negative predictive value: number of true benign cases/number of benign cases
diagnosed by biopsy
2) Secondary endpoints:
Navigation success rate: the biopsy tool successfully reached the target lesion, which

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was confirmed and identified by navigation software and imaging.
Biopsy operation time: from the start of application of two biopsy tools to the final
removal of biopsy tools.
Time per biopsy: time of operation/number of attempts to biopsy.
Successful acquisition of core tissue: Acquisition of samples for pathological
examination.
Size and quality of tissue samples: measure the size (length * width) of each tissue
with a ruler, number, and pathological experts assess whether the sample size is
adequate (including effective histiocytes and molecular diagnosis).
Related complications: pneumothorax, hemorrhage, respiratory failure, infection,
and severe complications requiring tracheal intubation and mechanical ventilation
transfer to intensive care unit.
3.4 Adverse events/comorbidities observation
3.4.1 Recording and reporting of adverse events
During treatment, clinical adverse events may occur in participants. When such
events (including major adverse events) are identified, they must be documented in
detail on the Case Report Form (CRF), including the time of occurrence, clinical
manifestations, management procedures, duration, progression, and relationship to
the intervention. Patients with abnormal laboratory test results should be followed up
until their test results return to normal levels, reach baseline intervention values, or
are confirmed unrelated to the intervention. In cases of severe adverse events, a
Serious Adverse Event Form (SAE Form) must be completed and reported to the
sponsor, ethics committee, CFDA, regulatory authorities, and health administration
departments within 24 hours.
3.4.2 Severity assessment of adverse events/comorbidities
Level 1: Mild; asymptomatic or mild; only clinically or diagnostically observed; no

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treatment required.
Level 2: Moderate; requires small, local or non-invasive treatment; limited
instrumental daily living activities for their age.
Level 3: severe or medically significant but not immediately life-threatening;
resulting in hospitalization or prolonged hospital stay; disability; and impaired
self-perceived daily living activities.
Level 4: Life-threatening: requires urgent treatment.
Level 5: Death associated with adverse events.
Instrumental daily activities refer to cooking, buying clothes, using the telephone,
managing money and so on.
Self-sustaining daily activities refer to bathing, dressing and undressing, eating,
washing, taking medicine, etc., without being bedridden.
3.4.3 Occurrence and management of adverse events/comorbidities
Potential intraoperative and postoperative complications of pulmonary cryobiopsy
and bronchoscopy include hemorrhage, pneumothorax, coughing, air embolism,
pleural effusion, and pulmonary inflammation. Bronchoscopy procedures may
involve risks such as anesthesia-related drug allergies, bleeding, infections,
temporomandibular
joint
dislocation,
radiation
exposure
during
fluoroscopy,
pneumothorax, cardiovascular accidents, laryngospasm, laryngeal edema asphyxia,
respiratory arrest, cardiac arrest, and even death. The study-related examination of
cryobiopsy may increase associated risks including hemorrhage, pneumothorax, and
fluoroscopy-related
radiation
exposure.
For
potential
intraoperative
and
postoperative complications, close monitoring and follow-up will be conducted
regardless of their relevance to the study. Appropriate interventions will be promptly
implemented
based
on
investigator
evaluations
and
clinical
guidelines.
Recommended management strategies for major potential complications are as
follows:

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①Pneumothorax: Intraoperative or delayed pneumothorax may occur. Small
pneumothorax may not be treated, and medium to large pneumothorax can be
thoracentesis or closed drainage device placed in the chest cavity. If tension
pneumothorax occurs, biopsy should be stopped immediately.
②Hemorrhage: Minor intraoperative bleeding can be managed with suction therapy.
Moderate bleeding may require hemostatic agents or balloon occlusion. Immediate
cessation of biopsy procedures is necessary for massive hemorrhage, with patients
being transferred to the intensive care unit for further treatment. Interventional
embolization or thoracotomy may be performed when required. Postoperative
hemoptysis typically follows a self-limiting course.
③Lung infection: chest X-ray or chest CT scan (recommended) for confirmation,
and adjust antibiotics according to sputum, blood or pus culture results; if chest
X-ray or chest CT scan indicates lung/cavity abscess, catheter drainage should be
placed.
④Pleural effusion: Generally, observation or conservative treatment can be done. If
moderate to large pleural effusion occurs, puncture aspiration or closed thoracic
drainage should be performed.
⑤Others: appropriate treatment measures should be taken in time according to the
researchers evaluation and clinical routine diagnosis and treatment norms.
3.5 Sample size calculation
To compare differences between the groups, based on meta-analyses [4] of
electromagnetic navigation bronchoscopy (Prasanth Balasubramanian, 2024) and a
preliminary exploratory study [11] of ultrathin cryoprobe biopsy for peripheral lung
nodules (Soo Han Kim, 2023), we set the diagnostic rates for ENB cryobiopsy and
forceps biopsy at 90% and 72.7% respectively. Using a 90% confidence level,
α=0.05, and a 10% dropout rate, we performed sample size calculations using PASS
21.0 software. The results indicated that each group required 114 participants,
totaling 228 subjects. We ultimately planned to enroll 228 participants.

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3.6 Data collection and analysis
3.6.1 Data collection
①Baseline data: demographic information, medical history, symptoms and signs,
physical examination, hematological examination, imaging characteristics, etc.;
②Operation related information: operation time, sample number, etc.;
③Pathological data: pathological results, tissue sample quality, molecular detection
results, etc.;
④Safety evaluation data: type of complications, treatment methods, length of
hospitalization, etc.;
⑤Postoperative follow-up: For those who failed to obtain clear evidence of
malignancy in the pathology, the nature of the nodule was determined by imaging or
whether a repeat biopsy was performed after 12 months of follow-up.

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Research process table
Preoperative
During
surgery
Postoperative
Follow.up
Visitation
1
2f
3f
4
5
6
7
Number of days enrolled
D-30~D-1
D0
D1-7
Postoperative
1 month
Postoperative
3 months
Postoperative
6 months
Postoperative
1 2 months
Visit window (number of
days)
/
/
/
±7
±15
±15
±15
Sign the informed consent
form
×
Inclusion and exclusion
criteria
×
Demographic information
collection
×
history-taking
×
Collection of combined
medication
×
×
×
×
vital sign
×
×
×
×
chest CT
×
×
×
×
pulmonary function test
×
laboratory examination
×
Electromagnetic navigation
bronchoscopy
×
Radial ultrasound /CBCT
×

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biopsy
×
Chest X-ray
×
pathological examination
×
Clinical diagnostic results
×
Collection of adverse events
×
×
×
Note: Patients with histopathological examination of malignancy do not require follow-up.

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3.6.2 Statistical analysis
Statistical analysis was performed using SPSS 22.0 software (IBM, Armonk, NY,
USA). Demographic and radiological data were presented with mean ± standard
deviation for continuous variables and frequency/percentage for categorical variables.
Intergroup comparisons of continuous variables employed t-tests, while categorical
variables were analyzed using chi-square tests (or Fishers exact test). The McNemar
test was used to evaluate differences in diagnostic rates between two methods. A
p-value <0.05 was considered statistically significant.
3.7 Quality control measures
①Strictly implement the bronchoscopy operation procedures, and the intraoperative
operation is completed by the same operator. The operator has more than 50
experience in electromagnetic navigation bronchoscopy examination to avoid
operational differences.
②The pulling force of intraoperative cryobiopsy and the clamping force should be
standardized, and the pulling speed of cryobiopsy and the closing speed of clamping
should be consistent.
③The pathological diagnosis results are identified by two pathologists back to back,
and the results are consistent, that is, the diagnosis is confirmed; if the results are
inconsistent, a third pathologist is identified, and finally determined by the three
experts after consultation.
④Intraoperative image localization verification. Radial ultrasound and/or cone beam
CT were used to confirm the biopsy position before the two biopsy methods.
⑤Participants in the study must undergo unified training, with unified recording
methods and judgment criteria. Researchers should truthfully, detailedly and carefully
record all contents of the case report form according to the requirements of the case
report form, so as to ensure that the content of the subjects case report form is
complete, true and reliable.

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IV. STUDY RELEVANT ETHICS
4.1 Ethics Committee review
This study was conducted in compliance with the "Regulations on the Supervision
and Administration of Medical Devices (2014)", "Good Clinical Practice for Medical
Devices (2016)", "Helsinki Declaration", and other relevant laws, regulations, and
trial protocols. Prior to the commencement of the trial, the principal investigator must
submit the trial protocol, informed consent forms, and all related documents to the
ethics committee for approval before proceeding with clinical trials. The sponsor is
required to promptly report any serious adverse events occurring during the study,
including participant risks and other issues. Any modifications to the trial protocol
must first obtain prior approval from the ethics committee and be formally filed with
them.
4.2 Informed consent
All participants must complete both oral and written disclosures of the clinical trial
details and sign an informed consent form before being enrolled in the study. The
signed consent forms are made in duplicate: one copy is retained by the investigator
in the designated clinical trial management records, while the other is kept by the
participant.
V. CRRPTOSECURITY
The findings from this research project may be published in medical journals.
However, we will maintain patient information confidentiality as required by law.
Patient personal data will not be disclosed unless legally mandated. When necessary,
government regulatory authorities and hospital ethics committees may access patient
records in accordance with established protocols.
VI. DATE MANAGEMENT AND SECURITY
6.1 Data input and verification

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The patient screening number combines the S+ center code (a two-digit Arabic
numeral, e.g., 01) with a three-digit Arabic numeral, such as S01001. The enrollment
number uses a three-digit Arabic numeral, for example: 001. Each research center
collects the patients CRF form and inputs it into the Electronic Data Capture (EDC)
system. A computerized verification system is then used to double-check the entered
data, ensuring its completeness and accuracy.
6.2 Data management
The main researchers will manage the data and save them in paper and electronic
form. Except for the members of the research group, the data will not be exposed to
anyone outside the research group.
VII. EXPECTED SCHEDULE AND COMPLETION DATE OF THE
RESEARCH PROJECT
Expected progress: to clarify the diagnostic efficacy and safety of ultrafine frozen
probes for peripheral lung nodules under navigated bronchoscopy.
Completion date: July 2028
August 2025-July 2027: Conduct case screening and study intervention.
August 2027 to July 2028: Conduct data processing, statistical analysis and summary
of all technical data, write a paper, and submit the final report.
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Zheng, R., et al.,
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2(1): p. 1-9.
2.
Zhang, W., et al., Meta-analysis of the diagnostic yield and safety of electromagnetic
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3.
Mehta, A.C., et al., The Evolutional History of Electromagnetic Navigation Bronchoscopy:
State of the Art. Chest, 2018. 154(4): p. 935-947.
4.
Balasubramanian, P., et al., Diagnostic yield and safety of diagnostic techniques for
pulmonary lesions: systematic review, meta-analysis and network meta-analysis. Eur Respir
Rev, 2024. 33 (173).
5.
Tang, Y., et al.,
Transbronchial lung cryobiopsy for peripheral pulmonary lesions. A

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narrative review. Pulmonology, 2024. 30(5): p. 475-484.
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Bondue, B., et al., Trans-bronchial lung cryobiopsy in patients at high-risk of complications.
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Matsumoto, Y., et al.,
Diagnostic Outcomes and Safety of Cryobiopsy Added to
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Nakai, T., et al., Safety profile and risk factors for bleeding in transbronchial cryobiopsy using
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Nakai, T., et al., Diagnostic Utility and Safety of Non-Intubated Cryobiopsy Technique Using
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Kim, M.H., et al., Next-generation sequencing using tissue specimen collected with a 1.1
mm-diameter cryoprobe in patients with lung cancer. Respirology, 2024. 29(4): p. 333-339.
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Kim, S.H., et al., Clinical outcomes of transbronchial cryobiopsy using a 1.1-mm diameter
cryoprobe for peripheral lung lesions - A prospective pilot study. Respir Med, 2023. 217: p.
107338.