Lung Navigation Ventilation Protocol to Optimize Biopsy of Peripheral Lung Lesions : Journal of Bronchology & Interventional Pulmonology

Journal Logo

Original Investigations

Lung Navigation Ventilation Protocol to Optimize Biopsy of Peripheral Lung Lesions

Bhadra, Krish MD*; Setser, Randolph M. PhD; Condra, William RT(R)*; Pritchett, Michael A. DO, MPH

Author Information
Journal of Bronchology & Interventional Pulmonology 29(1):p 7-17, January 2022. | DOI: 10.1097/LBR.0000000000000756
  • Free

Abstract

BACKGROUND

Despite the continual evolution of navigational bronchoscopy platforms, including endoluminal robotics, fluoroscopic-based electromagnetic navigation and shape sensing platforms, bronchoscopy for the biopsy of small peripheral lung lesions (PLLs) remains challenging. The largest study to date of electromagnetic navigational bronchoscopy (ENB), NAVIGATE, reported a 12-month diagnostic yield of 73% for experienced users.1 All forms of guided bronchoscopy in 2 meta-analyses reported a diagnostic yield of 70% to 73%.2,3

Guided bronchoscopy techniques are increasingly utilizing intraprocedural 3-dimensional (3D) images to visualize the location of catheters and biopsy tools relative to target PLLs. For instance, cone beam computed tomography (CBCT) used in conjunction with ENB has shown promising results even for small lesions, with 93.5% diagnostic accuracy utilizing criteria from the NAVIGATE trial and diagnostic yield of 84% based on the definition used in the AQuIRE registry.4,5 In addition, new devices using digital tomosynthesis have been recently described. A single center trial demonstrated digital tomosynthesis combined with ENB increased diagnostic yield from 54% to 79%.6

Intraprocedural 3D images are typically acquired during suspended respiration. Despite this, degradation of 3D image quality can occur due to respiratory motion, atelectasis or device artifacts, all of which must be minimized. The I-LOCATE trial demonstrated 89% of patients undergoing navigational bronchoscopy had atelectasis based on peripheral radial probe ultrasound survey.7 While intense effort from device manufacturers have attempted to better locate PLLs and reduce computed tomography (CT)-to-body divergence, dedicated ventilation strategies for 3D image-guided navigational bronchoscopy have yet to be optimized, or even well studied.8–12 Here we describe a lung navigation ventilation protocol (LNVP) which is optimized for guided bronchoscopy, specifically with intraprocedural 3D image acquisition, that has the potential to minimize respiratory motion and atelectasis.

METHODS

Patient Population

Patients (n=50) referred for biopsy of PLLs by navigation bronchoscopy were included in this retrospective, IRB approved study with waiver of individual informed consent. All PLLs were characterized as peripheral nodules in that they were surrounded by normal aerated lung, none were visible endobronchially, and all were beyond the segmental bronchus so that all biopsies were transbronchial rather than endobronchial. All patients with pleural effusions, ascites, and diaphragmatic paralysis were excluded.

Two groups of 25 consecutive patients with PLLs <30 mm was included: In the first group, a conventional ventilation protocol was used during biopsy procedures between December 2017 and March 2018; in the second group, a dedicated LNVP was used during procedures between February and March 2020.

During the time period between the 2 cohorts, the LNVP ventilation strategy was formulated, refined and adopted by anesthesia colleagues as a ventilation protocol specifically for CBCT-guided bronchoscopic biopsy of peripheral lung nodules.

All patients were intubated with an 8.5 endotracheal tube. Total intravenous anesthesia with propofol and neuromuscular blocking agents (paralytics) were standard in both cohorts of patients. Each patient underwent CBCT imaging for procedural planning and guidance using a robotic c-arm system and iPilot software (Artis zeego, Siemens Healthineers, Forchheim, Germany). Once the catheter was aligned with the target PLL using CT augmented fluoroscopy, a needle was placed in the lesion and confirmation CBCT spin was performed. If adjustments were necessary, additional scans were performed. All CBCT imaging was performed using a 5 second protocol (248 projection images acquired at 0.8 degrees/projection) during an inspiratory breath hold at tidal volume, using a ventilation protocol as described below, and shown in Figure 2.

Navigation, Confirmation, and Biopsy

In each patient, the target lesion was highlighted in a process called segmentation, on the initial CBCT scan, for overlay on live fluoroscopic images. Subsequently, CT augmented fluoroscopy was used to navigate a steerable catheter (Edge Firm Tip, Medtronic, varying degrees) to the target lesion. Once the navigation catheter was optimally aligned, a biopsy tool was inserted and advanced to the lesion. Radial probe endobronchial ultrasound (rEBUS) was not used in any cases. CBCT was performed for tool-in-lesion confirmation to ensure that the biopsy tool was visible within the lesion, in 3 orthogonal planes (axial, sagittal and coronal). It was considered a center strike if the tool was in the middle third of the lesion in all views (Fig. 1). Rapid onsite pathologic evaluation was utilized in all cases.

F1
FIGURE 1:
Tool in lesion confirmation with tool with center strike through the middle one-third of the lesion in 3 orthogonal planes. Left to right: axial, coronal and sagittal multiplanar reformat views.

Conventional Ventilation Protocol

Conventional ventilation utilized continuous or standard intermittent mandatory ventilation (Fig. 2). Tidal volume, peak end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2), respiratory rate, tidal volume, and airway pressure valves were not subjected to any particular requirements. FiO2 was typically set at 100% FiO2 and PEEP was set to 0 or 5 cm H2O at the discretion of anesthesia

F2
FIGURE 2:
Flow charts demonstrating the Conventional (left) and lung navigation ventilation protocol (right) ventilation strategies. See text for details. APL indicates adjustable pressure-limiting; ETT, endotracheal tube; PEEP indicates peak end-expiratory pressure.

LNVP

A standard strategy for rapid intubation was utilized (not rapid sequence intubation) as shown in Figure 2. Patients with a previous history of lung resection, acute lung injury, or acute respiratory distress syndrome were excluded from LNVP.

After the patient recovered from any postinduction issues, such as hypotension, we lowered the FiO2 to the lowest tolerable FiO2. We employed 4 alveolar recruitment maneuvers. These maneuvers were hand-delivered via bagging the patient with 30 cm H2O over 30 seconds or 40 cm H2O over 40 seconds, although variability existed with the exact timing and pressures based on the anesthesiology personnel performing the maneuvers.

LNVP utilized a pressure control/volume guaranteed strategy, a dual ventilation strategy with pressure-controlled continuous mechanical ventilation and a patient-specified tidal volume. The volume guarantee ensured that all mandatory tidal volume was applied with the minimum pressure necessary.

Patients were placed on tidal volumes of 10 to 12 mL/kg of ideal body weight and specific PEEP settings based on the location of the lesion. Patients with lesions in the upper and middle lobes had PEEP set at 10 to 15 cm H2O. Patients with lower lobe lung lesions were placed on higher PEEP settings of 15 to 20 cm H2O to mitigate diaphragmatic motion (particularly in those with obesity) and atelectasis. The peak pressure limit was set to 45 cm H2O. Breath hold imaging techniques required the adjustable pressure-limiting (APL) valve on the anesthesia machine set at the same pressure as the PEEP.

Endpoints and Data analysis

Primary endpoints are dependent atelectasis, sublobar/lobar atelectasis and lesion obscured by atelectasis. Secondary endpoint is diagnostic yield as defined by the AQuIRE registry definition.

Determination of atelectasis was based on CBCT scans completed after navigation and once a biopsy tool was deployed (tool-in-lesion scan). Our decision to assess atelectasis at the CBCT tool-in-lesion scans was deemed a more appropriate time point than an initial CBCT scan following induction. We believed that at the time of the tool-in-lesion confirmation, the patient would be at highest risk of atelectasis. CBCT images were reviewed by 2 independent pulmonary critical care trained physician reviewers who were blinded to the subject and date of imaging. Dependent atelectasis is defined as any ground glass opacities at the dependent portions of the lung. Sublobar or lobar atelectasis is any consolidation. Obscured is partial or completely obscured lesion due to atelectasis. It is possible to have dependent ground glass atelectasis, sublobar/lobar atelectasis, and be obscured. Figure 3 demonstrates examples of atelectasis.

F3
FIGURE 3:
Definitions and examples of dependent, sublobar/lobar atelectasis and lesion obscured by atelectasis. All images were from patients who ventilated utilizing lung navigation ventilation protocol. A, Dependent atelectasis defined as any ground glass opacities at the dependent portions of the lung. Example demonstrates ground glass opacities in the dependent portion of the right lower lobe. B, Sublobar or lobar atelectasis defined as any form of consolidation. B, demonstrates consolidation in the right lower lobe. C, Obscured is partial or completely obscured lesion due to atelectasis. Example includes a tool-in-lesion image with an obscured right lower lobe lung lesion due to atelectasis. The yellow arrows point to areas of atelectasis.

Nodule size was determined by the largest diameter of the lesion on axial, coronal and sagittal images on the preplanning CT scan of the chest. Bronchus sign and location in the outer third of the lung periphery were also determined on the preprocedural CT scan.

Biopsy outcomes were evaluated on follow-up, using final pathology results, based on the strict definition used in the AQuIRE registry.13 All patients were subject to appropriate 2 year follow-up including serial CT scans, positron emission tomography/CT scans, CT guided needle and surgical biopsies. If lesions resolved, this was considered a true negative. If there was a lack of follow-up, the patient’s biopsy was considered a false negative or nondiagnostic. A diagnostic biopsy is a specific diagnosis made by bronchoscopy such as cancer or a specific benign diagnosis such as granulomatous disease, organizing pneumonia or specific pathogen. A nondiagnostic result was defined as normal lung tissue, blood, chronic inflammation, or atypical or suspicious cells. A false negative result was also considered nondiagnostic. For example, bronchoscopic biopsy demonstrates adenomatous hyperplasia but lobectomy demonstrates adenocarcinoma in situ. For each group, the diagnostic yield was computed by dividing the sum of total specific diagnosis made by bronchoscopy by the total number of lesions biopsied.4

Comparisons between ventilation protocol groups were made using unpaired Student t test for continuous variables and using the Fisher Exact test for nominal variables. Agreement between readers was assessed using the Cohen κ. Statistical analysis was performed using Microsoft Excel.

RESULTS

Patient demographics and lesion characteristics are summarized in Table 1. There were no statistically significant differences in any of the demographic variables. In each group the majority of subjects were female and tobacco users, and all but 1 subject were White. Two patients in the conventional ventilation group had 2 lesions; all other patients had 1 lesion each. Average lesion size was <20 mm for both groups, and lesions were significantly smaller in the LNVP group (15.7 vs. 19.3 mm, P=0.03). In addition, significantly more lesions were located in the distal one-third of the airways in the LNVP group (80% vs. 48%, P=0.02).

TABLE 1 - Demographic, Nodule, and Imaging Results for the Conventional and LNVP Groups
Conventional LNVP P
Demographics
 Age (y) 66.7 66.2 0.86
 Female sex 17 (68) 15 (60) 0.77
 White race* 24 (96) 25 (100) 1.00
 Tobacco use (current or former) 24 (96) 19 (76) 0.10
 BMI 26.6 25.5 0.54
Nodule characteristics
 Number of nodules 27 25
 Nodule size (mm) 19.3 15.7 0.03
 Nodule size <20 mm 13 (48) 19 (76) 0.05
 Upper lobe location 16 (59) 11 (44) 0.58
 Distal 1/3rd of lung 13 (48) 20 (80) 0.02
 Bronchus sign 19 (70) 10 (40) 0.05
Imaging/procedural results
 CBCT tool-in-lesion confirmation 23 (85) 25 (100) 0.11
 Center strike 5 (19) 9 (36) 0.22
 Diagnostic yield (%) 70 92 0.08
 Dependent atelectasis§ 0.0001
  R1 16 (64) 9 (36)
  R2 17 (68) 4 (16)
 Sublobar or lobar atelectasis§ 0.01
  R1 12 (48) 5 (20)
  R2 14 (56) 8 (32)
 Lesion obscured by atelectasis§ 0.0004
  R1 9 (36) 1 (4)
  R2 9 (36) 2 (8)
 Pneumothorax 0 1 (4) 1.00
Mean values are shown for continuous variables.
Significant P values are in bold.
Count (%) is shown for nominal variables.
*One patient in conventional ventilation group was African American.
Center strike was defined as the center one-third in 3 orthogonal views (axial, coronal, and sagittal) regardless of the nodule’s configuration.
Based on AQuIRE definition
§Results presented for Reader 1 (R1) and Reader 2 (R2). P values refer to differences between ventilation strategy.
Pneumothorax not requiring chest tube placement. Biopsy of right lower lobe pleural-based lesion.
BMI indicates body mass index; CBCT, cone beam computed tomography; LNVP, lung navigation protocol.

Imaging and procedural results are also shown in Table 1. Tool-in-lesion was confirmed in 3 orthogonal MPR planes for the vast majority of patients in both groups, with 100% tool-in-lesion in the LNVP group. Figures 4 and 5 contain representative images for patients in the conventional ventilation and LNVP groups; 3 patients from each ventilation group are included, with corresponding preprocedural multidetector CT images.

F4
FIGURE 4:
Images from 3 patients in the conventional ventilation group, showing location matched preprocedural helical CT images (left) and CBCT images at the time of tool in lesion confirmation attempt (right). Top row: right upper lobe lung nodule obscured by atelectasis and nondiagnostic. Middle row: dependent and sublobar atelectasis obscuring lung lesion was positive for carcinoid. Bottom row: dependent and sublobar atelectasis. Elevated diaphragm elevated due to a lack of PEEP. Biopsy was nondiagnostic.
F5
FIGURE 5:
Images from 3 patients in the LNVP group, showing location matched preprocedural helical CT images (left) and CBCT images at the time of tool in lesion confirmation (right). Top row: right lower lobe lung lesion positive for Cryptococcus. Middle row: left upper lobe lung nodule positive for metastatic melanoma. Bottom row: right upper lobe posterior lung lesion positive for adenocarcinoma.

Overall, atelectasis was more prevalent in the conventional ventilation group, as shown in Table 1 (P=0.0001 for dependent atelectasis; P=0.01 for sublobar/lobar atelectasis). For atelectasis, agreement between readers was good overall: κ=0.68 for dependent; κ=0.71 for sublobar/lobar. Examples of dependent and lobar/sublobar atelectasis are shown in Figure 3. The target lesion was obscured by atelectasis more often in the conventional ventilation group (P=0.0004), as shown in Table 1. For this variable, agreement between readers was excellent (κ=0.94). Atelectasis affected predominantly the lower lobes: in the conventional group, 19 of 33 (58%) affected lobes were lower, whereas for LNVP 12 of 17 (71%) affected lobes were lower (P=0.56 between groups).

Diagnostic yield was 70% for conventional ventilation and 92% for LNVP (P=0.08). Sensitivity and specificity were 78% and 100%, respectively, for conventional group; 100% and 100%, respectively, for LNVP. Positive predictive value was 100% for both patient groups; negative predictive value was 56% for conventional ventilation and 100% for LNVP.

As shown in Table 2, the conventional group had 19 diagnostic results, with 27 total lesions: 19/27=70%. There were 2 false-negative results, 1 with tool-in-lesion confirmation which demonstrated atypical adenomatous hyperplasia (CT-guided fine needle aspirate demonstrated adenocarcinoma in situ consistent with sampling error) and 6 nondiagnostic results with 3 tool-in-lesion confirmed. We considered the tool-in-lesion nondiagnostic result, “suspicious for small cell,” emphasizing how strict our definition of diagnostic yield and patient underwent stereotactic body radiation.

TABLE 2 - Conventional Ventilation Diagnostic Yield Analysis
Outcome Number Comment
Malignant 100% with CBCT tool in lesion confirmation
 Adenocarcinoma 9
 Carcinoid 2
 Non–small cell carcinoma 1
 Metastatic synovial sarcoma 1
 Metastatic breast cancer 1
Benign 100% with CBCT tool in lesion confirmation
 Filamentous bacteria 1 Resolved
 Non-necrotizing microgranulomas 3
 Organizing pneumonia 1
False negative 50% with CBCT tool in lesion confirmation
 Acute inflammation 1 No tool in lesion—positive lobectomy
 Adenomatous hyperplasia 1 Tool in lesion—positive for malignancy by CT-guided transthoracic needle aspiration
Nondiagnostic 25% with CBCT tool-in-lesion confirmation
 Normal lung tissue 1 No tool-in-lesion—patient lost to follow-up
 Anthracosis with scant lung tissue 1 No tool-in-lesion—enlarging on CT
 Intraparenchymal lymph node 1 No tool-in-lesion—stable
 Suspicious for small cell 1 Tool-in-lesion—SBRT and chemotherapy
 Chronic inflammation 2 Tool-in-lesion—residual scar
CT indicates computed tomography; CBCT indicates cone beam computed tomography; SBRT, stereotactic body radiation therapy.

As shown in Table 3, the LNVP group had 23 diagnostic results, with 25 total lesions: diagnostic yield of 23/25=92%. Both of the 2 false-negative results (100%) in this group had tool-in-lesion confirmation in 3 orthogonal planes on CBCT. These 2 false negatives with tool-in-lesion demonstrated suspicious malignant cells and both of these patients were treated with stereotactic body radiation.

TABLE 3 - Lung Navigation Ventilation Protocol Diagnostic Yield Analysis
Outcome Number Comment
Malignant 100% with CBCT tool-in-lesion confirmation
 Adenocarcinoma 7
 Squamous cell carcinoma 3
 Non–small cell lung cancer 3
 Melanoma 2
 Carcinoid 1
 Urothelial carcinoma 1
Benign 100% with CBCT tool-in-lesion confirmation
 Cryptococcus 1
 Aspergillus 1
 Granulomatous pneumonitis 1
  Organizing pneumonia 2
Mycobacteria avium complex 1
Nondiagnostic 100% with CBCT tool-in-lesion confirmation
 Suspicious for adenocarcinoma 1 SBRT
 Necrosis, suspicious for malignancy 1 SBRT
CBCT indicates cone beam computed tomography; SBRT, stereotactic body radiation therapy.

Each patient underwent 2 to 3 CBCTs per procedure (median=2). Procedural radiation exposure (dose area product) for the LNVP group was 7608±5032 μGym2 (mean±SD), with a median of 6535 μGym2 and range 1595 to 23556 μGym2. Radiation results were not available in picture archiving and commmunication system for the conventional ventilation group.

DISCUSSION

CT-to-body divergence including that caused by atelectasis and dynamic respiratory motion are major obstacles to successful peripheral lung navigation. A variety of methods and bronchoscopy platform innovations have attempted to mitigate CT-to-body divergence—including CBCT, digital tomosynthesis, optical pattern recognition, endoluminal visualization, and shape sensing devices—but lung ventilation strategies have yet to be fully evaluated.

Utilizing CBCT imaging or real time intraprocedural 3D imaging, bronchoscopists can see the effects of ventilation strategies on bronchoscopy. This study is one of the first to evaluate a strict LNVP for the purposes of bronchoscopic peripheral lung biopsies.14

Atelectasis

Of the many factors associated with lung ventilation during peripheral bronchoscopy, atelectasis represents one of the major obstacles, if not the most important obstacle, in navigation bronchoscopy. Casal et al,15 describe a small series of patients undergoing peripheral lung biopsies, where nearly 20% of the lesions were completely obscured by atelectasis as assessed by CBCT. The I-LOCATE trial also demonstrated in a prospective observational study that 89% of patients had atelectasis, as assessed by rEBUS; this trial identified BMI and time as the main factors contributing to atelectasis.16 In the current study, 36% of the patients with conventional ventilation strategy had lesions that were obscured by atelectasis. This surprising finding can render a bronchoscopic biopsy or marking of PLLs for thoracic surgical resection essentially futile. Therefore, strategies to safely reduce atelectasis are imperative to successful navigation. Even minor atelectasis with an upper lobe lesion subject to minimal respiratory motion can contribute to significant CT-to-body divergence. A target based on preprocedural imaging may be nowhere near the actual location of the lung lesion. Moreover, as we navigate to smaller lesions, the amount of divergence may be larger than the diameter of the lung lesion itself.

Once atelectasis occurs it can be difficult, if not impossible, to recruit atelectatic lung units. Several factors affect the ability to recruit atelectatic lung units, including surface tension, airflow and airways resistance.17 Surface tension is the force exerted by water molecules on the surface of the lung tissue as those water molecules pull together. Also, as the radius of the airways decreases, airways resistance increases. Turbulent airflow leads to further increase in airway resistance. These factors result in atelectatic lung units being at the wrong end of the compliance curve. Over-wedging the bronchoscope can unintentionally lead to focal atelectasis in the area of the biopsy. In our study, none of the lobar or sublobar atelectasis was due to overwedging of the scope. Notably, the LNVP arm demonstrated markedly reduced dependent atelectasis, sublobar/lobar atelectasis, and decreased obscured lesions compared with conventional ventilation strategy.

Fractional Inspired Oxygen and Reabsorption Atelectasis

Avoidance of high FiO2 (80% to 100%) is also critical to avoid absorption atelectasis. Multiple studies have established that absorption atelectasis occurs in the setting of 100% oxygen delivery in healthy anesthetized adults.18–23 Oxygen is rapidly absorbed and denitrogenation occurs leading to alveolar collapse.

Supraphysiologic concentrations of pure oxygen can also lead to type II alveolar epithelial injury by reactive oxygen species leading to impairment of surfactant production, pulmonary edema, and damage to cells. Of note, we routinely preoxygenated patients with 100% FiO2 for intubation and then rapidly titrated the FiO2 to lowest tolerable level (usually to 30% to 40%). While there is very little research to suggest the optimum FiO2, we recommend utilizing the lowest tolerable FiO2 to avoid absorption atelectasis while maintaining adequate procedural oxygenation for the patient.

Pressure Control Volume Guaranteed With High Tidal Volumes and PEEP Pressures

In the era of low lung volume strategies to reduce barotrauma and ventilator induced lung injury, we adopted a strategy counter to the traditional teaching of modern pulmonologists and anesthesiologists. For successful peripheral navigation to occur, the preprocedural CT should best correlate with the conditions during the actual procedure. Typically, CT scans are performed at the inspiratory reserve volume whereas procedural ventilation occurs at tidal volume. If atelectasis occurs, navigation will likely occur within the expiratory reserve volume. By increasing the tidal volume and PEEP, we expect better correlation with the preprocedural CT scan.

PEEP is important to maintain small airway patency in addition to its well known effects on the alveoli. If we employed zero end expiratory end pressure, we would cause injury to the alveoli through repeated volutrauma—opening and closing of alveoli. We deliberately chose higher levels of PEEP for lower lobe lung lesions to mitigate atelectasis. Obese patients in particular are at increased risk of atelectasis due to their lower FRC. Higher levels of PEEP were applied to patients with significant central obesity. For example, in patients with a BMI of 35 or greater, PEEP was set at 20 cm H2O for the biopsy of lesions in the dependent portions of the lungs. It is necessary to remain vigilant and always assess the hemodynamic effects of high PEEP. High PEEP can lead to hypotension and decreased oxygenation because of an impact on cardiac flow and compromised venous drainage. We did not note any significant barotrauma, pneumothorax or pneumomediastinum on any of the LNVP patients. We were not able to quantify the use pressors at the time of induction based on the medical records. If patients developed hypotension, it was treated and did not cause any significant delays or interruptions to the procedure. In all cases, patients tolerated the LNVP protocol well.

Although we did not utilize traditional navigational bronchoscopy, the importance of increased tidal volume and PEEP mitigating atelectasis is even more important for those reliant on a preprocedural CT scan for navigational bronchoscopy. Application of this protocolized ventilation strategy is generalizable to all patients undergoing peripheral bronchoscopy.

Breath Holding Strategies and the Adjustable Pressure Limit Valve

The advent of advanced image-guided navigation such as CBCT or fluoroscopic navigation with digital tomosynthesis (SuperDimension, Medtronic, Minneapolis, MN) has made the breath-hold procedure a critical component to navigational bronchoscopy. The real-time intraprocedural imaging requires breath hold strategies to reduce motion artifact. The APL valve should be set to the desired PEEP level to avoid excessive diaphragmatic motion. The APL valve (also referred to as an expiratory valve, relief valve or spill valve) is a type of flow control valve that will ensure the circuit will maintain airway pressure during breath-holding maneuvers where the anesthesia machine is changed to manual mode. It is also necessary to wait several seconds (usually 5 to 8 s) to allow for pressures in the ventilator circuit to equilibrate. This inspiratory pause will minimize motion artifact during intraprocedural imaging.

Navigation Versus Endobronchial Ultrasound (EBUS) First

In our experience, EBUS bronchoscopy, while important, can cause bloody secretions and promote atelectasis. The EBUS scope itself is larger (6.2 mm outer diameter or 73% of the diameter of an 8.5 mm endotracheal tube) and can contribute to overall decreased flow and promote dependent atelectasis. These changes, along with the time it takes to perform the procedure, lead to progressive changes that can negatively impact the procedure by worsening CT-to-body divergence.

CBCT imaging has allowed us to better understand the importance of pursuing navigation first. One can argue that a navigation first strategy allows the provider to obtaining additional tissue to accommodate for molecular heterogeneity, better assess mixed tumor types, reduce potential sampling error, or to offset lack of access to rapid onsite pathologic evaluation.

If there is a low pretest probability of malignant lymph nodes, we recommend that navigational bronchoscopy be done first. The downside risk of complications (ie, pneumothorax) with peripheral navigation in our opinion is low and the benefit outweighs the risk. The authors are confident as bronchoscopic CT imaging is more prevalent, there will be better recognition of the importance of navigation before EBUS bronchoscopy. The authors acknowledge further study is warranted.

Biopsy Strategies and Respiratory Motion

In the era of advanced imaging techniques, optimal biopsy should be performed when the target is aligned regardless of the presence of a bronchus sign. Alignment is a key strategy for successful biopsy. Deflection of the extended working channel/catheter caused by rigid biopsy tools can sometimes be used to your advantage to achieve optimal alignment. In other cases, the alignment may be so precarious that any deflection, by even the most malleable of tools, will cause misalignment. The bronchoscopist may also choose to biopsy during a breath hold (inspiratory or expiratory), or biopsy throughout the active respiratory cycle.

It may be helpful to assess the PLL’s position with rEBUS throughout the respiratory cycle. If the rEBUS image moves in sync or independently, this can be helpful in deciding the optimal timing for biopsy.

Tool-in-Lesion Confirmation Rate and Diagnostic Yield

Comparing diagnostic rates of various technologies has been challenging given the heterogeneity of definitions such as the NAVIGATE definition, AQuIRE registry definition, and other paper’s specific definitions. Use of rEBUS to confirm lesion localization may not always provide an accurate measure of lesion localization. rEBUS accuracy may be confounded by atelectasis and hemorrhage.10 rEBUS can also only provide a lateral view and not a forward-looking view; thus, rEBUS cannot determine the directionality of the lesion.

Alternatively, CBCT imaging offers ground truth as to the actual location of the biopsy tool and its relationship to the primary lesion. We report CBCT tool-in-lesion confirmation as to whether the biopsy tool is in the lesion in 3 orthogonal planes. Contact with a lesion as reported by Verhoeven et al5 means that the needle was in contact but not necessarily in the lesion. CBCT tool-in-lesion confirmation is a higher bar of confirmation that provides increased confidence in the biopsy attempt. CBCT tool-in-lesion rate for the conventional group was 23/27 patients (85%) and the LNVP group was 100%. The negative predictive value of the conventional group and LNVP was, 56% and 100%, respectively. The improved negative predictive value raises confidence. In turn, the improved negative predictive value would ideally lead to less invasive follow-up biopsies. One recent study demonstrated the probability of more invasive biopsy, such as CT-guided needle biopsy or thoracoscopic surgery in case of a nondiagnostic bronchoscopy or bronchoscopy with bronchial genomic classifier ranges from 53% to 61%.23 If confidence is high based on CBCT tool-in-lesion confirmation and a high negative predictive value, these patients can proceed with serial imaging instead and avoid unnecessary invasive biopsy.

We chose to use the AQuIRE registry definition as it is more stringent in its assessment of biopsies. We noted a trend toward improved diagnostic yield: 70% for the conventional ventilation group and 92% for the LNVP cohort, but the difference was not statistically significant.

Lastly, the discrepancy between CBCT tool-in-lesion confirmation and false-negative results can be explained by inadequacy of tissue acquisition. It also may offer insight as to whether the lesion is pauci-cellular or necrotic. As with linear EBUS, there are instances when the needle is in the lymph node, but the sample is still nondiagnostic. The same can be true with the biopsy of PLL, including percutaneous biopsies done with CT guidance.

Limitations

This study has several limitations. All procedures and measurements were performed by a single physician at a single center, which limits the generalizability of the findings and introduces the possibility of selection bias. There was no preselected risk calculator which could help reduce bias.

We performed 30 CBCT-guided bronchoscopy procedures before conventional ventilation group and over 300 CBCT-guided bronchoscopy procedures before the LNVP group. The authors recognize that experience may have contributed to improved diagnostic yield, biopsy of smaller lung nodules, less bronchus signs, and more PLL. We also recognize that the ability to go after more challenging lesions was predicated on the ability to control for ventilation, reduce CT-to-body divergence and thereby ensure better accuracy of the CT augmented fluoroscopic overlay.

LNVP variability existed in terms of timing/methods of PEEP recruitment, PEEP and APL settings and determination of volumes. The protocol allowed parameters for flexibility based on the patient’s obesity, height, sex, and location of PLL. This may limit generalizability.

Multicenter studies with multiple operators and larger number of patients using the same navigational ventilation protocol in a prospective trial would be helpful.

CONCLUSIONS

Our experience highlights an aspect of navigational bronchoscopy that requires further study. Protocolized ventilation strategies can be employed safely to reduce atelectasis, minimize CT-to-body divergence, and limit excessive respiratory motion. In one aspect, while we have often focused on the technologies including rEBUS, navigation platforms, and tools, we have not until recently recognized the importance of specific ventilation strategies for guided bronchoscopy. We feel that these techniques could positively influence the overall success of navigational bronchoscopy. The authors agree that different ventilation protocols can be successful.

Understandably, it is rare that bronchoscopists have access to such advanced imaging technologies such as CBCT. Nonetheless, we are able to offer unique insight into the effects of various ventilation strategies on the outcome of navigational bronchoscopy procedures.

ACKNOWLEDGMENT

The authors thanks Michael Lorren, CRNA for significant contributions to the LVNP protocol.

REFERENCES

1. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: one-year results of the prospective multicenter NAVIGATE Study. J Thorac Oncol. 2019;14:445–458.
2. Wang Memoli JS, Nietert PJ, Silvestri GA, et al. Meta-analysis of guided bronchoscopy for the evaluation of the pulmonary nodule. Chest. 2012;142:385–393.
3. Gex G, Pralong JA, Combescure C. Diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules: a systematic review and meta-analysis. Respiration. 2014;87:165–176.
4. Pritchett MA, Schampaert S, de Groot JAH, et al. Cone-beam CT with augmented fluoroscopy combined with electromagnetic navigation bronchoscopy for biopsy of pulmonary nodules. J Bronchol Interv Pulmonol. 2018;25:274–282.
5. Verhoeven RLJ, Fütterer JJ, Hoefsloot W, et al. Cone-beam CT image guidance with and without electromagnetic navigation bronchoscopy for biopsy of peripheral pulmonary lesions. J Bronchol Interv Pulmonol. 2021;28:60–69.
6. Aboudara M, Roller L, Rickman O, et al. Improved diagnostic yield for lung nodules with digital tomosynthesis-corrected navigational bronchoscopy: initial experience with a novel adjunct. Respirology. 2020;25:206–213.
7. Sagar AS, Sabath BF, Eapen GA, et al. Incidence and location of atelectasis developed during bronchoscopy under general anesthesia: the I-LOCATE trial. Chest. 2020;158:2658–2666.
8. Pritchett MA, Bhadra K, Calcutt M, et al. Virtual or reality: divergence between preprocedural computed tomography scans and lung anatomy during guided bronchoscopy. J Thorac Dis. 2020;12:1595–1611.
9. Rojas-Solano JR, Ugalde-Gamboa L, Machuzak M. Robotic bronchoscopy for diagnosis of suspected lung cancer: a feasibility study. J Bronchology Interv Pulmonol. 2018;25:168–175.
10. Herth FJ, Eberhardt R, Sterman D, et al. Bronchoscopic transparenchymal nodule access (BTPNA): first in human trial of a novel procedure for sampling solitary pulmonary nodules. Thorax. 2015;70:326–332.
11. Ali EAA, Takizawa H, Kawakita N, et al. Transbronchial biopsy using an ultrathin bronchoscope guided by cone-beam computed tomography and virtual bronchoscopic navigation in the diagnosis of pulmonary nodules. Respiration. 2019;98:321–328.
12. Hogarth DK. Use of augmented fluoroscopic imaging during diagnostic bronchoscopy. Future Oncol. 2018;14:2247–2252.
13. Ost DE, Ernst A, Lei X, et al. Diagnostic yield and complications of bronchoscopy for peripheral lung lesions. results of the AQuIRE registry. Am J Respir Crit Care Med. 2016;193:68–77.
14. Hohenforst-Schmidt W, Banckwitz R, Zarogoulidis P, et al. Radiation exposure of patients by cone beam CT during endobronchial navigation—a phantom study. J Cancer. 2014;5:192–202.
15. Casal RF, Sarkiss M, Jones AK, et al. Cone beam computed tomography-guided thin/ultrathin bronchoscopy for diagnosis of peripheral lung nodules: a prospective pilot study. J Thorac Dis. 2018;10:6950–6959.
16. Doyle DJ, O’Grady KF Hagberg C. Physics and modeling of the airway. Benumof and Hagberg’s Airway Management. Philadelphia, PA: Elsevier Saunders; 2013:92–117.
17. Strandberg A, Tokics L, Brismar B, et al. Constitutional factors promoting development of atelectasis during anaesthesia. Acta Anaesthesiol Scand. 1987;31:21–24.
18. Klingstedt C, Hedenstierna G, Lundquist H, et al. The influence of body position and differential ventilation on lung dimensions and atelectasis formation in anaesthetized man. Acta Anaesthesiol Scand. 1990;34:315–322.
19. Rothen HU, Sporre B, Engberg G, et al. Prevention of atelectasis during general anaesthesia. Lancet. 1995;345:1387–1391.
20. Neumann P, Rothen HU, Berglund JE, et al. Positive end-expiratory pressure prevents atelectasis during general anaesthesia even in the presence of a high inspired oxygen concentration. Acta Anaesthesiol Scand. 1999;43:295–301.
21. Tokics L, Hedenstierna G, Strandberg A, et al. Lung collapse and gas exchange during general anesthesia: effects of spontaneous breathing, muscle paralysis, and positive end-expiratory pressure. Anesthesiology. 1987;66:157–167.
22. Habre W, Petak F. Perioperative use of oxygen: variabilities across age. Br J Anaesth. 2014;113(suppl 2):ii26–ii36.
23. Feller-Kopman D, Liu S, Geisler BP, et al. Cost-effectiveness of a bronchial genomic classifier for the diagnostic evaluation of lung cancer. J Thorac Oncol. 2017;12:1223–1232.
Keywords:

electromagnetic navigation bronchoscopy; cone-beam computed tomography; tomosynthesis; fluoroscopic navigation; ventilation; lung cancer

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.