Version May 2024
INTRODUCTION — Peripheral pulmonary nodules or lesions (PPLs; also known as peripheral lung lesions [PLLs]) are difficult to biopsy using a conventional flexible bronchoscope. Several image-guided bronchoscopy (IGB) techniques are available for the biopsy of PPLs.
This review discusses the use of IGB techniques in the diagnosis of PPLs. The general management of patients with a solitary pulmonary nodule, the types, indications, contraindications, and procedures associated with conventional flexible bronchoscopy are provided separately. (See "Diagnostic evaluation of the incidental pulmonary nodule" and "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Associated diagnostic and therapeutic procedures" and "Flexible bronchoscopy in adults: Indications and contraindications".)
EPIDEMIOLOGY OF PERIPHERAL PULMONARY LESIONS — The incidence of PPLs in the general population is unknown. Lung cancer computed tomographic (CT) screening studies of smokers at high risk for malignancy report a prevalence of nodules as high as 50 percent, with other CT studies in the general population reporting a prevalence of incidental nodules at 31 percent [1]. (See "Screening for lung cancer".)
The incidence of PPLs detected by CT will likely increase in the future. There are an estimated 10 to 12 million CT scans of the chest performed per year in the United States and low-dose CT scans are being increasingly performed for lung cancer screening [2-4]. In addition, newer generation CT scanners can detect very small pulmonary lesions not readily visible on older generation CT scanners. Thus, an increasing need for image-guided bronchoscopic (IGB) modalities capable of obtaining tissue safely from such lesions is predicted.
DEFINITION AND ETIOLOGY OF PERIPHERAL PULMONARY LESIONS — A PPL (also known as peripheral lung lesion [PLL]) is a pulmonary nodule (typically <3 cm) that is located in the lung periphery. It can be solid or subsolid, benign or malignant (table 1), and in general is traditionally hard to biopsy using conventional flexible bronchoscopy. A more detailed definition and etiology of solitary pulmonary nodules (SPNs) are discussed in detail separately. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Definitions' and "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Differential diagnosis'.)
INDICATIONS
Biopsy of peripheral pulmonary lesion — Image-guided bronchoscopy (IGB) techniques are most commonly used to biopsy PPLs since the diagnostic yield of conventional bronchoscopy is poor for such lesions. This indication is the focus of this topic. (See 'Image-guided bronchoscopy techniques' below and "Flexible bronchoscopy in adults: Associated diagnostic and therapeutic procedures".)
While some of the IGB techniques are capable of providing guidance to central lymph nodes or masses (ie, close to major airways), this is not typically done due to the excellent yield and relative ease of performing convex probe endobronchial ultrasound transbronchial needle aspiration (CP-EBUS-TBNA) for central lesions, the details of which are discussed separately. (See "Endobronchial ultrasound: Technical aspects", section on 'Lymph nodes'.)
Marking the position of peripheral pulmonary lesion — Therapeutic applications of IGB techniques are uncommon. These include the following:
●Fiducial marker placement – IGB techniques can be used to place fiducial markers (ie, a marker that can be imaged) into peripheral pulmonary malignancies so that stereotactic ablative radiotherapy can be delivered in a targeted fashion.
●Tattooing – Since small PPLs are sometimes hard to identify manually, tattooing a PPL with dye or contrast agent preoperatively with IGB techniques can facilitate visual localization of the PPL in the operating room at the time of surgical resection [5].
Investigational — IGB techniques are also being investigated in malignant pulmonary nodules to deliver therapeutic tools such as cryotherapy, brachytherapy, radiofrequency ablation, and microwave ablation directly at the nodule location. (See "Bronchoscopic cryotechniques in adults" and "Endobronchial brachytherapy".)
CONTRAINDICATIONS
General — Contraindications to image-guided bronchoscopy (IGB) are essentially the same as standard flexible bronchoscopy (eg, coagulopathy, hemodynamic instability). In addition, their use is limited to centers with skilled expertise. (See "Flexible bronchoscopy in adults: Indications and contraindications", section on 'Contraindications'.)
Specific — One relative contraindication unique to IGB is the use of electromagnetic navigation bronchoscopy (ENB) and some robotic bronchoscopy (RB) systems in the setting of cardiac pacemakers and defibrillators. The presence of a pacemaker or defibrillator has been considered a relative contraindication to IGB techniques that involve the use of an electromagnetic field due to concerns that pacemaker or defibrillator function could be affected. However, a study of 24 patients with pacemakers and defibrillators who underwent ENB reported that none of the patients suffered any arrhythmia or disruption of pacemaker function and that the procedure was safely completed in all patients [6]. Additional data in larger series are required to confirm these findings. Although practice among institutions is variable, we typically consult with cardiology subspecialty experts to determine whether settings need to be changed prior to the procedure; following ENB, we also have the pacemaker interrogated to make sure that the device is functioning properly. (See 'Electromagnetic navigation bronchoscopy' below.)
These techniques do not require contrast such that allergies to contrast are not a contraindication.
IMAGE-GUIDED BRONCHOSCOPY TECHNIQUES — Several image-guided bronchoscopy (IGB) techniques are available to assist in the biopsy of PPLs. In general, the use of these techniques is limited to centers with expertise, and they require specific training for their use. The diagnostic yield ranges from 44 to 88 percent, typically varying with lesion size, location, and equipment used as well as other factors including the presence of a bronchus sign and biopsy technique.
Virtual bronchoscopy — Virtual bronchoscopy (VB) is a noninvasive form of bronchoscopy. It is not an endoscopic procedure, but rather an imaging modality that uses non-contrast-enhanced CT images to reconstruct the airways in a three-dimensional manner producing images that appear similar to those visualized during invasive bronchoscopy. While VB itself cannot acquire samples, it can be used to preplan future procedures or as a navigational tool for biopsy (VBN). Further details regarding VB are provided separately. (See "Flexible bronchoscopy in adults: Overview", section on 'Virtual bronchoscopy' and 'Virtual bronchoscopic navigation' below.)
Navigation bronchoscopy — Navigation bronchoscopy (NB) uses a navigational system to guide instruments (eg, flexible or ultrathin bronchoscope) through the airways to a target lesion for biopsy. Navigational systems can be virtual (VBN; usually non-contrast-enhanced CT) or electromagnetic (ENB). ENB is the most common IGB technique used to biopsy PPLs.
Virtual bronchoscopic navigation
Technique — Virtual bronchoscopic navigation (VBN; also known as virtual navigational bronchoscopy [VNB]) is a technique that utilizes VB CT imaging to guide the bronchoscope to a peripheral target lesion in the lung (figure 1).
●Planning phase – First, CT scan images are acquired with a specialized CT protocol and transferred to a computer workstation where specific software is used to create a virtual bronchoscopic pathway to the target lesion. It is done usually on the same day or a few days ahead of the planned biopsy procedure. (See 'Virtual bronchoscopy' above.)
●Guidance phase – During the guidance phase, the acquired virtual images of the airway pathway are displayed and synchronized with real-time images from the bronchoscope (flexible or ultrathin bronchoscope) or until the target lesion is reached. This allows the bronchoscope to be advanced branch-by-branch through the airway to the target lesion.
●Biopsy phase – Depending on the procedure chosen to biopsy the lesion, a PPL can be sampled:
•Flexible bronchoscopy or ultrathin bronchoscopy:
-Standard brush and biopsy forceps equipment can be placed through the working channel of these scopes to obtain samples from a PPL with or without additional fluoroscopic guidance. Ultrathin bronchoscopes are limited by the size of the working channel. (See "Flexible bronchoscopy in adults: Associated diagnostic and therapeutic procedures", section on 'Diagnostic' and 'Ultrathin bronchoscopy' below.)
-Radial endobronchial ultrasound probes (RP-EBUS) can be placed with a guide sheath through the working channel of a flexible bronchoscope so that the target nodule can be visualized and its location confirmed. The EBUS probe is then removed and the guide sheath left in place and PPL sampled using standard equipment (with or without fluoroscopy). (See 'Radial probe endobronchial ultrasound (RP-EBUS)' below and "Endobronchial ultrasound: Technical aspects", section on 'RP-EBUS-guided transbronchial biopsy'.)
Several commercially available systems are available. The accuracy of these systems depends upon the quality of the CT data; thus, thin-slice CT scan data and recent CT data from VB-specific protocols are preferred.
Among the available systems, none incorporate real-time tracking of instruments during the navigation procedure and therefore do not confirm the location of the operating instrument or visualize the target nodule. Thus, RP-EBUS and fluoroscopy can all be used in conjunction with VBN to increase the chances of biopsying the target PPL. (See "Flexible bronchoscopy in adults: Associated diagnostic and therapeutic procedures" and 'Ultrathin bronchoscopy' below.)
Efficacy — The diagnostic yield from VBN has only been reported from centers with expertise and ranges from 67 to 80 percent:
●A pooled analysis of 13 studies reported an overall diagnostic yield of 74 percent for procedures utilizing VBN assistance to biopsy PPLs [7]. The yield for lesions ≤2 cm in size was lower (67 percent). In many cases EBUS and fluoroscopy were used in conjunction with VBN.
●A large meta-analysis of 39 studies, many of which used VBN in conjunction with other IGB techniques reported a similar diagnostic yield of 72 percent [3].
●Two randomized clinical trials of VBN- versus non-VBN-assisted techniques for PPLs showed mixed results with one reporting increased diagnostic yield (80 versus 67 percent) and the other showing no difference (67 versus 60 percent) [8,9].
Electromagnetic navigation bronchoscopy
Technique — Electromagnetic navigation bronchoscopy (ENB) incorporates VB imaging with an additional navigational tool, an electromagnetic field (figure 2).
●The planning phase – Thin slice CT data are used to generate a VB pathway to the peripheral lesion similar to that described above (see 'Technique' above). The software suggests the best pathway which can be selected by the operator, alternatively, a different pathway can be chosen than that suggested by the ENB system, which can then be modified or changed by the operator in the planning phase (figure 3).
●The guidance and biopsy phase – Prior to the procedure, an electromagnetic field board or generator is placed under the patient's thorax or adjacent to the patient, which allows for real-time tracking of instruments during the procedure.
•In one commercially available system, a locator guide catheter, which can be tracked in the electromagnetic field by the system, is placed through a steerable sheath. The guide and sheath together are placed through the working channel of the flexible bronchoscope and are advanced together in real time based on the computers provided guidance of direction and distance (similar to a global positioning system for vehicles) until the target lesion is reached. The PPL is then biopsied using:
-ENB alone – Once the lesion is reached, the ENB locator guide is removed and the working guide sheath is left in place through which standard biopsy instruments can be passed (eg, brush, transbronchial biopsy [TBBX]) to obtain a sample. TBBX and brushing procedures are the same as those described for routine flexible bronchoscopy (with or without fluoroscopy). (See "Flexible bronchoscopy in adults: Associated diagnostic and therapeutic procedures".)
Some studies report that using a catheter aspiration (also known as catheter suctioning) technique is superior to the traditional forceps biopsy of peripheral lung lesions [10]. This involves instilling a small amount of fluid through the sheath and then aspirating the fluid back.
-ENB is often performed in conjunction with other IGB techniques, including RP-EBUS – Importantly, ENB cannot directly visualize the target lesion such that the PPL location cannot be confirmed nor can it be biopsied under direct visualization. Thus, when available, some experts combine ENB with RP-EBUS to verify the lesion location which may increase the diagnostic yield for PPL biopsy. The RP-EBUS probe is passed through the working guide sheath, the PPL location is confirmed, the probe removed, and the lesion is biopsied as for routine flexible bronchoscopy (with or without fluoroscopy). (See 'Efficacy' below and 'Radial probe endobronchial ultrasound (RP-EBUS)' below.)
•Another commercially available system also uses CT data to generate a virtual three-dimensional pathway to the selected target and electromagnetic tracking of a steerable working channel with sensors on the tip or by using a trackable biopsy instrument during the procedure. Experience with this system is more limited. This system also incorporates an option for transthoracic needle aspiration or biopsy (TTNA/TTNB) using the same electromagnetic and CT guidance data with a trackable percutaneous needle. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Transthoracic needle biopsy'.)
In some specialized centers, cone-beam CT can also be used similar to RP-EBUS to confirm that the biopsy instruments are within the target PPL. The capital costs for ENB systems are high, and significant operator experience and training are required for their use.
Efficacy — ENB accounts for the majority of clinical experience and published literature of all IGB techniques. ENB is endorsed by the American College of Chest Physicians' clinical practice guidelines for evaluation of patients with pulmonary nodules at intermediate risk of malignancy, the details of which are discussed separately [11,12]. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Nonsurgical biopsy' and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Enhanced, image-guided bronchoscopic techniques'.)
Although large randomized trials are lacking, ENB has a similar yield to other IGB techniques, ranging from 44 to 75 percent (average approximately 65 percent) [3,10-19]. Most trials utilized the same commercially available system, and analysis is limited by methodological flaws including retrospective design, small sample size, and variations in IGB techniques employed to biopsy nodules of varying size and location.
●In a systematic review of 15 trials that included a total of 1033 peripheral lung nodules, a definitive diagnosis was obtained in 65 percent of ENB-guided biopsy procedures [14]. Variables associated with a higher yield included larger nodule size (>2 cm), upper or middle lobe location, lower registration error (ie, more accurate matching of the virtual CT data to the real-time airway anatomy in the electromagnetic field), combined use with RP-EBUS, presence of a bronchus sign leading into the lesion, and sampling the lesion with a catheter suctioning technique. A better yield with the use of rapid on-site cytologic evaluation (ROSE) as well as the use of general anesthesia were also reported. (See 'Technique' above and 'Radial probe endobronchial ultrasound (RP-EBUS)' below and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Endobronchial ultrasound'.)
●In a meta-analysis that included 11 ENB studies, the diagnostic yield of ENB was similarly reported at 67 percent [3]. Most studies utilized ENB alone without the addition of RP-EBUS.
●One study demonstrated a superior yield when ENB was combined with RP-EBUS (88 percent) compared with ENB alone (59 percent) or EBUS alone (69 percent) [13]. Results were similar when the analysis was restricted to small nodules measuring 2 cm in diameter. Other studies demonstrated similar results [10,20].
●A large international prospective cohort study using ENB (NAVIGATE) enrolled 1215 patients, and tissue was obtained in 94 percent of those who had ENB completed. The majority of lesions were in the peripheral/middle one-third of the lung with a median lesion size of 20 mm. Radial EBUS was used in 57 percent and fluoroscopy in 91 percent of procedures. ENB-specific procedure time was 25 minutes. Follow-up was completed in 99 percent of patients at one month and in 80 percent at 12 months. The ENB pneumothorax rate was 5 percent [21]. The 12-month diagnostic yield was 73 percent. Pathology results of the ENB-aided tissue samples showed malignancy in 44 percent. ENB-related grade 2 or higher pneumothoraces (requiring admission or chest tube placement) occurred in 2.9 percent. The ENB-related bronchopulmonary hemorrhage rate was 1.5 percent and respiratory failure rate was 0.7 percent.
Another available ENB system utilizes “tip tracked” instruments such that the biopsy needle, forceps, or brush are tracked in the electromagnetic field in real time. This same system also offers the option for electromagnetic-guided transthoracic needle biopsy (ETTNA).
●A pilot study of this system is limited to a single report in 24 patients undergoing lymph node sampling for lung cancer staging that compared ETTNA with other navigational systems and/or EBUS [22]. The overall diagnostic yield for the techniques tested was 72 percent (NB alone), 83 percent (ETTNA alone), 87 percent (NB plus ETTNA), and 97 percent (ETTNA plus NB plus EBUS). Additional larger studies will be needed to further evaluate this ENB/TTNA system.
●A larger study evaluated the safety and diagnostic performance of this same ETTNA system as performed by pulmonologists. This was a retrospective, multicenter study of 129 electromagnetic-guided percutaneous lung biopsies with an average age of participants of 65.6 years and a body mass index of 26.3. The majority of lesions were in the right upper lobe (37.2 percent) and left upper lobe (31.8 percent). The mean size of the lesions was 27.31 mm, and the average distance from the pleura was 13.2 mm. There were 17.8 percent pneumothoraces, of which 12.4 percent received small-bore chest tube placement. Diagnostic yield was 73.7 percent, and when ENB-guided bronchoscopic sampling was also performed during the same procedural encounter, the overall diagnostic yield increased to 81.1 percent [23].
Robotic bronchoscopy — The newest form of IGB involves the use of robotic bronchoscopy (RB) platforms to reach PPLs. There are currently two systems in commercial use that use the following principles:
●The planning phase – The systems require thin-slice CT scan data to plan the pathway and navigate to the desired target. One system utilizes an electromagnetic field similar to ENB.
●The guidance and biopsy phase – These systems use a small robotic endoscope controlled by robotic steering devices under direct visualization or other unique technology driven by the operator. Both systems utilize differing technology platforms but overall have the advantages of more precise articulation and control of the bronchoscope and the ability to maintain a fixed position once the target PPL is reached. The bronchoscopes are advanced and steered using a separate control device so the operator is not actively touching the bronchoscope. The instrument working channels are similar to those of a standard adult flexible bronchoscope.
Theoretic advantages of such technology include continuous endobronchial visualization and greater maneuverability of the tip of the bronchoscope with the ability to lock into a desired position. Neither system offers tactile feedback to the operator and one system does not offer actual visualization at the time of biopsy.
Several studies support feasibility [24-27]:
●A feasibility study of 15 PPLs with a median size of 2.6 cm showed one system to successfully obtain biopsies in 93 percent [24]. Twelve lesions were peripheral and three were central. Radial EBUS was not used to confirm location. There was no pneumothorax and no significant bleeding.
●Another small study published in abstract format of 30 patients used a different robotic system to reach PPLs with a mean diameter of 12.5 mm and obtained a diagnostic yield of 83 percent. There were no significant complications [25].
●A prospective multicenter trial (BENEFIT) of 55 patients with PPL using RB examined a primary endpoint of localization of the PPL by RP-EBUS and adverse events. The study utilized RB plus RP-EBUS and fluoroscopy. Localization was achieved in 96 percent with diagnostic yield in 74 percent. A concentric RP-EBUS view was seen in 61 percent and eccentric view in 39 percent of lesions. Pneumothorax occurred in 3.7 percent and yield was higher in malignant lesions (82.5 percent). A larger trial of an estimated 1200 patients is underway [28].
●Another large multicenter trial using a different RB system included 241 patients with 270 PPLs (largest mean measurement, 18.8±6.5 mm) [27]. The mean time to navigate to the PPL decreased from 10 minutes in the first 10 cases to 7 minutes in subsequent cases. Adequate tissue was obtained in 96 percent. Diagnostic yield was not measured. Pneumothorax occurred in 3.3 percent, and airway bleeding in 0.8 percent.
Radial probe endobronchial ultrasound (RP-EBUS)
Technique — RP-EBUS comprises a miniature (20 or 30 MHz) ultrasound probe that can fit through the working channel of a flexible bronchoscope to provide a 360 degree view of the lung parenchyma (picture 1 and figure 4). Its small size allows it to extend distally into subsegmental bronchi so that PPLs can be visualized.
RP-EBUS is itself not a navigational tool; rather, it is typically used as an adjunctive imaging tool to confirm that the lesion has been reached. It can be used with the following biopsy modalities:
●Standard flexible bronchoscopy with or without a designated guide sheath (also known as RP-EBUS-GS). (See "Endobronchial ultrasound: Technical aspects", section on 'RP-EBUS-guided transbronchial biopsy'.)
●CT reconstruction with bronchoscopic fluoroscopy.
●Navigational techniques, including ENB or RB. The technique used to biopsy lesions using RP-EBUS and ENB combined is similar to that described for standard flexible bronchoscopy. In brief:
•The ENB or RB system is advanced towards the target PPL, as described above. (See 'Technique' above.)
•The radial EBUS probe is then passed through the working channel of the ENB or RB system.
•The PPL is visualized in real time as demonstrated in an ultrasound image, thereby confirming the accuracy of the navigation.
•Once the PPL is visualized, the radial EBUS probe is removed and biopsy instruments are placed through the working channel of the ENB or RB system to obtain tissue, as described above. (See 'Technique' above.)
Notably, RP-EBUS is the only IGB tool other than CT fluoroscopy that can provide real-time visualization of the lesion prior to biopsy. However, RP-EBUS cannot provide actual real-time biopsy visualization as the probe must be removed from the sheath in order to pass the biopsy instruments.
Equipment costs are typically less expensive than those of ENB systems, but a significant learning curve is required in the navigation of the radial probe and in the interpretation of peripheral pulmonary ultrasound imaging. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Endobronchial ultrasound' and "Endobronchial ultrasound: Technical aspects", section on 'Parenchymal lesions'.)
Efficacy — The diagnostic yield of RP-EBUS-guided biopsy of PPLs ranges from 58 to 88 percent. However, trials that study the efficacy of RP-EBUS are limited by methodologic flaws including variable use of EBUS with or without other navigational tools (eg, CT, ENB, fluoroscopy) and heterogeneity of nodule characteristics (large, small, central, and peripheral lesions).
●In a large meta-analysis of IGB techniques, the diagnostic yield of RP-EBUS-assisted techniques was 70 percent [3]. Some of these studies combined RP-EBUS with ENB, ultrathin bronchoscopy, or virtual bronchoscopy. Other meta-analyses have suggested similar results with significant heterogeneity among studies [29].
●A retrospective review of 467 patients in whom RP-EBUS was used as the only IGB technique (ie, without navigational or virtual assistance) to biopsy peripheral nodules reported an overall diagnostic yield of 69 percent [30]. Only 4 percent of the nodules could not be visualized and the diagnostic yield increased with nodule size: 1 to 2 cm (58 percent); 2.1 to 3 cm (72 percent); 3.1 to 4 cm (77 percent); 4.1 to 5 cm (87 percent); and >5 cm (88 percent). Procedures were performed with the RP-EBUS guide sheath in 60 percent of procedures and the metal directional curette and fluoroscopy in 35 percent. Of note, the diagnostic yield was 84 percent with the probe/sheath within the PPL and 48 percent when the probe/sheath was adjacent to the PPL.
●A systematic review of 16 studies totaling 1420 patients with PPLs, reported that RP-EBUS had a sensitivity for the diagnosis of lung cancer of 73 percent. The sensitivity was unchanged when RP-EBUS was performed alone and was not altered by the use of a guide sheath [31].
●In one retrospective study, CT-anatomic reconstruction images from multiplanar CT (available for most physicians) performed prior to bronchoscopy were used together with fluoroscopy and radial EBUS performed during bronchoscopy for diagnostic biopsy of PPLs, half of which were <2 cm [32]. The location was confirmed in 95 percent of cases, and the overall diagnostic yield with this approach was almost 60 percent.
Other
Fluoroscopic-guided bronchoscopy — Routine transbronchial biopsy may be performed blindly or using fluoroscopy. One systematic review of 18 studies reported a higher diagnostic yield with fluoroscopic-guided transbronchial needle aspiration when compared with blind transbronchial biopsy (60 versus 45 percent) [33]. The presence of the CT bronchus sign, large malignant lesions (>3 cm), and the employment of ROSE predicted a higher yield with fluoroscopy guidance.
CT bronchoscopy — Compared with conventional fluoroscopy, high-resolution three-dimensional CT imaging during flexible or ultrathin bronchoscopy can provide real-time images to guide the bronchoscope/instruments directly into the target lesion so they can be biopsied under direct CT guidance. The CT image is used to show that the biopsy instrument is in the lesion. However, this technique is not widely used due to difficulty with scheduling access to CT scanning suites and significant radiation exposure.
A few studies of CT-guided bronchoscopy have reported yields of 65 to 73 percent for pulmonary nodules [34-36]. One randomized trial of conventional bronchoscopy versus CT-guided bronchoscopy for the diagnosis of lung cancer in peripheral lesions and lymph nodes demonstrated no significant difference in diagnostic yield (71 versus 76 percent) [36]. Similar diagnostic yields have been reported when using a low-dose CT protocol, which minimizes radiation exposure [35].
Ultrathin bronchoscopy — Ultrathin bronchoscopes are smaller variants of a flexible bronchoscope ranging in diameter from approximately 2.8 to 3.5 mm (picture 1). Compared with a standard flexible bronchoscope, the smaller size of ultrathin bronchoscopes allows for better maneuverability and greater ability to reach much smaller airways beyond the typical reach of conventional bronchoscopes (ie, beyond the second or third order) (figure 5). Ultrathin bronchoscopy (UTB) is not a form of image-guided bronchoscopy, but it is usually combined with image guidance (eg, CT VBN or RP-EBUS) to reach PPLs for biopsy [9,34]. In general, the use of UTB is fairly uncommon since the working channels are small and thus can only accommodate smaller biopsy instruments. (See "Flexible bronchoscopy in adults: Associated diagnostic and therapeutic procedures" and 'Virtual bronchoscopic navigation' above.)
There are no comparative trials of UTB with conventional or other IGB techniques:
●In a meta-analysis that included 39 studies of IGB techniques, 11 used UTB to biopsy PPLs [3]. In almost all of these studies, UTB was combined with other modalities such as VBN or RP-EBUS. Of these, the two studies that utilized UTB alone had diagnostic yields of 60 percent and 70 percent.
●In another trial of 305 patients with PPLs, UTB (3 mm) had a diagnostic yield of 74 percent when used to biopsy PPLs in conjunction with VBN and RP-EBUS, higher than when a standard small bronchoscope (4 mm) was used together with a radial EBUS-guide sheath [37]. Similar diagnostic yields were reported by the same group in a randomized trial that compared the 3 mm UTB with thin 4 mm bronchoscope (70 versus 59 percent); UTB also resulted in a shorter procedure time [38].
CHOOSING A BIOPSY MODALITY
Patient selection — While the optimal approach to managing patients with a PPL is unknown, the general principles of managing a solitary pulmonary nodule (SPN) are typically applied, the details of which are discussed separately. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Management'.)
In general, the following applies:
●Many patients with small or stable PPLs do not need to be biopsied, and CT surveillance is sufficient.
●Surgical biopsy may be preferred in some patients with PPLs who are at high risk of malignancy.
●Nonsurgical biopsy is preferred in those with PPLs who have an intermediate risk for malignancy, those who have a high risk of malignancy who are not surgical candidates, or patients with benign disease amenable to therapy (eg, mycobacterial disease). Image-guided biopsy techniques may be considered as one option among other modalities in this group. (See 'Selection of modality' below.)
Selection of modality — Once the decision is made to biopsy a PPL, a modality needs to be chosen. For patients with PPLs in whom nonsurgical biopsy is indicated, physicians and guidelines vary in their choice, and the decision is frequently individualized depending upon factors including, lesion size, location, presence of emphysema, suspected diagnosis, and institutional expertise [1,12]. Options include transthoracic needle biopsy (TTNB) or bronchoscopic biopsy including conventional and image-guided bronchoscopy (IGB) techniques. Although there is no optimal modality, many experts agree on the following strategy [11,12]:
●CT-guided TTNB may be preferred for PPLs located in proximity to the chest wall or for deeper lesions provided that fissures do not need to be traversed and there is no surrounding emphysema (which increases the risk of pneumothorax). This preference is based upon the higher diagnostic yield associated with TTNB when compared with those reported for IGB techniques. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Transthoracic needle biopsy'.)
●The IGB techniques, electromagnetic navigational bronchoscopy (ENB), radial probe endobronchial ultrasonography (RP-EBUS), robotic bronchoscopy (RB), and combinations thereof are appropriate alternatives to TTNB, particularly in patients who are at high risk of pneumothorax, provided expertise is available. Conventional bronchoscopy may be the only bronchoscopic option available in centers without interventional expertise. (See 'Image-guided bronchoscopy techniques' above.)
●Surgical biopsy is appropriate for those in whom TTNB and/or IGB techniques fail to obtain a diagnosis. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Surgical biopsy'.)
There are no randomized data that report superiority of one procedure over another. One meta-analysis identified 39 studies of bronchoscopy with biopsy guided by RP-EBUS (20 studies), ENB (11 studies), radial EBUS-guide sheath (10 studies), ultrathin bronchoscopy (UTB; 11 studies), or virtual bronchoscopic navigation (VBN; 10 studies) [3]. The overall diagnostic yield was 70 percent (95% CI 67-73), with slightly more favorable results for guide sheath (73 percent), slightly less favorable results for ENB (67 percent), and lower diagnostic yields for small PPLs measuring 2 cm (61 percent).
While IGB techniques have not been directly compared to TTNB, the reported diagnostic yield of IGB techniques is lower than that for TTNB (60 to 70 percent versus >88 percent), but the risk of pneumothorax is also considerably lower (<4 percent versus 10 percent or higher). The diagnostic yield and complications of individual IGB techniques and TTNB are discussed separately. (See 'Image-guided bronchoscopy techniques' above and 'Complications' below and "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Transthoracic needle biopsy'.)
SEDATION — Image-guided bronchoscopy (IGB) procedures are performed either with moderate sedation or with deep sedation/general anesthesia with no comparative data to support the use of one sedation technique over the other. However, many expert operators prefer deep sedation or general anesthesia for virtual or electromagnetic bronchoscopic navigation as these procedures often involve more steps and manipulation and take longer, exceeding normal procedure durations acceptable for moderate sedation. Radial probe endobronchial ultrasound (RP-EBUS) is frequently performed with moderate sedation, but many operators also chose deep sedation/general anesthesia as well. (See 'Virtual bronchoscopic navigation' above and 'Electromagnetic navigation bronchoscopy' above and 'Radial probe endobronchial ultrasound (RP-EBUS)' above.)
A detailed discussion of procedural sedation is provided separately. (See "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications" and "Anesthesia for adult bronchoscopy" and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Preprocedural preparation' and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Sedation' and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Procedural technique'.)
COMPLICATIONS — Image-guided bronchoscopic (IGB) biopsy techniques are generally well tolerated, with reported complication rates ranging from 0 to 8 percent [3,11,13,14,30,39]. IGB techniques typically utilize standard bronchoscopy sampling tools such as forceps, brushes, and needles to biopsy PPLs, and are performed under moderate or deep sedation (see 'Sedation' above). Thus, similar to standard bronchoscopy, the spectrum and rate of complications associated with IGB techniques are procedure related (eg, pneumothorax and bleeding) and/or sedation related (eg, hypotension), the details of which are described separately. (See "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Complications' and "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications", section on 'Anticipating and mitigating Complications'.)
●One large meta-analysis of radial probe endobronchial ultrasonography (RP-EBUS), electromagnetic navigational bronchoscopy (ENB), guide sheath, ultrathin bronchoscopy (UTB), and virtual bronchoscopy (VB) reported an overall adverse event rate of 1.5 percent [3]. Most of these events were pneumothorax with reported ranges across studies of 0 to 7.5 percent and only 0.6 percent requiring a chest tube. One patient experienced respiratory failure and no deaths or major bleeding were described.
●A large review of 1033 ENB procedures reported pneumothoraces in 3.1 percent with only 1.6 percent requiring a chest tube [14]. Significant bleeding occurred in 0.9 percent. When ENB was used in one small study to guide transthoracic needle biopsy, not surprisingly, the pneumothorax rate was higher at 20 percent with 8 percent of subjects requiring a chest tube. A large international prospective cohort study using ENB (NAVIGATE) enrolled 1000 patients and had a pneumothorax rate of 5 percent [40].
●A retrospective series of RP-EBUS in 467 patients resulted in a pneumothorax rate of 2.8 percent and half of those required chest tube drainage [30]. Six patients had bleeding ranging from 100 to 350 mL but required no additional intervention other than suctioning. Another review of RP-EBUS with guide sheath biopsy of peripheral lesions reported lower rates of pneumothorax (0.8 percent) and an infection rate of 0.5 percent [39].
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here is the patient education article that is relevant to this topic. We encourage you to print or e-mail this topic to give to your patient. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Flexible bronchoscopy (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definition and epidemiology – A PPL (also known as peripheral lung lesion [PLL]) is a solitary pulmonary nodule that is located in the lung periphery (table 1). The incidence in the general population is unknown but likely to increase given the widespread use of CT. Several image-guided bronchoscopy (IGB) modalities are available that are capable of obtaining tissue safely from PPLs that are traditionally hard to biopsy using a conventional bronchoscope. (See 'Epidemiology of peripheral pulmonary lesions' above and 'Definition and etiology of peripheral pulmonary lesions' above.)
●Indications and contraindications – IGB techniques are most commonly used to biopsy PPLs. Their use is limited to centers with skilled expertise. Contraindications are similar to conventional bronchoscopy. (See 'Indications' above and 'Contraindications' above.)
●Techniques and efficacy – The diagnostic yield of IGB techniques ranges from 44 to 88 percent, typically varying with lesion size, location, and equipment used as well as other factors including the presence of a bronchus sign and biopsy technique. IGB techniques include the following (see 'Image-guided bronchoscopy techniques' above):
•Virtual bronchoscopy (VB) – VB is a noninvasive form of bronchoscopy that reconstructs the airways in a three-dimensional manner, producing images that appear similar to those visualized during invasive bronchoscopy. VB cannot biopsy lesions per se but can be used to navigate (VBN) conventional bronchoscopes and other biopsy equipment to the target PPLs. (See 'Virtual bronchoscopy' above and 'Virtual bronchoscopic navigation' above.)
•Electromagnetic navigation bronchoscopy (ENB) – ENB is the most common IGB technique. It incorporates VB imaging with an electromagnetic field, an additional navigational tool, to guide biopsy equipment (eg, forceps, brush, guide sheath) to the target lesion. ENB can be used alone or in combination with radial probe endobronchial ultrasonography (RP-EBUS) to biopsy PPLs. (See 'Electromagnetic navigation bronchoscopy' above.)
•Robotic bronchoscopy (RB) – RB is a rapidly evolving technique that utilizes navigational techniques as well as robotic bronchoscopes that can be driven to peripheral lesions. Standard biopsy instruments are used through the RB to obtain specimens. One system allows for a real-time camera view at the tip of the instrument during biopsy. (See 'Robotic bronchoscopy' above.)
•RP-EBUS – RP-EBUS is an adjunctive imaging tool used to visualize the target lesion prior to biopsy. It can be used together with conventional bronchoscopy as well as with navigational tools (virtual or electromagnetic), to facilitate biopsy of PPLs. Neither RP-EBUS nor ENB provide actual real-time biopsy visualization as the ultrasound or navigation probes must be removed in order to pass the biopsy instruments. (See 'Radial probe endobronchial ultrasound (RP-EBUS)' above.)
•Other techniques, including CT bronchoscopy and ultrathin bronchoscopy (UTB) are rarely used and their role remains largely investigational. (See 'Other' above.)
●Choosing a biopsy modality – For patients with PPLs in whom nonsurgical biopsy is indicated (eg, PPLs of intermediate risk of malignancy), when expertise is available, IGB techniques are appropriate alternatives to transthoracic needle biopsy, particularly in patients who are at high risk of pneumothorax. Choosing among the options is individualized and depends upon factors including lesion size, location, presence of emphysema, suspected diagnosis, and institutional expertise. (See 'Choosing a biopsy modality' above and "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Management'.)
●Sedation – IGB procedures can be performed with moderate sedation. However, deep sedation/general anesthesia is often required, particularly when complex and lengthy procedures are expected. (See 'Sedation' above and "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications".)
●Complications – IGB techniques are generally well tolerated with reported complication rates ranging from 0 to 8 percent. Similar to standard bronchoscopy, the spectrum and rate of complications are procedure related (eg, pneumothorax and bleeding) and/or sedation related (eg, hypotension). (See 'Complications' above and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Complications'.)
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