Transbronchial Biopsy 

Updated: Apr 16, 2019
Author: Klaus-Dieter Lessnau, MD, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP 

Overview

Background

Transbronchial biopsy is performed by pulmonologists to diagnose focal and diffuse lung diseases. Compared with open lung biopsy, transbronchial biopsy has lower morbidity and mortality. Biopsy of the lung was performed by means of open surgical methods until 1963, when Anderson performed bronchoscopic lung biopsy with a rigid bronchoscope. In 1974, Levin et al published their experience with transbronchial biopsy using flexible bronchoscopy. This approach has two main rare complications: pneumothorax and severe pulmonary bleeding.

Advances in technology are leading to improved yields with fewer complications. Endobronchial ultrasonography (EBUS)-guided needle aspiration can be used for mediastinal lymph nodes if these are present and can replace transbronchial biopsy, especially for suspected sarcoidosis. Cryobiopsy of the lung provides a larger specimen without crush artefacts and may replace open lung biopsy.

Current technology includes three-dimensional (3D) preprocedural computed tomography (CT) planning, radial ultrasonography (with a small fiber), and possibly navigational bronchoscopy. Dual bronchoscopy, with one bronchoscope for cryobiopsy and a second with a balloon-tip catheter, will avoid pneumothorax and massive bleeding.[1, 2]

Indications

Transbronchial biopsy is employed in the settings of neoplastic disease, suspected sarcoidosis or hypersensitivity pneumonitis, interstitial lung disease,[3] pulmonary infection, unusual and unclear lung disease, and lung transplantation.

Transbronchial biopsy is commonly used to determine the etiology of lung nodules and masses. Its diagnostic accuracy increases when the nodule is larger than 2 cm, when the presence of a bronchus leading to the nodule is found on CT of the chest (positive bronchus sign), and when the tissue is repeatedly sampled. The yield of transbronchial biopsy is also high in bronchoalveolar carcinoma and lymphangitic spread of the tumor.

The diagnostic yield of this procedure can be significantly increased (to 73%) by combining flexible bronchoscopy with CT guidance in a dedicated low-dose protocol.[4]  In another study, the sensitivity of transbronchial biopsy for a solitary pulmonary nodule was 62.2% with multislice CT guidance, compared with 52.6% with fluoroscopic guidance.[5]  However, this technique is not cost-effective and has not been frequently used.

Transbronchial biopsy may not be reliable for heterogeneous lung diseases such as usual interstitial pneumonia.[6, 7]  However, it has a high diagnostic yield for sarcoidosis: Sensitivity ranges from 50% to 85% in stage 1 disease and is higher if the parenchyma is involved. At least four to six biopsies are required for optimal diagnosis of sarcoidosis.[8]  Transbronchial biopsy is also highly sensitive in diagnosing pulmonary alveolar proteinosis, Langerhans cell histiocytosis, eosinophilic pneumonia, lipoid pneumonia, drug-induced pneumonitis, and miscellaneous lung disease.

Transbronchial biopsy is indicated in the diagnosis of pulmonary infections in the immunocompromised patient. Although most pulmonary infections can be diagnosed by performing a bronchoalveolar lavage, transbronchial biopsy increases the diagnostic yield and rules out noninfectious causes. In particular, transbronchial biopsy increases the diagnostic yield for Pneumocystis jiroveci (carinii) pneumonia in patients with cancer, bone marrow transplant recipients, and those receiving immunosuppressive drugs.[9, 10]

Transbronchial biopsy is used in the diagnosis of allograft rejection in lung transplantation.

EBUS-guided needle aspiration is increasingly used to diagnose sarcoidosis. Cryobiopsy is used for interstitial lung disease (eg, suspected pulmonary fibrosis). A retrospective analysis by Ussavarungsi et al found transbronchial cryobiopsy to have a 51% diagnostic yield in the setting of diffuse parenchymal lung disease.[11]

Contraindications

Absolute contraindications for transbronchial biopsy include medical instability, severe hypoxia, status asthmaticus, lack of patient cooperation, malignant arrhythmia, massive hemoptysis, and uncorrectable bleeding diathesis.

Relative contraindications include the following:

  • Thrombocytopenia - Use caution when the platelet count is less than 50,000/μL
  • Uremia - A danger of serious hemorrhage exists, even in the presence of normal coagulation parameters; biopsies may be done carefully, preferably soon after dialysis or administration of desmopressin (DDAVP) and cryoprecipitate
  • Mechanical ventilation - The benefits of transbronchial biopsy should be weighed against the risk of developing tension pneumothorax
  • Pulmonary hypertension - Recommendations from the British Thoracic Society (BTS) suggest that transbronchial biopsy should be performed with caution in patients with elevated pulmonary arterial pressures
  • Risk of arrhythmia - The BTS recommends oxygen supplementation to keep the blood oxygen saturation above 90% and thereby minimize the risk of cardiac arrhythmia during and after bronchoscopy
  • Certain drugs - Aspirin can be continued if indicated, but clopidogrel is discontinued at least 5 days before the procedure; the BTS recommends discontinuing warfarin 3 days before the procedure and suggests that an international normalized ratio (INR) lower than 1.5 is safe; heparin is discontinued 6 hours before the procedure; therapeutically dosed enoxaparin is discontinued 24 hours beforehand, whereas enoxaparin given for prophylaxis of deep vein thrombosis prophylaxis is discontinued on the morning of the procedure

Technical Considerations

Certain technical considerations may improve the diagnostic performance of transbronchial biopsy and reduce the incidence of complications. Twisting the forceps as opposed to pulling may decrease bleeding (unpublished expert opinion). Not suctioning after bleeding will stop bleeding faster.

Best practices

The number of biopsy specimens required for optimal diagnostic yield has been reported to be four to 10.[12]  The 2013 BTS guidelines recommend that at least five samples should be obtained in cases where endobronchial tumor is visible and that at least five or six samples should be obtained in cases of interstitial lung disease; fluoroscopy should be employed with transbronchial biopsy in cases of localized or focal parenchymal lung disease.[13]

Transbronchial biopsy with fluoroscopy has not been associated with a significantly lower incidence of pneumothorax than biopsy performed without fluoroscopy.[14]  The use of fluoroscopy during transbronchial biopsy has been shown to increase the diagnostic yield in focal lesions,[15]  though it has not been found to provide a comparable benefit in diffuse lung diseases such as sarcoidosis.[16]

A comparison of transbronchial biopsy specimen yield between the use of standard-sized forceps and the use of large forceps found no significant differences in the size of the biopsies or in the amount of alveolar tissue collected.[17]  The use of large forceps does prevent effective suctioning of secretions. In 2008, Casoni et al reported that the use of large biopsy forceps to perform transbronchial biopsy via a rigid bronchoscope significantly increased the diagnostic yield in diffuse infiltrative lung disease.[18]

The tissue samples obtained by means of transbronchial biopsy forceps are small (~3 mm). Therefore, this procedure is less useful in diagnosing heterogeneous lung diseases such as idiopathic interstitial fibrosis.

Combining suction catheter aspiration with forceps biopsy for bronchoscopic tissue sampling results in a higher diagnostic yield than use of either method by itself.[19]

Complication prevention

Optimal sedation, adequate topical anesthesia, and proper technique all reduce the incidence of complications related to the procedure (see Periprocedural Care and Technique). The use of fluoroscopy equipment before the procedure may increase the diagnostic yield and provide a statistically insignificant decrease in pneumothoraces. The presence of an additional pulmonologist, intensivist, or anesthesiologist for sedation is likely to decrease complications. Appropriate expertise for managing pneumothorax and massive bleed must be available for rare emergencies, including balloon catheters and chest tubes.

 

Periprocedural Care

Preprocedural Planning

Occasionally, the patient is premedicated with atropine, glycopyrrolate, or scopolamine in an effort to reduce secretions. These medications are almost outdated.

Computed tomography (CT) of the chest is usually performed before bronchoscopy and is useful in predicting the yield of transbronchial biopsy on the basis of the anatomic distribution and appearance of any abnormalities. CT sometimes enables a specific diagnosis in the appropriate clinical context, particularly in patients with sarcoidosis, usual interstitial pneumonia, subacute hypersensitivity pneumonitis, acute eosinophilic pneumonia, Langerhans cell histiocytosis, or lymphangioleiomyomatosis. CT images should be reviewed by the bronchoscopist before the procedure; radiology reports alone cannot be relied upon.

Even when CT scans are nonspecific, peribronchovascular and central abnormalities are much more amenable to specific diagnosis by transbronchial biopsy than peripheral or nonsegmental disease is. Transbronchial biopsy is often diagnostic in patients in whom the CT findings are those of centrilobular nodules of ground-glass attenuation.[20]

Equipment

Transbronchial lung biopsy must be performed in a well-equipped room with facilities for monitoring blood pressure, oxygen saturation, heart rate, respiratory rate, and possibly end-tidal CO2. An adult-sized flexible bronchoscope, a light source, video monitoring equipment, a biopsy forceps (see the image below), specimen containers, equipment for cardiopulmonary resuscitation, a suction apparatus, and supplemental oxygen are necessary for performing transbronchial biopsy. Most important, a bag-valve mask must be easily available.

Transbronchial biopsy forceps. Transbronchial biopsy forceps.

There are three common types of biopsy forceps that may be used for the procedure, as follows:

  • Cup forceps
  • Toothed forceps
  • Forceps with an impaler needle

Biplane fluoroscopy equipment is necessary for accurate localization of the lesion (see the image below). These machines may be portable or fixed.

Fluoroscopic image of transbronchial biopsy forcep Fluoroscopic image of transbronchial biopsy forceps.

Patient Preparation

Transbronchial biopsy is usually performed with the patient in the supine position. Typically, topical anesthesia with lidocaine (2-4%) is applied directly to the nasal mucosa with an atomizer; alternatively, cotton-tipped applicators saturated with lidocaine can be applied to the nose. Lidocaine spray is used to anesthetize the oropharynx. Laryngeal anesthesia is accomplished by aerosolizing lidocaine with an ultrasonic nebulizer system.

The procedure is then carried out with the patient under conscious sedation induced by intravenous (IV) narcotics and benzodiazepines. Incremental dosing of sedatives is safe and facilitates the performance of transbronchial biopsy. Careful monitoring is required because both benzodiazepines and narcotics cause varying degrees of respiratory depression. General anesthesia may be required if rigid bronchoscopy is performed.

Midazolam is the benzodiazepine of choice for short-term sedation because it has the highest lipid solubility, the fastest onset of action (1-5 minutes), and the shortest duration of action (1-2 hours) of all the IV benzodiazepines. The loading dose is 0.02-0.1 mg/kg.

Fentanyl is the narcotic most frequently used for conscious sedation. It is 600 times more lipid-soluble than morphine and thus is more readily taken up into the central nervous system. Fentanyl causes fewer hemodynamic effects than morphine, has a quicker onset of action (1-2 minutes), and provides equivalent analgesia at a fraction (1/100) of the dose of morphine. The loading dose is 50-100 µg, and the duration of action is 30-60 minutes.

Propofol and dexmedetomidine are increasingly used.

 

Technique

Transbronchial Biopsy

Flexible bronchoscopy is performed via the transnasal or transoral approach after appropriate topical anesthesia and conscious sedation. Fluoroscopy is commonly used as an adjunct to the procedure.

A complete endobronchial inspection of all segments of both lungs is carried out to exclude significant endobronchial abnormalities. The flexible bronchoscope is wedged in the segmental bronchus of interest, and the biopsy forceps is passed through the working channel of the bronchoscope.

As the biopsy forceps is seen to enter the pulmonary subsegment, the fluoroscopy unit is activated to allow visualization of the forceps as it enters the distal segments of the lung. The biopsy forceps is advanced to the periphery of the diseased region until resistance is encountered. Placement of the biopsy forceps near, but not at, the lung surface minimizes the risk of pneumothorax.

Next, the forceps is withdrawn approximately 1 cm, and the jaws are opened and advanced slightly to obtain the sample of the lung. The forceps is then advanced close to the area where resistance was encountered, and the jaws are closed. If the patient experiences pain at this point, the forceps is opened and withdrawn; the only pain-sensitive structure in the area is the visceral pleura.

The biopsy forceps is firmly retracted to obtain the sample, with a careful eye to resistance or excessive retraction. Twisting the forceps may be better than pulling the forceps, in order to decrease tissue shearing. The sample is placed in formalin and sent for histopathologic evaluation.

The ideal transbronchial biopsy specimen consists of four to six samples, with at least one sample containing full-thickness bronchial mucosa and some alveolar parenchyma.

Newer guidance approaches

Navigational bronchoscopy (or electromagnetic navigation bronchoscopy [ENB]) is a procedure involving a specialized chest computed tomography (CT) scan that is used with a magnetic field and computer software to guide the transbronchial forceps to the peripheral area of interest.[21]  It is employed for small peripheral lesions, especially in the upper lungs.

ENB is not as accurate in lower-lung lesions, because the CT scan is obtained in end-inspiration and the bronchoscopy is performed during tidal breathing. Therefore, the CT scan should be obtained at tidal volume breathing. Unfortunately, it is not real-time imaging because the scan was obtained days if not weeks earlier. Technical advances are expected eventually to increase diagnostic yield, thus avoiding transthoracic needle aspiration (with its pneumothorax risk) and more invasive video-assisted thoracoscopic surgery (VATS) in the operating room.[22]

Endobronchial ultrasonography (EBUS) with a small catheter probe or a radial balloon catheter can also be used to help guide the practitioner to the peripheral lesion. After ultrasound imaging, the catheter must be removed and the forceps introduced through the working channel. It is important that the patient does not cough while the ultrasound probe is being changed to the forceps, so as to avoid dislodging of the flexible bronchoscope.[23, 24, 25]  The imaging EBUS devices deliver increasingly better resolution.

Techniques for guidance to small peripheral nodules are emerging rapidly. Virtual three-dimensional (3D) CT can be used prior to the procedure to guide the pathway. The bronchus sign (a bronchus leading into the lesion) is useful. Confocal laser endomicroscopy for real-time "optical biopsy"  is developing.

Electromagnetic Navigational Bronchoscopy

ENB (also sometimes referred to as Navi) is a minimally invasive approach to guide bronchoscopic biopsies or needle aspiration to small pulmonary nodules. ENB is particularly useful in the setting of lung nodules; the detection of early lung cancer is important to allow early successful treatment. Conversely, late detection of lung cancer has usually a bad outcome.

Before the development of ENB, when a patient presented with a lung lesion, there were three ways to obtain a biopsy, as follows[26] :

  • Bronchoscopic lung biopsy
  • Transthoracic needle aspiration (TTNA)
  • Surgical resection

Each of these methods presents with logistic disadvantages, particularly if a lesion is out of the reach of a regular bronchoscope, if the patient cannot tolerate potential complications (eg, pneumothorax) because of poor baseline lung function, or if the patient is not a surgical candidate.

In ENB, a computer system with proprietary software converts images from a patient's CT scan to construct a 3D road map for the "navigational" purpose of guiding bronchoscopy, particularly in the endobronchial tree. The planning data using such software could be performed even while the patient is undergoing preprocedural anesthesia and additional preparation.

The planning data are uploaded into an electromagnetic navigation board, where they can be viewed by the operator.[26]  The operator then uses a steerable sensor probe that is guided to the lesion, and a small sheath is left in place as a residual extended working channel. With such tools in place, there can be guided advancement of needles, forceps, and brushes into small pulmonary nodules.

The efficacy of ENB as a diagnostic tool has been extensively studied. ENB has been shown to achieve a diagnostic yield of 67-74% with complication (pneumothorax) rates of 2.2-3.5%, depending on the study.[27, 28, 29]  ENB can also serve to place fiducial markers, which are useful for guidance of stereotactic radiotherapy or VATS. In one study of 64 patients, the retention rate of fiduciary markers for ENB was as high as 82% overall: 78% for upper-lobe lesions and 89% for middle-/lower-lobe lesions.[30]

Given the rate of success of ENB in its applications, it is possible to avoid nontherapeutic thoracic surgery of benign nodules, for which rates have been reported to be anywhere in the range of 20-49% of patients with lung lesions who underwent surgical resection.[26]

One disadvantages is that ENB is a very expensive procedure. The equipment is quite costly, and all the catheters, including the probe, the needles, the triple needle brushes, the biopy forceps, and other tools can be used only once, which adds to the costs. The yield is not much higher than with conventional methods. Many experts have pointed out that conventional techniques (eg, radial ultrasonography, fluoroscopy, and virtual bronchoscopy with a 3D CT image) have similar yield, as long as several tools (eg, needle, forceps, and brush and washings) are used. This issue remains controversial.

Furthermore, the CT image used is not real-time and is usually inspiratory only. Nodule location changes with respiration during bronchoscopy and is not captured with an end-inspiratory CT. Quite often, the CT scan obtained cannot be used, and an additional dedicated scan must be obtained, which adds to the patient's exposure. Navigational bronchoscopy may not be ready to outsource percutanous needle biopsy with the radiologist and real-time CT observation.

Postprocedural Care

After the procedure, it is important to monitor the patient at least for 1 hour. Heart rate, blood pressure, respiratory rate, and oxygen saturation should be recorded. If the patient is asymptomatic, he or she can be discharged.

Patients receive appropriate monitoring in accordance with the prevailing policy and procedures for moderate sedation and analgesia.

If there is any discomfort, such as shortness of breath or chest pain, chest radiography should be performed to evaluate for possible pneumothorax before the patient leaves the facility. However, studies have shown that routine chest radiography after transbronchial biopsy is not cost-effective in asymptomatic patients.[31]

Instructing the patient to remain NPO (no eating or drinking) for another 3 hours is probably useful.

Administration of anticoagulants and antiplatelet agents can be resumed 12-24 hours after the procedure.

Complications

The major complications of transbronchial biopsy are pneumothorax and bleeding.

Pneumothorax occurs in 1-6% of patients undergoing transbronchial biopsy. A prospective study of 350 cases showed that chest radiographs are not routinely necessary after the procedure[31]  and that the size of the pneumothorax was correlated with the symptoms. Pneumothorax is rare but may require a pigtail catheter for reexpansion.

With minor bleeding, watchful waiting with the bronchoscope is usually successful. Avoid suctioning close to the area of the biopsy so as not to suck away the blood clot. This type of bleeding is usually self-limited.

Massive pulmonary bleeding could develop into a catastrophe. Significant bleeding is observed in 2-9% of patients. The risk of bleeding is the main limiting factor in obtaining more or larger biopsy samples. One of the techniques commonly used to control procedural bleeding is the wedge technique, first described by Zavala in 1976.[32]  In this technique, the bronchoscope is wedged into the appropriate segmental bronchus, and blood is continuously suctioned to avoid contamination.

Another strategy involves removing the bronchoscope from the segment of interest and suctioning blood to maintain a patent airway. Other options for controlling bleeding include administration of iced saline, instillation of 20 mL of 1:20,000 epinephrine, positioning the patient with the bleeding lung down, and, finally, placement of an endobronchial blocker.

The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser and, especially, argon plasma coagulation (eg, 27 J, 0.5 flow) are useful for stopping bleeding.

Positioning of the bleeding lung down, with single-lumen intubation and a bronchial balloon blocker, can be very helpful. Avoid double-lumen intubation; it is difficult to insert during an emergency, and the lumina often are too small for effective suctioning.

Rare complications that have been reported include mediastinal and subcutaneous emphysema.