Transbronchial cryobiopsy (TBCB) is a relatively new technique in the diagnosis of diffuse parenchymal lung disease (DPLD). The basic rationale for development of TBCB is based on the inferiority of standard forceps transbronchial biopsies (TBBx) for diagnosis of DLPD as compared to surgical lung biopsies (SLBs). This is due to the small specimen sizes and resultant sampling error with TBBx. As a result, it is recommended that TBBx not be performed in the diagnostic evaluation of usual interstitial pneumonia (UIP), the pathologic correlate to idiopathic pulmonary fibrosis (IPF). In addition, it has been increasingly recognized that SLB carries a risk of morbidity and mortality that may be unacceptable to both clinicians and patients. TBCB was developed with three objectives in mind: (1) obtain large enough tissues samples that would be representative of the underlying disease process and positively influence the diagnostic decision-making of a multidisciplinary discussion (MDD), (2) provide diagnostic accuracy approaching that of SLB, and (3) carry less complications than SLB.
The procedure has grown in popularity, with recent data suggesting a good correlation with SLB. It has recently been recommended as a suggested diagnostic test in the evaluation of fibrotic hypersensitivity pneumonitis.
TBCB is a procedure performed via either flexible or rigid bronchoscopy under general anesthesia in which a flexible cryoprobe is advanced to preplanned diseased locations within the lung based on the high-resolution computed tomography (HRCT) scan. The cryoprobe is then frozen for 3–5 s (sometimes longer depending on the time taken to generate a 5-mm ice ball at the tip of the cryoprobe) and adherent tissue is extracted en bloc with the cryoprobe. This method has allowed for consistently larger and more intact samples without crush artifact than traditional TBBx forceps ( Fig. 5.1 ).
Guidelines have been recently developed to facilitate standardization of TBCB to ensure patient safety and optimize diagnostic yield.
General principles for performing TBCB consist of (1) appropriate training in the technique, (2) appropriate patient selection, (3) general anesthesia with either an endotracheal tube (ETT) or rigid bronchoscopy, (4) a prophylactic balloon blocker placement, and (5) fluoroscopic guidance.
The importance of proper training in the technique, either within a dedicated interventional pulmonology fellowship or with mentoring over several procedures by an experienced bronchoscopist, cannot be overemphasized. In order to safely perform this procedure and maintain a complication rate that is comparable to that reported in the peer-reviewed literature, bronchoscopy teams should have expertise in the management of life-threatening airway hemorrhage and tension pneumothorax. Familiarity with balloon bronchial blockers is mandatory, as well as expertise with rigid bronchoscopy.
While no specific criteria exist for patient selection in evaluating someone for TBCB, in general, patient selection should mirror that followed for SLB. Developing a simple preprocedure evaluation checklist will help ensure proper patient selection and patient safety ( Table 5.1 ):
Clinical stability: A general rule of thumb is that if a patient is unsuitable for SLB, then they are probably unsuitable for TBCB. If the patient has clinical signs or symptoms consistent with worsening DPLD, particularly if an acute exacerbation of IPF is suspected, then the procedure should be canceled. Worsening dyspnea, progressive or rapid decline in diffusing capacity for carbon monoxide (D lco ), or signs of progressive groundglass opacities are all suggestive of worsening disease process. While TBCB has been performed in patients on mechanical ventilation, we suggest that in the absence of data demonstrating improved patient outcomes, this should not be considered.
Medications: Anticoagulants, clopidogrel, ticagrelor, other antiplatelet drugs, aspirin, and herbal supplements that increase bleeding should be stopped.
Laboratory data: International normalized ratio (INR) should be <1.5 and platelet count >50,000. No specific cut-off value for creatinine and blood urea nitrogen has been established, but it is prudent to avoid TBCB in patients with end-stage renal disease (ESRD) on dialysis until more data are available.
Pulmonary function tests: D lco should be >35%, forced vital capacity (FVC) > 50%, and total lung capacity (TLC) > 50% predicated. A D lco of <35% increases the probability of adverse outcomes and mortality at 30 and 90 days.
Hypoxia: Pa o 2 > 55–60 or an Sp o 2 > 90% while on 2 L of oxygen via nasal cannula is considered a requirement by some, while others consider any use of supplement oxygen a contraindication. Intraprocedural techniques to assess the patient’s ability to safely tolerate transient peribiopsy hypoxia are detailed later.
Obesity: There should be no significant abdominal obesity. A BMI <35–40 kg/m 2 is considered by some to be a reasonable cut-off value. Significant abdominal obesity may make it difficult to complete the procedure due to the rapid development of atelectasis and increased risk of periprocedural hypoxemia.
Pulmonary hypertension: A transthoracic echocardiogram is usually sufficient and is recommended to obtain before the procedure as many patients with DPLD may have coexistent pulmonary arterial hypertension. Pulmonary artery systolic pressure less than 50 mmHg with normal right ventricular function is recommended. Some centers use BNP as a surrogate marker to exclude significant pulmonary hypertension.
Comorbid medical conditions: Uncontrolled hypertension, congestive heart failure, ischemic heart disease, ESRD on dialysis, severe aortic stenosis, significant centrilobular emphysema or bullous lung disease in the area of biopsy, and thromboembolic disease unable to stop anticoagulation or with significant right heart dysfunction are considered contraindications to TBCB.
|Clinical stability (outpatient status and not hospitalized or with signs/symptoms consistent with worsening of lung disease)|
|Anticoagulant and antiplatelet therapy|
|BMI <35 kg/m 2|
|Pulmonary hypertension (PASP <50 mmHg by echocardiogram)|
1.9 mm or 2.4 ERBE cryoprobe (ERBE, Marietta, GA, USA)
ERBE cryo machine with CO 2 or N 2 O gas
Flexible bronchoscope with minimum 2.8-mm working channel for 2.4-mm probe (larger working channel recommended for greater suction capacity if not using rigid bronchoscopy)
Rigid bronchoscope (operator dependent)
Rigid suction catheter (operator dependent)
Bronchial blocker (Arndt or Fogarty balloon; Arndt 7 or 9 French; the balloon should be large enough that, when inflated, it obstructs the segmental or mainstem bronchi proximal to the site of the biopsy)
Endotracheal tube (standard or wire-reinforced)
C-arm fluoroscopy machine
Basin with normal saline
Formalin specimen collection containers
Iced saline or other vasoconstrictor agent
Second bronchoscopist or trained bronchoscopy technician to assist with prophylactic balloon inflation
Bronchoscopy technician to assist with specimen collection
Bronchoscopy nurse to administer sedative medications and monitor the patient, if required
Location suitable for general anesthesia (bronchoscopy suite or operator room).
Flexible Bronchoscopy Approach
Anesthesia, ventilation, and airway
General anesthesia, with or without neuromuscular blockade with placement of an ETT, provides a secure airway in the event of massive airway hemorrhage. By eliminating the cough reflex, risk of malposition of the cryoprobe during the procedure with the unintended consequence of moving the probe either too far into the periphery or too proximal in the chest is reduced. Positive end-expiratory pressure should be kept at a minimum (maximum 5 cmH 2 O).
One of the benefits of using an ETT is the appropriate placement of an endobronchial balloon blocker. There are two methods for placement of the endobronchial blocker in relation to the ETT: (1) within the ETT or (2) external to the ETT. If the endobronchial blocker is passed within the ETT, the patient is first intubated in the standard manner. An Arndt endobronchial blocker is passed through the ETT connector and secured to the tip of the flexible bronchoscope. The connector with the endobronchial blocker attached to the bronchoscope is then attached to the ETT and the balloon blocker is guided through the ETT and positioned proximal to the airway segments being biopsied ( Figs. 5.2 and 5.3 ). One potential limitation to this approach is that the balloon may cause partial obstruction of the ETT and impair removal of the bronchoscope and cryoprobe following biopsy, raising the risk of balloon dislodgement. Alternatively, the endobronchial blocker may be external to the ETT. With this method, the patient is fiberoptically intubated (either awake fiberoptic intubation, followed by total intravenous anesthesia [TIVA] once the tube has been secured or fiberoptic intubation following induction with anesthesia) with an Arndt endobronchial blocker positioned “piggyback” alongside the ETT ( Fig. 5.4 ). This allows ease of placement of the balloon blocker at time of anesthesia induction without obstructing the ETT ( Fig. 5.5 ). One potential advantage of the ETT with an external blocker technique is the ability to selectively intubate the contralateral lung in the setting of severe hemorrhage while leaving the balloon in place on the bleeding side. If the balloon is placed in the lumen of the ETT, the balloon would have to be deflated and retracted in order to pass the ETT into the contralateral mainstem bronchi. A flexible spiral, wire-reinforced ETT ( Fig. 5.6 ) is useful in these circumstances and facilitates easy insertion into the more angulated left mainstem bronchus if biopsies are taken in the right lung and massive bleeding is encountered.