Usefulness and safety of transbronchial biopsy with large forceps during flexible bronchoscopy

Abstract

Transbronchial lung biopsy (TBLB) using forceps is one of the most common procedures used to obtain lung tissue. The procedure’s usefulness remains limited when diagnosing interstitial lung diseases. This retrospective descriptive study analyzed the feasibility and safety of using large forceps for TBLB in all patients who underwent TBLB from 2014 to 2018 for diffuse lung disease where the diagnosis could not be made by high-resolution chest computed tomography. We excluded patients with radiographic features of usual interstitial pneumonia. Among the 35 study patients, 7 were men and 28 were women. Diagnoses included respiratory associated bronchiolitis (7), diffuse alveolar damage (4), organizing pneumonia (4), nonspecific interstitial pneumonitis (3), acute fibrinous organizing pneumonia (3), sarcoidosis (2), hypersensitivity pneumonitis (2), IgG4 interstitial lung disease (1), eosinophilic pneumonia (1), pulmonary alveolar proteinosis (1), pulmonary fibrosis (1), pneumocystis (1), plasma-rich bronchiolitis (1), and diffuse alveolar hemorrhage (1). In three cases, the biopsies were nondiagnostic. Two patients developed a pneumothorax, and one required chest tube placement. There was one episode of minor bleeding. No escalation of care or hospitalization was required. Large-forceps TBLB is a feasible and safe method for obtaining parenchymal lung biopsies.

Transbronchial lung biopsy (TBLB) is one of the most common procedures used to obtain lung tissue samples during flexible bronchoscopy.^1–4 Despite its proven utility in the diagnosis of several types of lung pathology, including malignancy, sarcoidosis, infectious processes, posttransplant rejection, and certain interstitial lung diseases, its usefulness remains very limited for the diagnosis of idiopathic pulmonary fibrosis and for distinguishing between different subtypes of idiopathic interstitial pneumonias.^1,3,5 This is primarily related to the small sample size obtained. No specific guidelines or recommendations indicate the type or size of forceps that should be used. The choice is usually determined by user preference or limited by the working channel of the bronchoscope. Most operators are comfortable with regular biopsy forceps (standard oval 5 mm cup opening and 2.0 mm required channel), which usually leads to a small sample size. Recently, transbronchial cryobiopsies (cTBLB) have emerged as a potential alternative to surgical lung biopsy for the diagnosis of interstitial lung disease, although the method has not been widely accepted due to lack of high-quality evidence supporting its accuracy and rising safety concerns.⁶ The technique for cTBLB varies significantly among interventional pulmonologists, raising concerns about safety and competency.⁷ In our practice, we routinely use large forceps to perform TBLB. In this retrospective descriptive study, we report the utility and safety profile for use of large forceps in TBLB.

METHODS

We conducted a retrospective chart review of patients who underwent large-forceps TBLB at Cooper University Hospital between January 2014 and January 2018. All subjects (or their parents or guardians) provided written informed consent, and the study protocol was approved by the Cooper Health System institutional review board. We included all patients who underwent large-forceps TBLB for diffuse lung disease whose diagnosis could not be made by high-resolution CT alone. Patients with radiographic patterns consistent with definite usual interstitial pneumonia on CT chest were excluded. This diagnosis was made by the radiologist. Data collected included age; gender; CT scan pattern; number, location, and size of sample obtained; final diagnosis; and complications.

An Olympus therapeutic bronchoscope with a 2.8 mm working channel was used for the procedure with a reusable large biopsy forceps (Boston Scientific Radial Jaw M00515200, 7.3 mm cup opening size and 2.8 mm required scope channel) (Figure 1). All biopsies were performed with fluoroscopic guidance and targeted the lateral segments to ensure it was easy to determine the forceps position in relation to the pleural lines. Prior to biopsy, the areas were prepped with 60 cm³ cold saline aliquots and 5 cm³ lidocaine/epinephrine 1%. Forceps were advanced under direct and fluoroscopic guidance until reaching the pleural line, at which time they were pulled back 3 cm, opened, and then advanced until approximately 2 cm from the pleural line. After the biopsies were taken, the bronchoscope remained wedged in the airway, and suction was immediately activated to collapse the targeted airway and achieve hemostasis. Three to five biopsies were obtained from a single targeted lobe. Bleeding severity was scored based on previous papers (Table 1).

Figure 1.

Large forceps vs standard forceps.

Table 1.

Bleeding score

Score	Description
0	No bleeding or only traces of blood not requiring suction
1	Bleeding requiring suction to clear
2	Bleeding requiring wedging of the biopsied segment with the flexible bronchoscope and/or iced saline
3	Bleeding requiring inflation of a bronchial blocker
4	Bleeding causing cardiopulmonary instability

RESULTS

A total of 35 patients were included in the analysis. Patient characteristics and complications are listed in Table 2. The most common diagnoses were respiratory-associated bronchiolitis, diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonitis, and acute fibrinous and organizing pneumonia (Table 3, Figure 2).

Table 2.

Characteristics of 35 patients undergoing transbronchial lung biopsy

Variable	N
Male	7
Female	28
Mean age (years)	56
Smoker	19
Pneumothorax	2
Pneumothorax requiring chest tube	1
Bleeding	1

Table 3.

Characteristics of biopsy specimen and pathological diagnosis of 35 patients undergoing transbronchial lung biopsy

Pathological diagnosis	N	Biopsy size (mm)a
Respiratory bronchiolitis – ILD	7	1–4	2.5
Diffuse alveolar damage	4	2–6	4
Organizing pneumonia	4	1–6	3.5
Nonspecific interstitial pneumonia	3	1–4	2.5
Acute fibrinous organizing pneumonia	3	1–5	3
Nondiagnostic	3	1–4	2.5
Sarcoidosis	2	1–10	5.5
Hypersensitivity pneumonitis	2	1–2	1.5
IgG4 ILD	1	4	4
Eosinophilic pneumonia	1	6	6
Plasma-rich bronchiolitis	1	2	2
Diffuse alveolar hemorrhage	1	5	5
Pulmonary alveolar proteinosis	1	3–5	4
Pulmonary fibrosis	1	1	1
Pneumocystis pneumonia	1	5	5

ILD, interstitial lung disease.

^aOverall average = 3.7 mm.

Figure 2.

(a) Acute lung injury pattern, consistent with diffuse alveolar damage, exudative and proliferative phases (low power). (b) Acute lung injury pattern showing diffusely thickened alveolar septa with type II pneumocyte hyperplasia and organizing fibrin exudates lining alveolar walls. (c) Organizing pneumonia with fibroblast plugs filling alveolar spaces and associated mild interstitial chronic inflammation. (d) Alveolar spaces filled with eosinophilic proteinaceous granular exudate. (e) Intraalveolar exudate staining positive on PAS stain. (f) Confirmatory surfactant immunohistochemical stain.

Two of the 35 patients developed a pneumothorax but only one required chest tube placement for 24 hours. One patient had grade 2 bleeding, which was controlled by wedging the bronchoscope in the targeted segment, instilling ice-cold saline, and applying intermittent suction. The patient did not require blood transfusion. None of the complications required escalation of care. No iatrogenic injuries to the bronchoscope channel were reported.

DISCUSSION

TBLB was first performed in the 1960s. During these procedures, flexible forceps were used through a rigid bronchoscope to obtain lung biopsies. Anderson et al showed that this approach could obtain lung tissue safely.⁸ Among 450 procedures, the pneumothorax rate was 11% with one death.^8,9 With the introduction of the flexible bronchoscope, TBLB was more widely performed and considered a less invasive and safer method of tissue acquisition.^10,11 The complication rates from TBLB remain consistently low, with pneumothorax being the most common. Pneumothorax rates have ranged from 0% to 12%,^{1–4,12–16} while the rate of significant bleeding has been 0% to 20%.^{1,3,4,13–15,17,18}

The role of forceps size has not been well defined.¹⁹ The two most common types of forceps for TBLB are the cupped forceps and the alligator forceps.^1,3 While several studies have compared alligator forceps to cupped forceps, none have shown that one tool is superior to the other.^1,3,4,15 Many previous studies that addressed the efficacy of TBLB did not mention the size of the forceps.^12,20,21 Several studies have shown that the use of large forceps can improve tissue acquisition and potentially improve diagnostic yield.²² Loube et al prospectively compared the diagnostic yield of TBLB using large forceps (3 × 2 × 0.9 mm) and small forceps (2 × 1.5 × 0.6 mm). They reported that larger forceps provided more and larger tissue without an increase in postbiopsy bleeding.²² A study done by Poletti et al showed that use of jumbo forceps (cup size 9 × 3 × 3 mm; Model K 011340, Diflex, Rietheim‐Weilheim, Germany) allowed for a larger size of tissue biopsies and an increase in diagnostic yield. These forceps required the use of a rigid bronchoscope. There was an increased risk of bleeding compared with TBLB done with flexible bronchoscopy, but this was easily controlled with the use of a Fogarty balloon.¹¹ The studies that used larger forceps noted acquisition of larger tissue samples but an increased risk of major complications such as hemorrhage.^11,22 In another study, a direct comparison of three different forceps sizes showed no difference in the quality of tissue acquisition.²³

In a study by Trulock et al, 203 bronchoscopies were done for TBLB using a 2 mm fenestrated forceps. They described a pneumothorax rate of 0 and an excessive bleeding rate of 3.9%.¹⁶ In another study, Eslaminejab et al compared cupped forceps vs alligator forceps but did not discuss the size of the forceps or the complication rate.²⁰ Wahidi et al performed an animal study comparing conventional forceps (1.8 mm wide, 2 mm long, cup capacity 3 mm³; Onmed Corporation, Utica, NY) vs hot forceps (2.2 mm wide, 2.6 mm long, 5.1 mm³; Olympus, Inc., Center Valley, PA). They did not find any difference in the sample size. They also did not report complication rates.²¹

To date, no guidelines have standardized the acquisition of lung tissue by TBLB. The use of TBLB for tissue acquisition seems to have been largely replaced by the more invasive approach of cTBLB. The procedural technique for cTBLB has not been standardized, and the variation in approaches raises concerns for safety and competency.¹¹ The mortality rate from cTBLB can be up to 0.3%. The rate of pneumothorax can be as high as 30%.²⁴ In the study by Ravaglia et al, the pneumothorax rate was 20.2% with 15.5% requiring drainage.²⁵ The bleeding rate was more difficult to assess because of the lack of a standard scale. However, previous papers have used a scoring system to determine the severity of bleeding (Table 1).^25,26 It can be argued that all cTBLB are subject to moderate bleeding because of the recommendation to use an occluding balloon after each biopsy.^11,26 Ravaglia et al reported that no interventions were required to control bleeding in the study. It is possible the bleeding rate could have been underrepresented due to the prophylactic use of the Fogarty balloon. Overall, the complication rate for bleeding can be as high as 14.7%.²⁵

Another important consideration is visualization of the airway. After cryobiopsy is performed, airway visualization is lost temporarily as the cryoprobe and the flexible bronchoscope are removed en bloc. Dislodgement of the Fogarty balloon may not be immediately identified with the lack of visualization. This puts the patient at high risk for unrecognized bleeding. If there is significant bleeding, it may prove difficult to navigate to the culprit airway and attempt to stop the bleeding with the flexible bronchoscope. Using our approach, the bronchoscope remains wedged in the airway through which the biopsy is performed. This allows for immediate recognition of the bleeding and rapid intervention to control and stop it.

Our pneumothorax rate fell within the same range (5%) as previously reported.^{1–4,12–16} Only one patient required insertion of a chest tube, which was removed within 24 hours. One patient had bleeding that was easily controlled with ice saline lavage and suction. No escalation of care was noted. Of the 35 patients, 32 had pathologic findings on their biopsy specimens. The correlation with clinical and radiographic settings is not discussed in this report nor the therapeutic interventions taken after biopsy results. This report addresses the feasibility and safety profile of large-forceps TBLB. Further larger prospective studies are needed to address the diagnostic yield.

Given the uncertainty with cTBLB and the increased morbidity and mortality associated with surgical lung biopsy, it may be reasonable to consider transbronchial biopsy with a large forceps as an alternative initial diagnostic procedure in patients with nonspecific interstitial lung disease patterns on CT of the chest. Our retrospective study shows the feasibility and acceptable safety profile of this approach, but larger randomized trials are needed.