Adiscrete lung lesion may be classified as a nodule (0.2 to 3.0 cm) or a mass (>3.0 cm). Flexible bronchoscopy (FB) is frequently performed in patients with such lesions to establish a diagnosis.1 Although the diagnostic yield of endobronchially visible lesions is greater than 90%,2 the yield of solitary lung lesions without endobronchial abnormalities varies from 18% to 75%.1,3–5 Fluoroscopic guidance is frequently used during FB to improve the diagnostic yield; however, its use is not without limitations. First, it can expose both patients and medical staff to radiation. In addition, fluoroscopy is not routinely available in many bronchoscopy units. Many FB examinations are being performed without fluoroscopy; however, little has been reported regarding the diagnostic yield of FB without fluoroscopic guidance. The aim of this study was to evaluate the diagnostic yield, the factors affecting the diagnostic yield, complications, and safety of FB in patients with peripheral lung lesions without using fluoroscopic guidance.
We retrospectively reviewed the medical records of all the patients who underwent FB at St. Paul's Hospital of the Catholic University of Korea between March 1999 and May 2004. The Institutional Review Board of St. Paul's Hospital approved this study. One hundred fifty-one patients had lung lesions without endobronchial abnormalities. Among these, 47 patients were excluded because of film losses or inadequate medical records, and an additional 11 patients were excluded because the lesions were deemed inactive in clinical follow-up (Fig. 1).
Chest x-ray and computed tomography (CT) scan were taken in all patients before FB. The radiographic appearance of the lesions was analyzed by a radiologist based on a chest CT scan, and the largest of these dimensions was used to define nodule size. The shape of the lesions was classified as sharp, fuzzy, or cavitary. The margins of the lesions were classified as round or ill defined. We divided the area around the hilum on the chest x-ray into 3 elliptical areas to define the inner, middle, and outer thirds of the lung. The part of the mass that was closest to the carina was used as the reference point.
All the bronchoscopies were performed by the same physician. After the administration of 0.5 mg of atropine sulfate and 50 mg of pethidine (intramuscular), patients inhaled lidocaine (4% solution) from a hand-held nebulizer for 5 minutes. Arterial oxygen saturation (SpO2) and heart rate were continuously monitored by pulse oximetry. Oxygen was administered through a nasal cannula, and the flow was adjusted upward from 1 L/min to maintain SpO2 greater than 90%. BF-1T30 and BF-1T240 bronchoscopes (Olympus, Tokyo, Japan) equipped with brushes and biopsy forceps were used. All procedures were performed through the transnasal or transoral route under local anesthesia. Midazolam was used in minimal amounts to achieve adequate sedation. After visualization of the vocal cords, lidocaine (1 mL of a 4% solution) was sprayed as needed. All segments of the bronchial tree were visualized. The bronchoscope was then advanced to the segment suspected to be the location of the mass according to the CT scan. No guidance technique [e.g., fluoroscopic guidance, CT fluoroscopy, endobronchial ultrasound (EBUS), or electromagnetic navigation] was used.
A cytology brush was advanced into the bronchus, and a few vigorous back-and-forth movements were made to collect a sample. The sample obtained by brushing was smeared on at least 3 slides, air dried, and sent for acid-fast bacilli and Papanicolaou staining. After brushing, a biopsy specimen was taken with standard-sized forceps. At least 3 good-sized specimens were obtained, placed in formalin, and sent for hematoxylin and eosin staining. After biopsy, 20 cc of saline was instilled and aspirated at least 3 times. A bronchial wash sample was sent for Papanicolaou (cytology), hematoxylin and eosin (cell block), and acid-fast bacilli staining and culture. Rapid on-site cytology evaluation (ROSE) was not available at our institution at that time.
Statistical analysis was carried out with the SPSS program (version 11.5). A χ2 test or the Fisher exact test and a one-way analysis of variance test were used appropriately to verify the statistical significance of the results. A P value of less than 0.05 was considered statistically significant.
Ninety-three patients were enrolled in this study. Patients whose bronchoscopic result was negative underwent additional diagnostic tests with CT-guided transthoracic needle aspiration (TTNA), video-assisted thoracoscopic surgery, or thoracotomy. Among these, 38 lesions were malignant (18 squamous cell carcinomas, 15 adenocarcinomas, 3 small cell carcinomas, 1 bronchoalveolar carcinoma, and 1 low-grade malignancy) and 46 were benign (30 cases of pulmonary tuberculosis, 9 cases of pneumonia, 5 cases of aspergillosis, 1 case of sarcoidosis, and 1 case of actinomycosis). Nine lesions were not confirmed and we deemed these patients as indeterminate by bronchoscopy (Fig. 1).
The overall diagnostic rate was 65%, and the diagnostic sensitivities of bronchoscopy for malignant and benign lesions were 68% and 74%, respectively. The yield of bronchoscopy according to lesion size is described in Table 1. The diagnostic yield was significantly higher for lesions >2 cm (70%) than for lesions ≤2 cm (11%; P <0.001; Fig. 2). Transbronchial lung biopsy (TBLB) was performed in 79 patients, bronchial washing (BW) was performed in all 93 patients, and 91 patients underwent bronchial brushing (BB). The diagnostic yield was 46% for TBLB, 29% for BW, and 29% for BB, and the total yield was 65%. The diagnostic yield of TBLB (46%) was higher than that of BW (29%; P=0.025) or brushing (29%; P=0.022). For benign lesions, the diagnostic yields were 35%, 32%, and 32% for TBLB, BW, and BB, respectively. For malignant lesions, the diagnostic yields were 70%, 32%, and 31% for TBLB, BW, and BB, respectively. The diagnostic yield of TBLB for malignant disease (70%) was significantly higher than that for benign disease (35%; P=0.003; Table 2).
Table 3 shows the effect of shape and sampling method on diagnostic yield. No difference in diagnostic yield was observed according to shape (sharp, 70%; fuzzy, 62%; cavitary, 63%). The yield of BW was 41% for sharp lesions, 28% for fuzzy lesions, and 16% for cavitary lesions. Although the yield of BW for sharp lesions showed a trend toward a higher diagnostic rate, the difference was not statistically significant (P=0.174).
Similarly, no difference in diagnostic yield was observed according to the characteristics at the margins (round, 67%; ill defined, 68%; Table 4). No significant difference in diagnostic yield was observed according to the anatomic lobe of the lesion or among the upper, middle, and lower lobes (Table 5). The diagnostic yield according to the distance from the hilum was also statistically insignificant (Table 6).
Pneumothoraces and significant bleeding developed in 4.3% (4 of 93) and 2.2% (2 of 93) of the patients, respectively. None of the patients required closed tube drainage or intubation.
This study showed that lung lesions not visible through the bronchoscope can be diagnosed with accuracy by FB without fluoroscopic guidance. To improve the diagnostic yield of peripheral lesions, biplanar or uniplanar fluoroscopy is widely used, with reported yields of 51% to 73%1,3,6–9 and an apparent dependence on lesion size.1,6,9,10 Although there was no control group in this study, our overall diagnostic yield (65%) is comparable to that reported in earlier studies using fluoroscopy. The drawbacks of fluoroscopy include radiation exposure, longer procedure time, and the necessity of fluoroscopy equipment and a larger workspace. In terms of safety, the complication rates for pneumothorax, fever, and hemoptysis are similar when comparing transbronchial biopsy with and without fluoroscopy.11 In our study, no serious complication occurred, even without fluoroscopy.
There have been a few studies about the diagnostic yield of bronchoscopy without fluoroscopy. Anders et al11 showed that TBLB without fluoroscopy was safe and that the diagnostic yield was good (52%). However, no information about the lesion size or presence of endobronchial lesion was available. In a report with regard to a 5-year experience of 174 TBLBs performed without fluoroscopy in patients with interstitial lung disease or a suspicion of sarcoidosis, the diagnostic rate was 88%.12 However, there was also no information about the characteristics of the lesion. Lee et al13 showed a rate of 86% in the diagnosis of peripheral pulmonary tumors with the technique of immediate cytologic examination of multiple brushings using the Riu stain. In this study, tumor size did not affect the diagnostic yield (83% for ≤3 cm, 88% for >3 cm). In a study by Paone et al,14 TBLB without fluoroscopy showed a sensitivity of 55.4%, which was greatly affected by lesion size (23% for ≤2 cm, 77.3% for >3 cm). Our result was well compatible with the report of Paone et al. The overall diagnostic yield was 65% and was affected by the lesion size.
There are several potential reasons why fluoroscopic guidance did not improve diagnostic yield. First, a CT scan is sufficient as a location guide. Before performing FB, we determined the exact location of the lesion so that we could approach the proper segment without fluoroscopy. The potential role of CT scan for enhancing the bronchoscopic yield has been reported. Naidich et al15 showed that the presence of a bronchus on CT scan, which leads directly to a solitary pulmonary nodule (the so-called “bronchus sign”), is valuable for predicting the success of TBB. Several researchers have also advocated the use of thin-section CT scans to predict the value of FB for diagnosing peripheral lung lesions.16,17 Second, it is not always possible to approach a peripheral lesion with forceps. Although the location of the lesion can be confirmed by fluoroscopy, some peripheral lesions in subsegments cannot be accessed. Third, fluoroscopy may be limited for detecting small lesions. In this case, fluoroscopic guidance does not improve diagnostic yield.
Our study confirmed that the diagnostic yield of FB is dependent on lesion size (11% for ≤2 cm, 70% for>2 cm). Published studies have consistently shown that lesion size influences the diagnostic accuracy of bronchoscopy. In particular, the yield from bronchoscopy is low in lesions measuring <2 cm,1,6,10 and our results are consistent with these earlier reports.
With the increase in computer power and advances in CT technology, it has become possible to use CT scan in real time to guide the bronchoscopist with greater precision than what can be expected using fluoroscopy alone.18 Tsushima et al19 compared the diagnostic yield of CT fluoroscopy with traditional fluoroscopy during bronchoscopy, but the diagnostic yield was only improved for small-sized nodules. In a randomized, controlled study of CT fluoroscopy-guided bronchoscopy versus conventional fluoroscopy-guided bronchoscopy for diagnosing peripheral lung lesions, the diagnostic sensitivities were also similar (71% vs. 76%; P=1.0).20 In addition, CT fluoroscopy is much more time consuming and costly than fluoroscopy, exposes medical personnel and patients to radiation, and requires several safety procedures to avoid radiation effects.19,21
Recently, new technologies, such as EBUS and electromagnetic navigation, have become available. In a prospective, randomized study, EBUS-driven TBB showed a significantly higher diagnostic yield (78.7%) than TBB alone (55.4%; P=0.004).14 However, the analysis of a subset of individuals with lesions >3 cm in diameter showed no difference between the 2 groups (82.8% for EBUS-driven TBB vs. 77.3% for TBB; P >0.05).14 EBUS is also costly, requires regular probe replacement, and poses a challenge in selecting the bronchial branch of interest.22 Electromagnetic-guided bronchoscopy is an emerging technology that allows access to peripheral pulmonary lesions not accessible through traditional bronchoscopy. This allows the bronchoscopist to virtually navigate to a selected target with high precision.18 In a study by Eberhardt et al,23 the diagnostic result was independent of lesion size and lobar distribution. However, the overall diagnostic yield was 67% and the yield of lesions >20 mm was 68.5%; our results were similar (65% and 70.2%, respectively). However, these electromagnetic navigation systems are also costly. For example, the super Dimension/Bronchus (super Dimension, Inc., Plymouth, MN) system for electromagnetic navigation bronchoscopy costs $129,450 and the disposable sensor probes together with the extending working channel cost $995.24
Although TTNA may reach a diagnostic yield of 82% to 96%,25,26 it is associated with increased rates of pneumothorax (23% to 44%).27,28 In 1 report, 38% of postbiopsy pneumothorax patients (45 of 118) required chest tube insertion.29 Rarely, air embolism complication30 or needle tract implantation of tumor after TTNA31 can occur. An FB examination can avoid the need for TTNA in many cases.
Some earlier studies have shown regional differences in diagnostic yield.1,3,32 However, our results showed no significant difference between lobes or among the inner, middle, and outer thirds. All of the previously mentioned studies used fluoroscopy for guidance, and whether this may affect results requires further study.
TBLB, BB, and BW are all important for diagnosis. These sampling procedures were complementary for improving the diagnostic yield of bronchoscopy. In 43% of patients, only 1 sample was diagnostic. Among these 3 methods, TBLB showed the highest diagnostic yield (TBLB, 46%; BW, 29%; and BB, 29%). Baaklini et al6 also showed a similar trend (TBLB, 52%; BW, 40%; and BB, 41%). A subanalysis of our data showed a high diagnostic yield for TBLB (70%) in malignant disease, suggesting that TBLB should be preferentially considered when evaluating lesions suspected of malignancy.
This study had some limitations. First, bronchoscopy was performed by only 1 person. This is essentially a 1 person experience, and there is a possibility that the diagnostic yield might have been influenced by the technique of the bronchoscopist. Second, this was neither a prospective nor a controlled study. This study had no control group, so the comparison of the diagnostic yield was made using published data. However, FB was performed with the same protocol by the same physician, and all the 3 sampling methods were performed except in patients with bleeding or other contraindications. Third, our study did not have access to ROSE, which improves diagnostic efficacy independent of localization, lesion histology, and operator experience.33 However, ROSE is costly and requires a longer procedure time. In addition, ROSE is still not routinely available in many centers, so our results are representative of a large portion of pulmonary practice.
In summary, FB sampling was safe with a relatively high rate of accuracy for the diagnosis of peripheral lung lesions >2 cm. When we took a CT scan and determined the exact location of the lesion before FB, the diagnostic yield of FB without fluoroscopic guidance was comparable with that reported earlier using fluoroscopy. Size was an important determinant of diagnostic yield. For lesions>2 cm, sampling procedures using FB should be performed first, which may allow the physician to avoid other diagnostic procedures, such as TTNA. However, FB with guidance or other diagnostic procedures should be considered for lesions of ≤2 cm.
1. Chechani V. Bronchoscopic diagnosis
of solitary pulmonary nodules and lung masses in the absence of endobronchial abnormality. Chest. 1996;109:620–625.
2. Dreisin RB, Albert RK, Talley PA, et al. Flexible fiberoptic bronchoscopy in the teaching hospital: yield and complications. Chest. 1978;74:144–149.
3. Cortese DA, McDougall JC. Biopsy and brushing of peripheral lung cancer with fluoroscopic guidance. Chest. 1979;75:141–145.
4. White CS, Templeton PA, Hasday JD. CT-assisted transbronchial needle aspiration: usefulness of CT fluoroscopy. Am J Roentgenol. 1997;169:393–394.
5. White CS, Weiner EA, Patel P, et al. Transbronchial needle aspiration: guidance with CT fluoroscopy. Chest. 2000;118:1630–1638.
6. Baaklini WA, Reinoso MA, Gorin AB, et al. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest. 2000;117:1049–1054.
7. Reichenberger F, Weber J, Tamm M, et al. The value of transbronchial needle aspiration in the diagnosis
of peripheral pulmonary lesions. Chest. 1999;116:704–708.
8. Bilaceroglu S, Kumcuoglu Z, Alper H, et al. CT bronchus sign-guided bronchoscopic multiple diagnostic procedures in carcinomatous solitary pulmonary nodules and masses. Respiration. 1998;65:49–55.
9. Radke JR, Conway WA, Eyler WR, et al. Diagnostic accuracy in peripheral lung lesions: factors predicting success with flexible fiberoptic bronchoscopy. Chest. 1979;76:176–179.
10. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis
of suspected lung cancer: summary of published evidence. Chest. 2003;123:115–128S.
11. Anders GT, Johnson JE, Bush BA, et al. Transbronchial biopsy without fluoroscopy: a seven-year perspective. Chest. 1988;94:557–560.
12. de Fenoyl O, Capron F, Lebeau B, et al. Transbronchial biopsy without fluoroscopy: a five year experience in outpatients. Thorax. 1989;44:956–959.
13. Lee CH, Wang CH, Lin MC, et al. Multiple brushings with immediate Riu's stain via flexible fibreoptic bronchoscopy without fluoroscopic guidance in the diagnosis
of peripheral pulmonary tumours. Thorax. 1995;50:18–21.
14. Paone G, Nicastri E, Lucantoni G, et al. Endobronchial ultrasound-driven biopsy in the diagnosis
of peripheral lung lesions. Chest. 2005;128:3551–3557.
15. Naidich DP, Sussman R, Kutcher WL, et al. Solitary pulmonary nodules: CT-bronchoscopic correlation. Chest. 1988;93:595–598.
16. Gaeta M, Pandolfo I, Volta S, et al. Bronchus sign on CT in peripheral carcinoma of the lung: value in predicting results of transbronchial biopsy. Am J Roentgenol. 1991;157:1181–1185.
17. Bandoh S, Fujita J, Tojo Y, et al. Diagnostic accuracy and safety of flexible bronchoscopy
with multiplanar reconstruction images and ultrafast Papanicolaou stain: evaluating solitary pulmonary nodules. Chest. 2003;124:1985–1992.
18. El-Bayoumi E, Silvestri GA. Bronchoscopy for the diagnosis
and staging of lung cancer. Semin Respir Crit Care Med. 2008;29:261–270.
19. Tsushima K, Sone S, Hanaoka T, et al. Comparison of bronchoscopic diagnosis
for peripheral pulmonary nodule under fluoroscopic guidance with CT guidance. Respir Med. 2006;100:737–745.
20. Ost D, Shah R, Anasco E, et al. A randomized trial of CT fluoroscopic-guided bronchoscopy versus conventional bronchoscopy in patients with suspected lung cancer. Chest. 2008;134:507–513.
21. Herth FJ, Becker HD, Ernst A. Ultrasound-guided transbronchial needle aspiration: an experience in 242 patients. Chest. 2003;123:604–607.
22. Makris D, Scherpereel A, Leroy S, et al. Electromagnetic navigation diagnostic bronchoscopy for small peripheral lung lesions. Eur Respir J. 2007;29:1187–1192.
23. Eberhardt R, Anantham D, Herth F, et al. Electromagnetic navigation diagnostic bronchoscopy in peripheral lung lesions. Chest. 2007;131:1800–1805.
24. Eberhardt R, Anantham D, Ernst A, et al. Multimodality bronchoscopic diagnosis
of peripheral lung lesions: a randomized controlled trial. Am J Respir Crit Care Med. 2007;176:36–41.
25. Geraghty PR, Kee ST, McFarlane G, et al. CT-guided transthoracic needle aspiration biopsy of pulmonary nodules: needle size and pneumothorax rate. Radiology. 2003;229:475–481.
26. Kazerooni EA, Lim FT, Mikhail A, et al. Risk of pneumothorax in CT-guided transthoracic needle aspiration biopsy of the lung. Radiology. 1996;198:371–375.
27. Li H, Boiselle PM, Shepard JO, et al. Diagnostic accuracy and safety of CT-guided percutaneous needle aspiration biopsy of the lung: comparison of small and large pulmonary nodules. Am J Roentgenol. 1996;167:105–109.
28. Laurent F, Michel P, Latrabe V, et al. Pneumothoraces and chest tube placement after CT-guided transthoracic lung biopsy using a coaxial technique: incidence and risk factors. Am J Roentgenol. 1999;172:1049–1053.
29. Westcott JL. Direct percutaneous needle aspiration of localized pulmonary lesions: result in 422 patients. Radiology. 1980;137:31–35.
30. Westcott JL. Air embolism complicating percutaneous needle biopsy of the lung. Chest. 1973;63:108–110.
31. Wolinsky H, Lischner MW. Needle track implantation of tumor after percutaneous lung biopsy. Ann Intern Med. 1969;71:359–362.
32. Stringfield JT, Markowitz DJ, Bentz RR, et al. The effect of tumor size and location on diagnosis
by fiberoptic bronchoscopy. Chest. 1977;72:474–476.
33. Uchida J, Imamura F, Takenaka A, et al. Improved diagnostic efficacy by rapid cytology test in fluoroscopy-guided bronchoscopy. J Thorac Oncol. 2006;1:314–318.