Is bronchoscopic lung biopsy helpful in the management of patients with diffuse lung disease?

Biopsies of the lung have been obtained via bronchoscopy for >40 yrs 1–3. Several studies have reported the diagnostic yield and complications of bronchoscopic lung biopsy (BLB) in various patient populations 4, 5. The purpose of the present study was to determine whether information obtained from BLB is useful to clinicians, and how this information is used in the management of patients with diffuse pulmonary disorders.

Many of the published reports have focused on the role of BLB in the diagnosis of diffuse pulmonary diseases and the accuracy of histological diagnosis. The present study, in contrast to earlier studies, was designed to evaluate how BLB results are used by clinicians. The main aim of the study was to assess whether the results of the BLB were clinically useful in the management of patients with diffuse pulmonary disorders.

METHODS

The study was a retrospective analysis of patients who underwent BLB at the Mayo Clinic (Rochester, MN, USA) between July 1, 2002 and June 30, 2004. Subjects were identified through a medical records database by searching for the term “closed lung biopsy”. All patients authorised their records to be reviewed. The institutional review board approved the study. BLB was defined as a biopsy performed via bronchoscopy with the intention of obtaining adequate parenchymal lung tissue for meaningful histological analysis. By this definition, attempts to biopsy a lung mass, solitary nodule or lung cavity were excluded. Indication for BLB was obtained from the bronchoscopy report. All BLBs were performed with fluoroscopic guidance. Procedures were performed or supervised by a group of experienced, dedicated bronchoscopists. Medical records were reviewed to determine how the results of BLB impacted upon patient care. BLB was considered useful if: 1) it resulted in a specific clinical diagnosis; 2) a specific management decision was made based on the biopsy result; or 3) certain pathological processes were excluded on the basis of the biopsy result and other clinical information. BLB was considered unhelpful in patients who had a specific diagnosis from other procedures or biopsies, or those in whom the procedure failed to obtain lung tissue. Radiographic reports and clinical notes following bronchoscopy were reviewed for evidence of post-procedure pneumothorax.

RESULTS

During the study period, 603 patients underwent a total of 651 BLBs. During this period, ∼3,300 bronchoscopies were carried out at the Mayo Medical Center. The median (range) patient age was 60 (10–93) yrs, and there were 355 females (54.5%). Indications for BLB are shown in table 1⇓. A total of 54 BLBs were performed in 16 lung transplant recipients for the indications of pulmonary infiltrate or transplant surveillance. Histopathological diagnoses are shown in table 2⇓. Biopsy results were considered helpful in 494 (75.9%) out of the 651 procedures. Of these, 249 (38.2% of all BLBs) provided clinically useful histopathological diagnoses and the remainder were helpful in excluding certain disorders. In total, 157 (24.1%) of the biopsies were considered not helpful. In 52 (8% of all BLBs), no lung parenchyma was obtained.

No specific diagnostic abnormality was identified in 107 (16.4%) of all biopsies. This finding was considered helpful in 59 (55.1%) out of the 107, as the clinician felt that specific pathological processes were ruled out and no further work-up was pursued. A total of 48 biopsies in 47 patients that identified no diagnostic abnormality were felt to be unhelpful (48 out of 107; 44.9%). Of these patients, 34 had additional diagnostic tests performed that resulted in a specific diagnosis (34 out of 47; 72.3%).

When the BLB result was considered unhelpful, open lung biopsy was performed in 44 (28.6%) out of 154 patients. A specific diagnosis was established by a bronchoscopic procedure performed at the time of BLB (cytology, transbronchial needle aspiration, endobronchial biopsy, cultures of bronchoalveolar lavage fluid or bronchial washings) in 23 out of the 157 BLB procedures with unhelpful results (14.6%).

Malignancy was ultimately diagnosed in 94 (15.6%) out of the 603 patients who underwent BLB. In 66 out of 94 (70.2%), the diagnosis was provided by BLB. Primary lung cancer was diagnosed in 66 (10.9%) out of 603 patients, and metastatic malignancy in 28 (4.6%) out of 603. The diagnostic rate of BLB was 72.7% for primary lung cancer and 64.3% for metastatic malignancy.

Of all BLB procedures, pneumothorax occurred in eight (1.2%) out of 651. Other complications including bleeding and death were not specifically identified as part of this study.

DISCUSSION

BLB, also known as transbronchoscopic or transbronchial lung biopsy, refers to the bronchoscopic technique of obtaining pulmonary parenchymal tissue for histological analysis. At the Mayo Clinic in 1965, Andersen et al. 1 described the rigid bronchoscopic technique of BLB in 13 patients. Subsequent studies reported the results of BLB using the rigid bronchoscope 2–8. Among the first 450 cases of BLB performed via the rigid bronchoscope, lung tissue was obtained in 84% of patients with diffuse lung diseases 3. The introduction of the flexible bronchoscope in the late 1960s increased the popularity of the technique and demonstrated that BLB with the flexible instrument could be obtained with minimal mortality and morbidity 4, 9–13.

The initial experience reported positive biopsy results in 60% of patients who had BLB via flexible bronchoscopy for diffuse bilateral shadows or multiple opacities 5. Subsequent experience described in several studies reported positive results in 82% of cases 9, 10, 14. The substantial clinical usefulness and safety of BLB in diffuse pulmonary disorders has been demonstrated in many studies 15, 16. As a result, BLB is a well-established diagnostic technique used by almost all bronchoscopists, and the flexible bronchoscope is used almost exclusively. In a survey of 1,800 North American bronchoscopists, nearly 70% reported that they performed BLB routinely in diffuse lung disease in nonimmunocompromised patients 17.

By definition, BLB denotes biopsy of lung or pathological processes occurring within the pulmonary parenchyma. Biopsy of peripheral nodules originating in the bronchial wall does not represent BLB. Nevertheless, the term BLB is loosely used in clinical practice as well as literature to describe biopsy of any bronchoscopically invisible lesion. As a result, the interpretation of diagnostic yield from “BLB” of diffuse and localised lesions becomes difficult 18. In the current authors’ analysis, results of biopsies of solitary nodules were excluded and patients who had radiological features of patchy or widespread diffuse parenchymal disease were included. Most, if not all, patients in the present study underwent chest computed tomography evaluation prior to bronchoscopy to guide BLB. However, a standardised algorithm was not used for work-up prior to bronchoscopy.

There is variability in defining the term “diffuse lung disease”. In some cases, this term is used to describe bilateral, multilobar parenchymal changes; however, the present authors’ analysis included any ill-defined radiographic lesion, reasoning that a pathological process can be diffuse in a localised area of pulmonary parenchyma. As mentioned previously, BLBs of these types of lesions are performed with the intent to obtain parenchymal lung tissue.

Diffuse interstitial lung disease caused by either benign or malignant processes is a common indication for BLB 19–22. The most common indication for BLB in the current authors’ study was pulmonary infiltrate (patchy or widespread) in 81.9% of cases, followed by multiple pulmonary nodules or nodular infiltrate in 9.1%. Patients with interstitial lung disease were frequently included in the pulmonary infiltrate group, as this was the main indication for BLB listed on the procedure report. Similarly, lung transplant recipients whose indication for BLB was “pulmonary infiltrate” were also included in the group, and those without specific radiographic abnormalities were included in the “lung transplant recipient surveillance” group.

When BLB was introduced into clinical practice, a positive biopsy using the BLB technique was defined as diagnostic histology, histology that supported a diagnosis, or histology consistent with the final diagnosis 4. Indeed, most of the published studies have focused on the diagnostic accuracy of histological analysis of BLB in patients with diffuse lung disorders. In contrast to the earlier reports on BLB, the present study focused on how BLB results are used by clinicians. The main aim of the current study was to assess whether the results of the BLB were clinically useful in the management of patients with diffuse pulmonary disorders. The results of the present study indicate that BLB is a clinically useful test in ∼75% of procedures. The current analysis showed that of the 25% of BLBs that were clinically unhelpful, the main reason for failure in approximately one-third of these patients was the absence of pulmonary parenchyma, or an inadequate quantity of lung parenchyma, in the biopsy specimen for a meaningful histological analysis. While it is difficult to enumerate every factor underlying this failure, various factors may have contributed to the failure in obtaining adequate lung parenchyma. Some of the common reasons mentioned by the bronchoscopists included excessive patient cough, bleeding, and inadequate placement of biopsy forceps.

Inability to obtain optimal or adequate pulmonary parenchymal specimens is a common problem even when fluoroscopic guidance is used. Proper equipment, technique and use of fluoroscopy will enhance the chance of collecting good biopsy specimens 15. Previous studies also noted the problem of inadequate lung tissue from BLB in up to 20% of patients 1, 3.

Bronchoscopic biopsy of very localised lesions yields a diagnostic rate of ∼60% in primary lung cancer and of ∼50% in metastatic cancer, when these tumours present as peripheral lung nodules 18. Biopsy of lesions >2.0 cm in diameter provides a diagnostic yield in >60% of cases, whereas lesions <2.0 cm in diameter yield a diagnosis in <25% of cases 18. Diagnostic rates are likely to be lower if nodular or localised lesions are caused by nonmalignant processes. In the present cohort of patients with patchy or widespread diffuse parenchymal disease, malignancy was ultimately diagnosed in 15.6%. The diagnostic rate of BLB was 72.7% in primary lung cancer and 64.3% in metastatic cancer.

It is not uncommon for BLB pathology results to return without diagnostic abnormality. It can be difficult to know whether this is due to sampling error, or whether there truly is an absence of significant pathology. In the current study, an adequate lung parenchymal biopsy without a specific diagnostic abnormality was considered clinically helpful in 55% of the patients.

The current study is limited by its retrospective nature, and the difficulty in determining how results from BLB were used. The present authors attempted to follow strict criteria for definitions of usefulness or unusefulness; however, in some cases a degree of subjectivity was required. The bronchoscopy reports did not uniformly report the number of biopsies taken, so the current authors were unable to comment on the relationship between number of biopsies and diagnostic yield or clinical utility.

Since the 1990s, high-resolution computed tomography and video-assisted thoracoscopic lung biopsy have been emerging techniques in establishing the diagnosis of diffuse lung disorders. Bronchoalveolar lavage has also emerged as an important diagnostic tool that has obviated the need for bronchoscopic lung biopsy in many clinical conditions. Further improvements in these and other techniques may lead to a decline in the need for bronchoscopic lung biopsy. In the USA alone, >500,000 bronchoscopies are performed each year 23, and ∼15% of these procedures include bronchoscopic lung biopsy 24, 25. It is clear that bronchoscopic lung biopsy remains an important diagnostic method for the evaluation of patients with diffuse lung diseases 15, 16.