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Ann Thorac Surg 1998;65:198-202
© 1998 The Society of Thoracic Surgeons

Original Articles: General Thoracic

The Role of Open Lung Biopsy in the Management and Outcome of Patients With Diffuse Lung Disease

Mordechai R. Kramer, MD, Neville Berkman, MBBCh, Bella Mintz, MD, Simon Godfrey, MD, PhD, Milton Saute, MD, Gail Amir, MBBCH

Institute of Pulmonology, Hadassah University Hospital, Hebrew-University-Hadassah Medical School, Jerusalem, Israel
Department of Anesthesiology, Hadassah University Hospital, Hebrew-University-Hadassah Medical School, Jerusalem, Israel
Department of Pathology, Hadassah University Hospital, Hebrew-University-Hadassah Medical School, Jerusalem, Israel,
Thoracic Surgery Unit, Carmel Medical Center, Haifa, Israel

Accepted for publication July 14, 1997.

Dr Kramer, Institute of Pulmonology, Rabin Medical Center (Beilinson Campus), Petach Tikva, Israel 49100.


   Abstract
Top
 Footnotes
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background. Open lung biopsy (OLB) has long been considered the gold standard for the diagnosis of parenchymal lung disease. With recent advances in computed tomographic imaging and diagnostic techniques (eg, bronchoscopy), we thought it necessary to reevaluate the role of OLB in the management of patients with interstitial lung disease.

Methods. We carried out a retrospective analysis of 103 OLBs performed at Hadassah University Hospital, Jerusalem, and Carmel Medical Center, Haifa, between 1980 and 1994. Data gathered included demographic information, underlying condition, indications for biopsy, diagnosis before biopsy, final diagnosis, change in therapy, and mortality. "Benefit" was defined as a change in therapy resulting in survival.

Results. There were 45 immunocompetent patients (group 1), 39 immunocompromised patients (group 2), and 26 children (group 3), 7 of whom were included in group 2 for analysis. Overall, a diagnosis was reached after OLB in 85% of patients. An unexpected diagnosis was reached in 52%, and a change in therapy was instituted in 46%. The overall mortality rate was 20%. In group 1, the mortality rate was 13%, and "benefit" from OLB was reached in only 18%. In group 2, the mortality rate was 39%, and "benefit" was achieved in 46%, and in group 3, the mortality rate was 12% and "benefit", 50%.

Conclusions. Open lung biopsy is an excellent diagnostic technique. In immunocompetent patients, the "benefit" is relatively low, as therapy (corticosteroids) is frequently used after biopsy. In immunocompromised patients, therapy changes substantially after OLB, but mortality is high. Therefore, OLB should be reserved for patients in whom the diagnosis is likely to lead to a change in therapy and in patients in whom the underlying condition has a reasonable prognosis according to the clinical impression by the attending physician.


   Introduction
Top
 Footnotes
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Open lung biopsy (OLB) is considered the best method for diagnosing parenchymal lung disease [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Nevertheless, despite recent advances in surgical techniques (ie, thoracoscopy), it is still considered an invasive procedure requiring general anesthesia and is associated with substantial morbidity and mortality [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. As with any diagnostic procedure where the benefit for the patient outweighs the risk, the procedure is justified. We evaluated retrospectively the results of 103 OLBs performed in our institutions and looked specifically at the therapeutic implications and outcome of patients after this procedure. We included three groups of patients with diffuse lung disease: patients without immunosuppression, patients with immunosuppression, and children with diffuse lung disease. Our goals were to assess the benefit from the biopsy in each group and to build an algorithm that will be of help in the future.


   Patients and Methods
Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
We analyzed the medical records of 103 patients who underwent OLB from 1980 to 1994 at Hadassah University Hospital, Jerusalem, and Carmel Medical Center, Haifa. Data retrieved from the records included demographic material, underlying condition, clinical presentation of the pulmonary disease, results of chest radiography, results of lung function testing, and specific diagnostic evaluation prior to OLB, including results of bronchoscopy (bronchoalveolar lavage and transbronchial biopsy [TBB]). Open lung biopsy was performed under general anesthesia through a short anterior thoracotomy in the third intercostal space. The site of the biopsy was decided on the basis of the chest roentgenograms or the computed tomographic scan. A biopsy specimen was taken from one or two lobes, and a stapling device (GIA Autosuture) was used for securing the pulmonary margins in most patients. The diagnosis before biopsy was compared with the result of OLB. Complications from OLB, including death, and the clinical course prior to discharge were recorded. We evaluated four variables: the therapy that was instituted (or stopped) after OLB; whether this therapy was different from what was planned before OLB; whether the change in therapy influenced the outcome, ie, mortality; and diagnostic "benefit" of the procedure, which was defined as a change in therapy resulting in survival of the patient.

Statistical analysis was done using the Fisher exact test for comparison between groups.


   Results
Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Overall, 103 patients, 47 female and 56 male, underwent OLB. Age ranged from 2 months to 85 years (mean age, 37 years). The patients were divided into three groups. Group 1 comprised 45 immunocompetent patients 14 to 85 years old (mean age, 56 years). Group 2 included 39 immunosuppressed (immunocompromised) patients 16 months to 68 years old (mean age, 31 years). The underlying condition is shown in Table 1. Thirty-one had hematologic disease, and 14 of them had undergone bone marrow transplantation. Six had solid tumors; 1, a solid-organ transplant, and 1, collagen vascular disease (systemic lupus erythematosus). Group 3 comprised 26 children (younger than 13 years), 4 of whom were less than 12 months old. Seven were immunosuppressed and were included in group 2 for analysis.


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  		Underlying Condition in Immunosuppressed Patients

 
Bronchoscopy was performed in 44 patients (43%) and TBB, in 23 (22%). Transbronchial biopsy was performed more frequently in the years 1990 to 1994 (30% to 50%) than in the preceding years of the study (0% to 15%).

Diagnosis
Table 2 lists the different diagnoses in each group. A specific diagnosis was achieved in 87 patients (84.5%), whereas in 15.5%, the diagnosis was either nonspecific or normal lung tissue. Infection accounted for 14% of patients, most of whom were in the immunocompromised group (13/15 patients). Malignancy was found in 12 patients (12%). Usual interstitial pneumonia and desquamative interstitial pneumonia were found in 22% of patients, mostly in the immunocompetent patients (groups 1 and 3). Bronchiolitis obliterans organizing pneumonia was diagnosed in 10 patients (10%). In 53 patients (52%), the diagnosis was unexpected or unknown prior to biopsy.


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  		Final Diagnosis

 
After OLB, no change in therapy was made in 56 patients (54%). In this group, 15 patients had been placed on a regimen of corticosteroids prior to biopsy. Most of these patients had a diagnosis of usual interstitial pneumonia or desquamative interstitial pneumonia. Table 3 indicates the changes in therapy after OLB.


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  		Effect of Biopsy on Therapy and Outcome

 
Complications and Mortality
Table 4 The overall complication rate was 25% (24% in group 1, 33% in group 2, and 23% in group 3). The in-hospital mortality rate was 20% (13% in group 1, 39% in group 2, and 13% in group 3). Causes of death were respiratory failure (10 patients), multiorgan failure (7), intracerebral hemorrhage (2), and pulmonary hemorrhage (2). Of the 14 patients who had had bone marrow transplantation and later underwent OLB, 8 (57%) died.


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  		Complications and Mortality from Open Lung Biopsy

 
Risk factors contributing to mortality were mechanical ventilation before biopsy (12/16), urgent (nonelective) biopsy (10/14), vasopressor therapy (5/7), renal failure (5/6), arterial oxygen tension of less than 60 mm Hg (19/58), and bleeding diathesis (3/5).

Role of Fiberoptic Bronchoscopy and Transbronchial Biopsy
Forty-four patients (43%) underwent bronchoscopy and 23 of them, TBB. Of the immunocompromised patients, 17 (44%) had undergone previous fiberoptic bronchoscopy, but only 6 had had TBB mostly because of coexistent thrombocytopenia or high positive end-expiratory pressure ventilation. Most of the fiberoptic bronchoscopies were performed in the years 1989 to 1994. Tissue obtained at TBB was adequate in 75% of patients. It was not diagnostic in half of them, and in the other half, although diagnostic, it did not fit the clinical impression, and OLB was performed. In only 2 patients was TBB performed twice, and it was nondiagnostic on both occasions. Overall, TBB or bronchoalveolar lavage was compatible with the final diagnosis in 15 of the 44 patients in whom it was performed. However, the primary physicians were not convinced this was the final diagnosis.


   Comment
Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
Open lung biopsy is considered the best method for reaching a correct and specific diagnosis in diffuse lung disease. Specific diagnosis was reached in 37% to 92% of patients in various series [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. However, despite advances in surgical techniques, particularly thoracoscopy, OLB still has substantial morbidity and mortality. Morbidity can affect up to 83% of patients, and mortality ranges between 0% and 60% depending on the population examined (Table 5). It is obvious that in sicker patients with a rapidly deteriorating condition, complication and mortality rates will be high, whereas in patients with mild disease, the procedure is relatively safe.


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  		Summary of Literature Review of Open Lung Biopsy

 
When considering OLB, the main issue is whether or not there is a practical benefit from an invasive diagnostic procedure. Table 6 summarizes our results in each group. Whereas the diagnostic yield was very high (98%) and morbidity and mortality were low in the immunocompetent group, the diagnosis was unexpected in about half, and therapy was changed after biopsy in 18% of patients only. This is due mainly to the fact that in many instances, corticosteroid therapy is the treatment of choice. Conditions such as usual interstitial pneumonia, diffuse interstitial pneumonia, bronchiolitis obliterans organizing pneumonia, sarcoidosis, hypersensitivity pneumonitis, or eosinophilic pneumonia all require steroid treatment if the patient is symptomatic [17]. If one of these conditions is suspected on clinical grounds, a therapeutic trial could be justified even without a definite tissue diagnosis. This is based on the fact that even after OLB was performed, administration of steroids was the common result. If no response is observed after the steroid trial, OLB could be reconsidered. Our findings in the immunocompetent host are similar to those of others [1][2][3].


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  		Diagnostic and Therapeutic Yield of Open Lung Biopsy1

 
A biopsy is appropriate when malignancy, particularly lymphoma, or an unusual infection is strongly suspected. If one considers benefit from the procedure to be a change in therapy leading to survival, only 18% of patients in group 1 had a significant yield from the procedure. We could not find in the literature similar information, as most series report only diagnostic yield and complication rate. Fig 1A proposes an algorithm for OLB in diffuse lung disease in immunocompetent patients. One can argue that some patients would like to know the diagnosis even if it will not change therapy or prognosis. The risk and benefit, however, should be explained carefully to the patient, and the decision should be based on that information.



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  		(A) Algorithm for diagnosis of diffuse lung disease in patients without immunosuppression. Trial of steroids (*) should be considered in patients with suspected clinical diagnosis of, eg, usual interstitial pneumonia, diffuse interstitial pneumonia, sarcoidosis, eosinophilic pneumonia, bronchiolitis obliterans organizing pneumonia, and hypersensitivity pneumonitis. (B) Algorithm for diagnosis of diffuse lung disease in immunocompromised patients. Prognosis (*) is based on the underlying condition. (BAL = bronchoalveolar lavage; TBB = transbronchial biopsy.)

 
In the immunocompromised host, the picture is totally different [4][5][6][7][8][9][10][11][12][13][14][15][16]. In our group 2, diagnostic yield was high (85%), and an unexpected finding was common (72%) (see Table 6). An unexpected diagnosis can lead to a change in therapy, including discontinuation of unnecessary medication, in many instances. Therapy is highly variable according to the biopsy finding and may include multiple antimicrobial, antineoplastic, and antiinflammatory medications as well as discontinuation of many drugs, some of which are highly toxic (eg, amphotericin B). Despite the high diagnostic yield, the patient outcome in group 2 was quite disappointing; 39% of the patients died after biopsy with no actual gain from the procedure. Patients who had had bone marrow transplantation did most poorly, as they represented eight (57%) of the 14 deaths after OLB. It is true that death in these patients is mostly a result of the underlying condition rather than a result of the biopsy, but one should consider the impact of adding a serious diagnostic intervention in a critically ill patient.

Despite the high mortality in the immunocompromised patients, the benefit (change of therapy with survival) was considerable (46%) and significantly higher than in the immunocompetent group (p < 0.005) (see Table 6). In other studies, mortality rates range from 25% to 65% and change in therapy, from 28% to 65% (see Table 5).

On the basis of our data, to obtain maximal benefit from the procedure, OLB should be performed only in patients with a reasonable prognosis and not in moribund patients (Fig 1B).

In the group of children, diagnostic yield was lowest (81%), unexpected diagnosis was lowest (31%), mortality was low (12%), and the therapeutic yield was substantial (50% "benefit"). This suggests that in children, the biopsy confirmed a suspected diagnosis and allowed a therapeutic intervention with more confidence. The difficulty of performing TBB in children is a major reason for performing OLB early in the course of the disease.

Bronchoscopy can serve as a less invasive method of diagnosis and has been used more frequently in recent years than previously [18][19][20][21]. Improved technique, larger biopsy forceps, and better monitoring equipment have reduced the need of OLB in our experience as well as the experiences of others [18][19][20]. Bronchoalveolar lavage is frequently used in the immunocompromised host to exclude infection [21]. A repeat fiberoptic bronchoscopy with TBB is always an option to obtain more tissue. However, OLB is required in some patients, eg those with severe thrombocytopenia, mechanical ventilation, high positive end-expiratory pressure, or nondiagnostic TBB.

In conclusion, we report our experience with OLB in 103 patients. In immunocompetent patients, OLB did not lead to a change in therapy in most instances, as the diagnosis indicated corticosteroid therapy. In immunosuppressed patients, however, the differential diagnosis was wide with a variety of therapeutic options. As mortality is extremely high in this group, a careful selection of patients with a reasonably good prognosis should be made. The decision should be based on the experience of the attending physician with reference to the underlying condition and the clinical impression of the patient’s condition (eg, performance status or Karnofsky score). Open lung biopsy should be reserved for patients in whom a diagnosis that might change therapy is suspected and the underlying condition does not have a high mortality. A trial of one or more less invasive procedures (eg, TBB) should always be considered unless a major contraindication exists.


   Footnotes
Top
 Footnotes
Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
This article has been selected for the open discussion forum on the STS Web site: http://www.sts.org/annals


   References
Top
 Footnotes
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

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