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1 Original Article Full text online at Value of lung biopsy in pulmonary diseases in children S. Al-Nassar, P. Kadamba, Z. Habib King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Correspondence: Dr. Saleh Al-Nassar, Section of Pediatric Surgery, Department of Surgery (MBC-40), King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia, ABSTRACT Purpose: Open lung biopsy (OLB) is claimed to be a sensitive tool for the diagnosis of interstitial lung disease. It is reported to be associated with significant morbidity and mortality. Aim: Evaluate whether lung biopsy helped us to make a specific diagnosis, it had resulted in change in therapy and assessment of its morbidity and mortality. Materials and Methods: This was a retrospective analysis of 91 lung biopsies performed in 83 patients between January 2000 and December These children were allocated to three groups: a. Primary pulmonary pathology (22), b. Immunocompromised (49) i. Primary immunodeficiency (10), ii. Postchemotherapy and BMT (39), c. Pulmonary metastases from solid tumors (20) Results: A specific diagnosis was reached in 87/91 children (95%), but this resulted in a change in therapy (excluding lung meet) in only 23/71 (32%). It is lower in those postchemo/bmt 8/39 (20.6%). Postoperative morbidity occurred in 11/91 (12%) but procedure-related morbidity was only (3.2%). Death within a month of the biopsy occurred in six children (6.5%), with one (1.1%) procedure-related. Conclusion: 1. OLB is a safe procedure at our institution. 2. OLB is a sensitive tool to determine the specific cause of pulmonary infiltrate. 3. Change in therapy expected to be only in 32% of patients and even lower in postchemotherapy and BMT children. KEY WORDS: Interstitial lung disease, open lung biopsy, thoracoscopy INTRODUCTION assisted thoracoscopic surgery have decreased the morbidity of lung biopsy. [7-9] Nevertheless, lung biopsy A child who presents with severe respiratory distress is still an invasive procedure associated with with diffuse infiltrates seen on the chest radiograph is significant morbidity and mortality, especially in often a diagnostic challenge. Empirical therapy is immunocompromised children. [4,10-12] frequently begun with a combination of antibiotics, antifungal therapy with or without steroids, based on Our aim of this review is to evaluate the yield of lung the clinical picture and the radiologic abnormalities. biopsy done at King Faisal Specialist Hospital and However, when there is no improvement in clinical or Research Centre, Riyadh, Saudi Arabia (KFSH and RC), radiologic findings, definitive diagnosis is required. Less to make a specific diagnosis in both immunocompetent invasive procedures such as bronchoscopy and bronchoalveolar and immunocompromised child, whether open lung lavage may be helpful in diagnosing infectious biopsy (OLB) resulted in change in therapy, to assess causes, [1] but not so in noninfectious causes and in some morbidity and mortality of the procedure and develops fungal infections, when a lung biopsy may be essential. strategies or find alternative to OLB.7 Lung biopsy is considered to be the gold standard for the diagnosis of parenchymal lung disease. [2-5] Recent MATERIALS AND METHODS advances in imaging techniques viz, high resolution computerized tomography have helped in accurate A retrospective review of 91 lung biopsies in 83 children localization of pulmonary lesions. [6] The improvements was performed at KFSH and RC, with the age range in pediatric anesthesia and the emergence of video- between 3 months to 15 years (median = 7.37 years), J Indian Assoc Pediatr Surg / Oct-Dec 2006 / Vol 11 / Issue 4 234

2 in the period between January 2000 and December The data collected demographic information, primary diagnosis, prebiopsy therapy, indication for OLB, pathological and microbiological diagnosis, type of surgical procedure, modification of therapy postbiopsy and morbidity and mortality of the procedure (within 30 days). Children were grouped into three groups: Group I: Primary pulmonary pathology children (22) Group II: Immunocompromised children (49): a. Primary immunodeficiency (ID) (10) b. Postchemotherapy and BMT (39) Group III: Pulmonary metastasis from solid tumor (20) In Group I, all children are immunocompetent with no underlying immunodeficiency or malignancy. Indication The trend later was to remove the chest tube after reexpansion of the lung on table with positive pressure ventilation, except when there was a risk of persistent air-leak/bleeding from the biopsy site and in ventilated patients. The biopsy tissue was subjected to regular histopathology, including special studies for acid-fast bacilli; fungus; cytomegalovirus (CMV); pneumocystis carinii and also the specific cultures. Change in therapy was instituted when indicated, based on the pathological/ culture results; and the outcome (benefit or otherwise) was analyzed. for OLB in this group primarily prolonged respiratory RESULTS distress with significant radiological abnormalities with or without oxygen dependency. In Group I, histological specific diagnosis reached in 21 (95%) with 10 (45%) unexpected diagnosis [Table 1]. Group II are those congenital primary immunodeficiency However, change in therapy as a result of OLB was in 11 common variable ID (2), bore lymphocytic syndrome (2), (50%). Two had Nissen fundoplication for lipoid severe combined ID (scid) (3), chronic granulometous disease, Chediak Higashi syndrome (1). The primary indication of OLB in this group is recurrent chest infection with persistent or worsening radiological signs. Group II b, are those children who was on chemotherapy and those postbonemarrow transplant (BMT): AML (12), ALL (16), lymphoma (2) and post BMT (9). Those patients usually had routine computed tomography (CT) scan of chest if they develop fever or chest symptoms or shows sign of sepsis. Group III (20) those patient suggestive of pulmonary metastatic lesion to solid tumor. Both Group I and II patients started first on emperic treatment before OLB, in the form of antibiotic, antifungal or steroids according to prebiopsy clinical and radiological diagnosis. Group III, all sent for biopsy based on suspecting metastatic lesion radiologically, either persistent lesions despite chemotherapy or lesions appeared during remission of solid tumors. These lesions should be three or less, to quality for OLB. pneumonia [Figure 1], Secondary to GER, one lobectomy, five steroid therapy for hemosiderosis [Figure 2] and sarcoidosis, two anti-tuberculous treatments and one septra and choriquine for streptomyces. For Group II a, specific histological diagnosis reached in 10 (100%) and tissue culture was positive in only five (50%) (bacterial-1; mycobacterial-1 [Figure 3]; fungal-1; a mixed growth of all three-1 and pneumocystis carinii- Table 1: Results summary Group Histological specific Change in diagnosis therapy I 21 (95) 10 (45) IIa 10 (100) 4 (40) IIb 38 (97) 8 (20) III 18 (90) N/A Overall 87/91 (95) 23/71 (32) Figures in parentheses are percentage Tissue culture 3 (30) 5 (50) 8 (20.5) 1 (5) 17/91 (18.7) The lung biopsy was performed under general anesthesia by thoracotomy (open lung biopsy - OLB) or by videoassisted thoracoscopic surgery. OLB was performed by a muscle-sparing mini-thoracotomy (n=56) through the 4 th / 5 th intercostals space. Thoracoscopic biopsy (n=28) was performed by using three ports - a 5/10 mm port for a 30 o telescope and two other 3.5/5 mm working ports, with (n=7) converted to open. Biopsy was taken using an endo-gia stapler or rarely with an endo-loop. A chest tube was left in situ for 24 hours in the initial cases. 235 Figure 1: Lung biopsy in this child found to have: both lipoid pneumonia with tuberculosis J Indian Assoc Pediatr Surg / Oct-Dec 2006 / Vol 11 / Issue 4

3 Figure 3: Lung biopsy prove miliary tuberculosis Al-Nassar S, et al.: Value of lung biopsy in pulmonary disease in children Figure 2: CT of a child diagnosed unexpected with: Idiopathic pulmonary hemosidrosis 1). Change of therapy in four (40%), (Three specific antifungal and one prolonged antibiotic treatment). In Group II b, specific histological diagnosis reached in 38 (97%) with tissue culture only in eight (20%) and only Table 2: Comparison between pre and postbiopsy tissue diagnosis in Group I Diagnosis Pre-biopsy Post-biopsy Lipoid pneumonia 6 5 Surfactant deficiency 2 2 Idiopathic pulmonary hemosidrosis 3 4 Sarcoidosis - 1 Bronchopulmonary dysplasia - 1 Bronchiolitis obliterans 4 - Interstitial pneumonia - 4 Niemann-pick disease - 1 Bronchiectasis - 1 Tuberculosis 1 2 Nonspecific/undiagnosed RDS 6 1 bronchopleural fistula (1) and septic shock in one, but procedure-related morbidity 3/91 (3.2%). Mortality was six (6.5%) (within 1 month), with only one (1.1%) procedure-related. DISCUSSION The causes of persistent and progressive distress in a child are many including interstitial lung disease, infections, chronic aspiration, pulmonary vascular disease, and other rare conditions. A specific diagnosis can frequently be made from the chest X-ray or CT scan appearance of the lung lesions and the appropriate therapy started. This may not be true in children occasionally, where the appearances on the imaging studies are nonspecific. [13] There is also a group of patients who have been started on empiric therapy, but are not responding to this type of treatment where there is in need for other mode of diagnostic tools. Children postchemotherapy particularly for leukemia and lymphomas and also those children who are postbone marrow transplant as well as other immunocompromised children like primary and secondary immunodeficiency, are at risk of developing a serious pulmonary complications. These children usually have severe and prolonged neutropenia and they will be at risk of developing opportunistic infections. With the widespread use of prophylactic antibiotics, antiviral drugs for CMV and Septran for pneumocystis carinii, there has been a significant decrease in the incidence of these infections as well as of their complications. Some centers even advocate the empiric use of antifungal therapy in the group of neutropenic patients with persistent fever and characteristic lesions of lung infection on CT scans. An optimal and safe means of obtaining lung tissue for diagnosis is debatable, but an open lung biopsy either by thoracotomy or thoracoscopy can be considered to be the best diagnostic tool. [2-5] We found, in our group of patients, it is safe and provide good volume of tissue for diagnostic purposes. Video-assisted thoracoscopic surgery provides a better and wider visibility of the lung eight (20%) children therapy was changed (six had started specific antifungal, Each one antiviral and prolonged antibiotic). In Group III, 13 (65%) were positive for metastatic lesion to solid tumor, five (25%) has infectious process and two (10%) negative explorations. So, Specific diagnosis reached in 18 (90%) [Table 2]. The overall specific histological diagnosis reached in 87/ 91 (95%) but change in therapy excluding lung metastasis 23/71 (32%). Tissue culture was positive in only 17/91 (18.7%) [Table 2]. Our morbidity was 11 children (12.1%), prolonged intubation (6), oxygen dependency (2), hematoma (1), J Indian Assoc Pediatr Surg / Oct-Dec 2006 / Vol 11 / Issue 4 236

4 surface, with less morbidity than the mini-thoracotomy. Also with the availability of finer instruments, VATS is now feasible even in the smaller group of children. We find that it is safe despite reports of high morbidity and mortality in other studies. The main issue when considering a lung biopsy is whether or not there is a practical benefit from the invasive procedure with its associated morbidity and mortality. This is especially true in sicker children with immunosuppression from chemotherapy/postbmt where the benefits should be weighed with the risks developed. We found that it is a good tool to reach a specific diagnosis and this is similar to other reports from other groups, but it is not as high when it comes to having a positive tissue culture. For that reason, specific change in therapy was not high as well. Floreani et al. have collected 14 reports of 625 patients where the total yield in immunocompromised patients was found to be ranging between 45-83%, however, when it comes to change in therapy, only 32% which conclude that lung morbidity and mortality compared to other series. We still continue to use lung biopsy as a tool for the purpose of diagnosing pulmonary infiltrate as it benefits around 30% of the patients in regard to change of therapy, however, it benefit the rest of the group in continuing using the same management and has given comfort to the treating physician to continue the same line of management. CONCLUSION We wish to reiterate that lung biopsy is a sensitive diagnostic tool to reach specific histological diagnosis (95%). However, it is only helpful in (32%) to make change in therapy. Change in therapy is less likely in those postchemotherapy and BMT, as yield in tissue culture, is lower compare to the rest of the group. Our morbidity and mortality are low and considered to be safe in our institution as procedure-related morbidity (3.2%) and mortality (1.1%). OLB still considered diagnostic and therapeutic in suspected lung metastasis. biopsy can only benefit as high as 30% in Earlier lung biopsy in the course of the disease may be immunocompromised children. [10] However, Kramer et considered before starting an empiric treatment al reported 46% change in therapy but mortality was as (antibiotic) to get higher tissue culture positive results. high as 39% for immunocompromised children. [2] Hayes- Jordan et al. has reported 63% survival. [4] But, these REFERENCES obviously are not procedure-related mortality. However, when we compared it to our overall morbidity was 12.1% 1. 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