|Year : 2005 | Volume
| Issue : 4 | Page : 116-118
Bronchoscopic lung biopsy for diagnosis of miliary tuberculosis
AN Aggarwal1, D Gupta1, K Joshi2, SK Jindal1
1 Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh., India
2 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh., India
A N Aggarwal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Miliary tuberculosis is often treated empirically in India in the absence of a positive diagnosis based on sputum examination. We investigated the role of fiberoptic bronchoscopy for diagnosis of this disease. Methods : Records of patients undergoing fiberoptic bronchoscopy and bronchoscopic lung biopsy, and diagnosed to have miliary tuberculosis, over a four year period were evaluated. Two to four lung biopsy specimens were obtained from each patient and examined microscopically after Hematoxylin-eosin and Zeihl-Neelson staining.
Results : Thirty one patients of miliary tuberculosis (19 men and 12 women) underwent fiberoptic bronchoscopy during the study period. No endobronchial abnormality was noted in any patient. Bronchoscopic lung biopsy yielded adeqaute specimen in all but one patient. Granulomatous inflammation was noted in 21 (67.7%) patients on histopathological evaluation of biopsy specimens; of them, acid-fast bacilli were demonstrated in one patient. One patient (3.2%) had normal alveolar architecture. In the other 8 patients (25.8%), nonspecific pulmonary interstitial inflammation and/or mild fibrosis were seen. Bronchial wash specimens showed acid-fast bacilli in only one patient; this patient also had granulomatous inflammation on lung biopsy. All patients tolerated bronchoscopy well and there were no procedure-related complications.
Conclusion: Bronchoscopic lung biopsy is a safe procedure and an effective method of establishing diagnosis of miliary tuberculosis in a majority of patients with this disease. Bronchial washings do not provide significant additional information in this regard.
Keywords: Miliary tuberculosis, Fibreoptic bronchoscopy, Lung biopsy, Diagnosis
|How to cite this article:|
Aggarwal A N, Gupta D, Joshi K, Jindal S K. Bronchoscopic lung biopsy for diagnosis of miliary tuberculosis. Lung India 2005;22:116-8
| Introduction|| |
Pulmonary tuberculosis is a major health problem in India. Although most patients can be diagnosed based on sputum examination alone, a significant proportion need additional workup. Miliary tuberculosis is one such problem. It results from hematogenous dissemination of mycobacteria to various organ systems (including lung) and gets its name from the consequent small and discrete disease foci, usually of the size of millet seeds (1-2 mm). Clinical presentation is variable and ranges from an insidiously progressive febrile condition with constitutional features to a rapidly progressive and life-threatening acute respiratory distress syndrome.  Because most patients with this form of tuberculosis have negative sputum smears, diagnosis is often missed or delayed. Several patients may receive empirical antitubercular therapy without additional workup based purely on the characteristic miliary pattern on chest radiographs. 1 It has been suggested that liver biospy or bone marrow examination can provide a positive diagnosis in several such patients.  However, in situations where nonpulmonary organ involvment is not overt, such procedures may not be well accepted by patients. Since almost all these patients have obvious chest radiographic abnormalities, lung biopsy is theoretically the best modality to confirm diagnosis. Given the ease and low mobidity associated with fibreoptic bronchoscopic procedures, a bronchoscopic lung biopsy appears to be a better option than an open surgical or a thoracoscopic lung biopsy. A definite diagnosis made in a timely fashion is of utmost importance in instituting early treatment and preventing further dissemination of disease and reducing morbidity and mortality. It is well known that delay in administration of appropriate therapy is one of the most important factors influencing mortality in these patients.  We report the utility of bronchoscopic lung biopsy in making a prompt diagnosis of disease in these patients.
| Patients and Methods|| |
We undertook a retrospective review of records of patients of miliary tuberculosis undergoing fibreoptic bronchoscopy at our institute over a fouryear period. Patients were diagnosed as having miliary tuberculosis if they had (a) fever and other constitutional symptoms (with or without respiratory symptoms), (b) miliary mottling in lung fields on standard chest radiographs and/or high resolution computed tomographic scans, and (c) favorable clinical and radiological response to standard four-drug antitubercular treatment. Sputum smear was negative for acid-fast bacilli in all patients on at least three occassions. Patients were not routinely screened for presence of human immunodeficiency virus antibodies.
Fiberoptic bronchoscopy was carried out on routine outpatient basis in all patients using Olympus 1T20 bronchoscope through the nasal route with the patient lying supine. Informed consent was obtained from each patient immediately prior to the procedure. Preparation for the procedure included premedication with atropine and promethazine, followed by oral nebulization with 4% lignocaine. Sedation was not routinely employed. Additional lignocaine was instilled in measured doses through the bronchoscope during the procedure as required. After examination of endobronchial anatomy, bronchial washings and bronchoscopic lung biopsy were sequentially performed. Bronchial washings were typically obtained from the right middle lobe by injecting 20 ml of isotonic saline through the bronchoscope into the affected segment, followed by immediate suction. The procedure was repeated till at least 20 ml material was collected. The bronchial wash material thus obtained was concentrated and subjected to Ziehl Neelson staining for acid-fast bacilli as well as culture on Lowenstein Jenson slopes for six weeks. Bronchoscopic lung biopsies were taken from right lower lobe segments using Olympus biopsy forceps. Fluoroscopic guidance was not used in any procedure. Two to five specimens were obtained in each patient; these were fixed in formalin, embedded in paraffin and sections examined microscopically after Hematoxylin-eosin and Zeihl-Neelson staining. Biopsy specimens were not cultured for mycobacteria.
Based on the results of bronchoscopic examinations, a patient was diagnosed as having tuberculosis if bronchial wash smears were positive for acid-fast bacilli or if mycobacteria were isolated from these specimens on culture, or if bronchoscopic lung biopsy revealed presence of caseating granulomas or acid-fast bacilli.
| Results|| |
Thirty one patients of miliary tuberculosis underwent fibreoptic bronchoscopy during the study period. There were 19 men (mean age 44.1 ± 13.1 years) and 12 women (mean age 43.9 ± 14.5 years). No endobronchial abnormality was noted in any patient. Bronchoscopic lung biopsy yielded adeqaute specimen in all but one patient. Granulomatous inflammation with caseation was noted in 21 (67.7%) patients on histopathological evaluation of bronchoscopic lung biopsy specimens [Figure 1]; of them, acid-fast bacilli were demonstrated in only one patient. One patient (3.2%) had normal alveolar architecture. In the other eight patients (25.8%), nonspecific pulmonary interstitial inflammation and/or mild fibrosis were seen. These patients received empirical antitubercular treatment and subsequently responded well to therapy. Bronchial wash specimens showed acid-fast bacilli in only in one patient; this patient also had granulomatous inflammation on lung biopsy. None of the bronchial wash specimens grew mycobacteria on culture. All patients tolerated bronchoscopy well and there were no procedure-related complications.
| Discussion|| |
Bronchoscopic lung biopsy is now the preferred investigation in any diagnostic algorithm of a diffuse lung disease. We already have extensive experience in the procedure and have found it be an useful tool in diagnosing a variety of diseases like interstitial pulmonary fibrosis, sarcoidosis, malignancy and tuberculosis.  This procedure was first used to diagnose miliary tuberculosis nearly three decades ago by demonstrating acid-fast bacilli in a single patient.  Since then, several investigators have emphasised the utility of this procedure in establishing the diagnosis of miliary tuberculosis. In general, the yield of histological examination of transbronchial lung biopsy specimen has ranged between 60-80% of sputum smear negative patients of miliary tuberculosis in almost all reports. ,,,,,, The reasons for this high yield appear obvious. Miliary tuberculosis involves the lung diffusely, and therefore there is a good chance that representative tissue can be obtained even with a blind procedure. Bronchoscopic lung biopsy is also a safe procedure with a low incidence of complications such as airway bleeding and pneumothorax, even when the procedure is carried out without flouroscopic guidance. We routinely perform bronchoscopic lung biopsy without fluoroscopic guidance, and none of our patients had any such complication. 
Our diagnosis of miliary tuberculosis was based primarily on identification of typical necrotizing granulomatous inflammation on histopathological examination of lung biopsy specimens. Acid-fast bacilli could be demonstrated in the granulomata of only one patient. It has been previously documented that mycobacteria are infrequently demonstrated in granuloma of patients with miliary tuberculosis, both in lung tissue and in other specimens (such as bone marrow, liver, lymph nodes, etc.).  Our microbiological yield on bronchial wash specimens was also rather low, and is similar to previous experience. ,, This could be related to two factors. Firstly, there is predominant interstitial involvement in lungs affected by miliary tuberculosis, with very little shedding of mycobacteria into the alveolar spaces. It is therefore logical that the yield of any specimen that predominantly samples the alveolar spaces and airways would be low. This is also the explanation of the low yield of sputum examination in these patients. Secondly, lignocaine used for topical anesthesia during and before the procedure is known to have bacteriostatic activity, and may adversely affect growth of mycobacteria on culture media. 
We conclude that bronchoscopic lung biopsy is a safe procedure and an effective method of establishing diagnosis of miliary tubrculosis. Granulomatous inflammation can be well demonstrated in lung biopsy specimens in a majority of patients with this disease, and identification of acid-fast bacilli in these specimens need not be a prerequisite for making a positive diagnosis. Bronchial wash specimens do not provide significant additional information in this regard.
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