|Year : 2012 | Volume
| Issue : 1 | Page : 43-46
A prospective study to evaluate the utility of bronchoalveolar lavage by fiberoptic bronchoscopy in sputum smear negative patients with high suspicion of pulmonary tuberculosis
Ritesh Kamal1, Rakesh Sharma2, Tushar Sahasrabuddhe1, Sanantha K Dash1, Mujeeb Showkat1, Nitin S Gaikwad1
1 Department of Pulmonary Medicine, Dr. D. Y. Patil Medical College, Pune, India
2 Department of Anaesthesiology, Indraprastha Apollo Hospital, New Delhi, India
|Date of Web Publication||20-Jun-2012|
Raj Niwas, 1-A, Swatanter Nagar, Narela, Delhi - 110040
Source of Support: None, Conflict of Interest: None
Aim: To evaluate the utility of bronchoalveolar lavage (BAL) by flexible fiberoptic bronchoscopy (FOB) in sputum smear negative patients with clinical and radiological characteristics of pulmonary tuberculosis (PTB). Materials and Methods: This prospective study was carried out in 30 sputum smear negative patients of age group 20 to 70 years, who were highly suspicious for PTB by clinical and radiographic criteria. All patients were subjected to sputum culture, BAL stains and cultures, and cytopathology. Patients with moderate to massive pleural effusion, obvious accessible lymph node, history of antitubercular therapy (ATT), and contraindication to FOB were excluded. Results: Sputum culture for acid fast bacilli (AFB) was positive in four (12%) patients, BAL fluid was positive for Ziehl-Neelsen (ZN) stain in nine (27%) patients, including four sputum culture patients, while BAL culture for AFB on Lowenstein-Jensen (LJ) medium was positive in 18 (60%), including 9 BAL fluid ZN stain positive patients. Six (20%) patients had growth on pyogenic culture, while two (7%) patients had malignant cell on cytological examination of BAL fluid. Remaining four (13%) patients were empirically started on ATT. They had complete response to ATT at 2 months and were retrospectively diagnosed with pulmonary tuberculosis (PTB). All the bacteriologically confirmed PTB patients were given ATT for 6 months and all patients had complete response. Conclusion: We concluded that FOB guided BAL is extremely useful for establishing diagnosis of PTB or other pulmonary diseases in sputum smear negative patients, who have high suspicion for PTB by clinical and radiographic criteria.
Keywords: Bronchoalveolar lavage, fiberoptic bronchoscopy, pulmonary tuberculosis
|How to cite this article:|
Kamal R, Sharma R, Sahasrabuddhe T, Dash SK, Showkat M, Gaikwad NS. A prospective study to evaluate the utility of bronchoalveolar lavage by fiberoptic bronchoscopy in sputum smear negative patients with high suspicion of pulmonary tuberculosis. Med J DY Patil Univ 2012;5:43-6
|How to cite this URL:|
Kamal R, Sharma R, Sahasrabuddhe T, Dash SK, Showkat M, Gaikwad NS. A prospective study to evaluate the utility of bronchoalveolar lavage by fiberoptic bronchoscopy in sputum smear negative patients with high suspicion of pulmonary tuberculosis. Med J DY Patil Univ [serial online] 2012 [cited 2019 Nov 19];5:43-6. Available from: http://www.mjdrdypu.org/text.asp?2012/5/1/43/97511
| Introduction|| |
Pulmonary Tuberculosis (PTB) is a major health problem in developing countries. Sputum-examination for AFB is a reliable and inexpensive diagnostic method,  but in some patients with a very suggestive clinical course and chest radiograph, AFB cannot be demonstrated in the sputum. , The Bactec system enhances the isolation and shortens the detection time, but it requires expensive instrumentation and disposal of radioactive waste place severe restrictions on its use.  Patients clinically suspected to have PTB, with no laboratory confirmatory evidence present a difficult diagnostic and therapeutic problem. The clinician is faced with the decision of initiating empirical antitubercular therapy (ATT) or employing more invasive techniques seeking to document PTB and to exclude other disease processes.  In view of above scenario, it is very important to establish the diagnosis of PTB as well as other pulmonary pathologies.
| Materials and Methods|| |
This prospective study was conducted in a tertiary care teaching hospital from April 2007 to March 2010. The study involved 30 consecutive patients who had clinical features and chest radiography finding suggestive for PTB. Selected patients had three consecutive early morning sputum smears negative for AFB by Ziehl-Neelsen (ZN) stain and no response to usual antibiotics used for community acquired pneumonia for 2 weeks. Patients with following characteristics were excluded: moderate to massive pleural effusion, obvious accessible lymph node involvement, history of ATT, and contraindication to fiberoptic bronchoscopy (FOB). Sputum samples of all patients were tested for stains (Gram stain, fungal smear) and culture (pyogenic, fungal, and mycobacterial).
We used flexible fiberoptic bronchoscope. FOB was performed through transnasal route in supine position with continuous monitoring of blood pressure, electrocardiogram, and pulse oximetry. Oxygen was administered to maintain oxygen saturation >90%. Adequate local anesthesia was obtained with lignocaine. Stepwise examination was done starting from glottis, trachea, carina, right main bronchus, lobar bronchi, segmental bronchi, and then repeated on the left side. BAL was done with 50 ml of normal saline at the end of procedure in the region corresponding to lesion on chest radiograph. Bronchoscope was removed smoothly, while observing for any trauma. Patients were kept nil by mouth for 2 more hours and observed for development of any potential complication. BAL samples were sent for stains (Gram stain, ZN stain, Fungal smear), culture (Pyogenic, mycobacterial, and fungal), and cytopathology. A final diagnosis of PTB was based on a positive sputum mycobacterial culture (LJ media), positive BAL AFB smear, or BAL mycobacterial culture (LJ medium), or a clinical response to TB treatment at the 2 month follow-up visit.
| Results|| |
All patients with age from 20 to 70 years were included with 21 males and 9 females [Table 1].
Most common symptom was cough (86%) [Table 2]. Duration of symptoms in all these patients was about 3−4 weeks. All patients received antibiotics for 14 days before diagnostic bronchoscopy, 22 patients received amoxicillin and 06 patients received cephalosporins, and remaining 02 patients received macrolides.
The most common site of affection on chest radiograph was upper lobes [Table 3].
During bronchoscopy, following abnormalities were noted [Table 4].
Sputum samples of all patients were cultured on LJ medium. Four patients (20%) showed growth on LJ medium. ZN staining of BAL sample was positive in nine (30%) patients. In 18 patients (60%), BAL sample showed growth of mycobacteria on LJ medium. So, finally, as shown in [Figure 1] and [Table 5], 18 patients (60%) were bacteriologically confirmed to have pulmonary TB. Four patients (13%) were retrospectively confirmed to have PTB on the basis of their response to ATT. Six patients (20%) were having pneumonia and eventually responded to extended courses of antibiotics. All these six patients had positive growth on pyogenic culture of bronchial aspirate. Two patients (7%) were later on diagnosed with malignancy. Both of these patients were male more than 60 years of age.
|Figure 1: 1- Patients with bacteriological confi rmed PTB, 2- Patients with retrospective diagnosis of PTB, 3- Patients with nonresolving pneumonia, 4- Patients with pulmonary malignancy|
Click here to view
Most common complications during and after FOB were tachycardia (80%), sore throat (17%), and fever (17%). Three patients (10%) complaint of mild hemoptysis and two patients (7%) were hypoxic after FOB, requiring oxygen supplementation.
| Discussion|| |
Tuberculosis (TB) is among the leading causes of morbidity and mortality worldwide.  TB causes about two million deaths per year, majority of which occur in underdeveloped countries.  Microscopy for the identification of AFB is rapid and inexpensive,  but AFB are undetectable in sputum smear in a significant number of patients with active PTB. ,
Sputum microscopy continues to be the best tool for detection of infectious PTB  in patients with a compatible clinical picture; however, sputum smears do not reveal AFB in all patients.  Patients who are sputum smear negative but with clinical and radiographic features of PTB, are a challenge for the physician. If untreated, about 3/4 th of these patients develop active PTB in 5 years.  Early diagnosis and treatment, to make the TB patient noninfectious, is the main approach for control of TB. Despite new diagnostic techniques, posterior-anterior chest radiograph remains the primary laboratory test for suggesting diagnosis of PTB.  Microbiological methods like ZN staining and mycobacterial culture on LJ medium are gold standard for diagnosis of PTB but many times their results are falsely negative.
Since the introduction of fiberoptic bronchoscope by Ikeda in 1968, a number of studies have shown usefulness of FOB in undiagnosed pulmonary pathologies.  Among various bronchoscopic specimens, BAL is considered best for diagnosis of PTB.  We evaluated utility of FOB in 30 patients, who have clinical and radiographic features of PTB but were negative on sputum ZN staining. Cough, fever, anorexia, and weight loss were the most common symptoms, as reported in previous studies. 
The most characteristic radiological feature in primary PTB is lymphadenopathy.  Other radiographic features are patchy and poorly defined consolidation in the apical and posterior segments of the upper lobes and in the superior segment of the lower lobe, miliary TB, and pleural effusion.  Radiographic features of post primary PTB are cavitation, tuberculoma, bronchial stenosis, bronchiectasis, bronchopleural fistula, and pleural disease.  Most of the patients in our study had lesions involving the upper lobes.
All the patients had three negative early morning spot sputum ZN staining. Earlier studies have documented high incidence of false negative sputum ZN staining in PTB.  Sputum of 4 out of 30 patients of suspected PTB showed growth on LJ medium, so sensitivity of sputum culture was 13.3%. The most common bronchoscopic finding in this study was mucosal hyperemia and edema of the affected site (59%). Only nine patients were positive on the staining of BAL. So, the sensitivity of ZN staining of the BAL was 27% and it underscores the importance of AFB culture of BAL. BAL AFB culture was positive in 18 patients and all the patients were positive on BAL AFB staining and sputum AFB culture, so definitive diagnosis was established in 18 out of 22 patients with PTB. Chawala et al., were able to establish diagnosis of PTB in 45 out of 50 patients but they have also used bronchial biopsy and brush smear and 12 patients in their study were positive for AFB stain.  In another study of 30 patients, BAL culture yield was 73.3% for PTB. 
BAL fluid of six patients had growth on pyogenic culture and were diagnosed with non resolving pneumonia. These patients were given antibiotics for extended period and all had complete resolution of their symptoms and radiographic lesions. Two patients were diagnosed with malignancy on cytopathological examination of BAL and both of these patients were male more than 60 years of age. In a similar study by Rao et al. 5 out of 55 patients were diagnosed with bronchial carcinoma.  But still no diagnosis could be made in four patients by bronchoalveolar lavage (BAL). As these patients were having clinical and radiographic feature of PTB, we decided to give empirical ATT to these patients. All these patients had complete resolution of their symptoms and were retrospectively diagnosed with PTB. A final diagnosis of PTB was based on a positive sputum mycobacterial culture on LJ media, positive BAL AFB smear by ZN stain, or mycobacterial culture on LJ media, or a clinical response to ATT at the two month follow-up visit.
So, in this study out of 22 cases of PTB, 18 cases were diagnosed by bronchial aspirate cultures, earning sensitivity of 82% while sensitivity of staining of bronchial aspirate was only 41% and of sputum culture only 18%. In addition, BAL fluid culture and cytopathological examination were able to establish diagnosis in 86.6% of the patient and to diagnose other pulmonary diseases which can present like PTB. During and after FOB, Tachycardia was the most common complication followed by the fever and six patients had mild hemoptysis. Considering these complications, FOB and BAL are relatively safe invasive test used for diagnosis of PTB and other pathologies. To prevent cross-contamination, guidelines such as those issued by the American College of Chest Physicians and the American Association of Bronchology for infection control were followed. 
So, as shown in our study, microbiological culture of BAL obtained with FOB not only provides definitive diagnosis of PTB with higher sensitivity compared to sputum smear or sputum culture but also provides alternative diagnosis in sputum smear negative patients, thereby preventing unnecessary exposure to ATT.
The limitation in this study was that only ZN staining and AFB culture on LJ medium of sputum and BAL sample was performed and no other investigative method for diagnosis ofPTB. Therefore, no comparison with other methods was possible. Also countries with high prevalence of PTB also have limitation of resources. So, further research is required on the feasibility and cost-effectiveness of FOB for PTB diagnosis in resource-limited countries before it can be recommended as a useful tool.
| References|| |
|1.||Steingart KR, Ng V, Henry M, Hopewell PC, Ramsay A, Cunningham J, et al. Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: A systematic review. Lancet Infect Dis 2006;6:664-74. |
|2.||Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B. Paediatric tuberculosis. Lancet Infect Dis 2008;8:498-510. |
|3.||Daniel TM. The rapid diagnosis of tuberculosis: A selective review. J Lab Clin Med 1990;116:277-82. |
|4.||Luquin M, Gamboa F, Barcelo MG, Manterola JM, Matas L, Gimenez M, et al. Comparison of a biphasic non-radiometric system with Lowenstein-Jensen and Bactec-460 system for recovery of mycobacteria from clinical specimens. Tuber Lung Dis 1996;77:449-53. |
|5.||Hong King Chest Service / Tuberculosis Research Centre, Madras/ British Medical Research Council. A controlled trial of 2 months, 3 months, and 12 -month regimens of chemotherapy for sputum smear negative pulmonary tuberculosis: Results at 60 months. Am Rev Respir Dis 1984;130:23-8. |
|6.||Dye C. Global epidemiology of tuberculosis. Lancet 2006;367:938-40. |
|7.||Maher D, Raviglione M. Global epidemiology of tuberculosis. Clin Chest Med 2005;26:167-82. |
|8.||TB India. WHO Stop TB Strategy. RNTCP Status Report, March. Central TB Division, Directorate General of Health Services, New Delhi; 2008. p. 14. |
|9.||Kim TC, Blackman RS, Heatwole KM, Rochester DF. Acid fast bacilli in sputum smears of patients with pulmonary tuberculosis: Prevalence and significance of negative smears pretreatment and positive smears post treatment. Am Rev Respir Dis 1984;29:264-8. |
|10.||Choyke PL, Sostman HD, Curtis AM, Ravin CE, Chen JT, Godwin JD, et al. Adult-onset pulmonary tuberculosis. Radiology 1983;148:357-62. |
|11.||Cordani S, Manna A, Vignali M, Tascini C. Bronchoalveolar lavage as a diagnostic tool in patients with haematological malignancies and pneumonia. Infez Med 2008;16:209-13. |
|12.||Venkateshiah SB, Mehta AC. Role of flexible brochoscopy in the diagnosis of pulmonary tuberculosis in immunocompetent individuals. J Bronchol 2003;10:300-6. |
|13.||Miller WT, MacGregor RR. Tuberculosis: Frequency of unusual radiographic findings. AJR Am J Roentgenol 1978;130:867-75. |
|14.||Andreu J, Caceres J, Pallisa E, Martinez-Rodriguez M. Radiological manifestations of pulmonary tuberculosis. Eur J Radiol 2004;51:139-49. |
|15.||Laifangbam S, Singh HL, Singh NB, Devi KM, Singh NT. A comparative study of fluorescent microscopy with Ziehl-Neelsen staining and culture for the diagnosis of pulmonary tuberculosis. Kathmandu Univ Med J (KUMJ) 2009;7:226-30. |
|16.||Chawla R, Pant K, Jaggi OP, Chandrashekhar S, Thukral SS. Fibreoptic bronchoscopy in smear-negative pulmonary tuberculosis. Eur Respir J 1988;1:804-6. |
|17.||Caminero Luna JA, Rodriguez de Castro F, Campos-Herrero I, Díaz Lopez F, Pavon Monzo JM, Acosta Fernandez O, et al. The efficacy of bronchoalveolar lavage in the diagnosis of pulmonary tuberculosis. Arch Bronconeumol 1994;30:236-9. |
|18.||Rao S. Significance of bronchial washings smear negativity in 'suspect' pulmonary tuberculosis. Trop Doct 1993;23:170-1. |
|19.||Mehta AC, Prakash UB, Garland R, Haponik E, Moses L, Schaffner W, et al. American College of Chest Physicians and American Association for Bronchology [corrected] consensus statement: Prevention of flexible bronchoscopy-associated infection. Chest 2005;128:1742-55. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]