Usefulness of Induced Sputum and Fibreoptic Bronchoscopy Specimens in the Diagnosis of Pulmonary Tuberculosis

Transcription

1 The Journal of International Medical Research 2005; 33: Usefulness of Induced Sputum and Fibreoptic Bronchoscopy Specimens in the Diagnosis of Pulmonary Tuberculosis L SAGLAM 1, M AKGUN 1 AND E AKTAS 2 1 Department of Chest Diseases and 2 Department of Microbiology, Faculty of Medicine, Atatürk University, Erzurum, Turkey We investigated the diagnostic value of induced sputum (IS) and bronchial lavage (BL) specimens in patients with suspected pulmonary tuberculosis who had negative spontaneous sputum specimens or who were unable to produce sputum spontaneously. IS specimens and BL specimens obtained using flexible fibreoptic bronchoscopy from 55 patients were evaluated for the presence of acid-fast bacilli (AFB) and cultured for Mycobacterium tuberculosis. Positive results were found with IS smear in 23 patients, BL smear in 26 patients, and IS or BL culture in 42 patients. Culture of BL specimens had a higher sensitivity than IS or BL smears or culture of IS specimens. The highest sensitivity rate was obtained with a positive BL or IS culture (86%). For early diagnosis (a positive IS or BL smear), the sensitivity was 57%. IS has a higher sensitivity rate than spontaneous sputum for the detection of tuberculosis, and fibreoptic bronchoscopy is useful for the early diagnosis of tuberculosis when AFB are not detected in spontaneous or induced sputum specimens. KEY WORDS: TUBERCULOSIS; INDUCED SPUTUM; BRONCHOSCOPY Introduction Tuberculosis is one of the most important health problems worldwide. 1 The World Health Organization (WHO) recommends bacteriological confirmation of pulmonary tuberculosis (PT) by the detection of acid-fast bacilli (AFB) in respiratory specimens. 2 Gastric lavage specimens (particularly in children), induced sputum (IS) specimens or bronchial lavage (BL) specimens obtained using fibreoptic bronchoscopy may provide confirmation of the diagnosis in patients with suspected PT who do not produce sputum or who have a negative AFB smear from spontaneous sputum (SS). IS testing is safe and effective. Bronchoscopy is more invasive and expensive than IS, but can provide specimens from specific sites in the lung. We aimed to investigate the diagnostic value of IS and BL specimens in patients suspected to have PT. Patients and methods The study was conducted between January 2001 and June 2003 in Atatürk University Research Hospital Department of Pulmonary Diseases in Erzurum, Turkey. 260

2 PATIENTS Patients with respiratory symptoms and radiographic findings suspicious for PT were evaluated for enrolment in the study. SS specimens were collected for 3 consecutive days; patients whose smears were positive for AFB were excluded. Patients who had a SS smear negative for AFB or who were unable to produce sputum spontaneously were evaluated prospectively. All patients who participated in the study gave informed consent and the study was approved by our local ethics committee. Patients with severe asthma, haemoptysis or chronic obstructive pulmonary disease were not included in the study. DIAGNOSTIC PROCEDURES Tuberculin skin and human immunodeficiency virus (HIV) tests were performed in all patients. Sputum was induced using 3% hypertonic saline solution delivered by ultrasonic nebulizer in a special room, and specimens collected. Flexible bronchoscopy and BL using 50 ml of lavage fluid were carried out h later; these procedures were all undertaken by the same physician (a specialist in pulmonary diseases) in our clinic. A maximum 100 mg of lidocaine (Xylocaine, AstraZeneca, Södertalje, Sweden) 2% spray was used as pre-medication, with a maximum 80 mg of lidocaine (4 ml of 2% spray) being used during the bronchoscopy. The IS and BL smears were examined for AFB using the Ziehl-Neelsen method, and specimens were cultured for up to 8 weeks in Lowenstein-Jensen medium for Mycobacterium tuberculosis. DATA ANALYSIS The sensitivity, specificity and positive and negative predictive values of IS and BL smears and cultures were calculated. Results A total of 55 patients (28 males and 27 females) were included in the study. The mean (± SD) age of the patients was 35.8 ± 17 years (range years). Both sputum induction and fibreoptic bronchoscopy were well tolerated in all patients. The results of the smears for AFB and cultures for M. tuberculosis are shown in Tables 1 and 2 for IS and BL specimens, respectively, and are compared in Table 3. The sensitivities, specificities and negative and positive predictive values of AFB smears and mycobacterial cultures of the IS and BL specimens are shown in Table 4. Pulmonary tuberculosis was diagnosed in 42 patients microbiologically (i.e. a positive IS and/or BL culture). Seven patients were diagnosed with pulmonary tuberculosis on clinical and radiological grounds; three of these cases had miliary tuberculosis. Nontuberculosis diseases were diagnosed in the other six patients (pneumonia in two, TABLE 1: Results of smears for acid-fast bacilli (AFB) and cultures for Mycobacterium tuberculosis in induced sputum specimens obtained from 55 patients with suspected pulmonary tuberculosis Smear for AFB Culture for M. tuberculosis Positive Negative Positive 22 9 Negative

3 TABLE 2: Results of smears for acid-fast bacilli (AFB) and cultures for Mycobacterium tuberculosis in bronchial lavage specimens obtained from 55 patients with suspected pulmonary tuberculosis Smear for AFB Culture for M. tuberculosis Positive Negative Positive 26 7 Negative 0 16 TABLE 3: Comparison of results of smears for acid-fast bacilli (AFB) and cultures for Mycobacterium tuberculosis in induced sputum and bronchial lavage specimens obtained from 49 patients with suspected pulmonary tuberculosis (results for six additional patients diagnosed with non-tuberculosis diseases are not included) Smear Induced sputum results Culture Bronchial lavage results + + Smear Culture TABLE 4: Sensitivity, specificity and positive and negative predictive values of induced sputum (IS) and bronchial lavage (BL) smear and culture results for the diagnosis of tuberculosis in this study Positive Negative predictive predictive Sensitivity Specificity value value Effectiveness Result n (%) (%) (%) (%) (%) Positive IS smear Positive IS culture Positive BL smear Positive BL culture Positive IS and/or BL culture Positive IS and/or BL smear

4 bronchiectasis in three, and bronchogenic carcinoma in one). The test for HIV was negative in all patients, and the tuberculin skin test was positive in 35 patients. Discussion When pulmonary tuberculosis is suspected, the first step is to investigate whether AFB are present in the sputum; this is particularly useful for making a prompt diagnosis of tuberculosis. Culture of specimens to demonstrate the presence of M. tuberculosis is also important but takes approximately 2 6 weeks, whereas an early diagnosis allows treatment to be started sooner. When SS is not available, sputum induction or fibreoptic flexible bronchoscopy may produce specimens for diagnostic use. In this study we investigated the value of IS and bronchoscopy specimens in the early diagnosis of tuberculosis. The results of our study and other studies are compared in Table 5. Only three studies comparing IS and bronchoscopic results have been reported; 3 5 other published studies deal with either IS or bronchoscopic examination. Since the HIV test was negative in all of our cases, only the findings in HIV-negative patients in the study of Conde et al. 4 were used for comparison. The sensitivities for AFB in IS and BL smears obtained in our study were higher than those in previous studies, except those reported by McWilliams et al., 5 in which the AFB sensitivity was found to be increased in repeated IS specimens. McWilliams et al. used both the fluorochrome and Ziehl-Neelsen staining methods for AFB. 5 For both IS and bronchoscopic specimens, the diagnostic rates using AFB smears were TABLE 5: Comparison of the diagnostic sensitivity rates using induced sputum (IS) or bronchoscopic (BS) specimens in studies by ourselves and others IS smear IS culture BS smear BS culture Reference (%) (%) (%) (%) Andersen et al Conde et al McWilliams et al Present study Willcox et al (39/89) 67 (60/89) Chawla et al (36/50) 90 (45/50) Wongthim et al (38/65) 76 Fujii et al (18/45) Charoenratanakul et al (10/40) 33 (13/40) Parry et al (18/73) 55 (40/73) Merrick et al (6/24) Li et al (558/1648) Hartung et al (15/36) 263

5 low, but were higher for mycobacterial cultures. Differences in the results from the various studies may be related to differences in the procedures used, co-operation of the patient, experience of the physician, dose of lignocaine used, transportation of specimens to the laboratory and levels of laboratory specialization. In our study, the dose of lignocaine used for pre-medication and during bronchoscopy was as low as possible. The amount of the fluid used for BL may also affect the results: McWilliams et al. 5 used 40 ml and Andersen et al. 3 used ml, whereas we used 50 ml. The use of BL or bronchoalveolar lavage (BAL) may also have an effect: most of the reported studies, including ours, used BL, but Conde et al. 4 used BAL. Differences in results may also be related to differences in patient populations and the severity and spread of the disease. Studies of IS have shown that the rate of diagnosis was increased using IS specimens in patients with suspected tuberculosis who had negative SS smears. In a study by Parry et al., 6 the early diagnostic rate using IS smears was 25%, and the late diagnostic rate using IS cultures was 41% (Table 5). Merrick et al. 7 claimed that IS specimens were costly to produce and had no advantage over SS specimens with respect to diagnostic value. Li et al. 8 reported a diagnostic rate of 34% for IS smears in a large patient population. Studies of bronchoscopy have shown that the diagnosis of tuberculosis was increased in cases with negative SS smears using flexible fibreoptic bronchoscopy. In the study by Willcox et al., 10 an early diagnosis was made in 44% of patients using brushing and biopsy; this value increased to 67% using mycobacterial culture. Fujii et al. 13 found AFB in 40% of their bronchoscopy specimens, and Charoenratanakul et al. 14 made an early diagnosis using bronchoscopy in 25% of their patients. In the study of Chawla et al. 11 the early diagnostic rate was 72%, and this increased to 90% using culture; the corresponding rates reported by Wongthim et al. 12 were 58% and 76%. We conclude that both IS and BL specimens were valuable for the diagnosis of tuberculosis in patients with a SS smear negative for AFB or who were unable to produce sputum spontaneously. Both procedures, but particularly BL, are costly, invasive, difficult to perform and time-consuming, and carry a high risk of contamination. We suggest IS should be performed in patients with negative SS smears. If three consecutive IS smears are negative for AFB, bronchoscopy should then be performed. Conflicts of interest No conflicts of interest were declared in relation to this article. Received for publication 7 May 2004 Accepted subject to revision 24 May 2004 Revised accepted 27 May 2004 Copyright 2005 Cambridge Medical Publications References 1 Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC: Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999; 282: World Health Organization: Treatment of Tuberculosis: Guidelines for National Programmes, 3rd edn. Switzerland, Geneva: WHO, Andersen C, Inhaber N, Menzies D: Comparison of sputum induction with fiberoptic bronchoscopy in the diagnoses of tuberculosis. Am J Respir Crit Care Med 1995; 152:

6 4 Conde MB, Soares SL, Mello FC, Rezende VM, Almeida LL, Reingold AL, et al: Comparison of sputum induction with fiberoptic bronchoscopy in the diagnosis of tuberculosis: experience at an acquired immune deficiency syndrome reference center in Rio de Janeiro, Brazil. Am J Respir Crit Care Med 2000; 162: McWilliams T, Wells AU, Harrison AC, Lindstrom S, Cameron RJ, Foskin E. Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis. Thorax 2002; 57: Parry CM, Kamoto O, Harries AD, Wirima JJ, Nyirenda CM, Nyangulu DS, et al: The use of sputum induction for establishing a diagnosis in patients with suspected pulmonary tuberculosis in Malawi. Tuber Lung Dis 1995; 76: Merrick ST, Sepkowitz KA, Walsh J, Damson L, McKinley P, Jacobs JL. Comparison of induced versus expectorated sputum for diagnosis of pulmonary tuberculosis by acid-fast smear. Am J Infect Control 1997; 25: Li LM, Bai LQ, Yang HL, Xiao CF, Tang RY, Chen YF, et al: Sputum induction to improve the diagnostic yield in patients with suspected pulmonary tuberculosis. Int J Tuberc Lung Dis 1999; 3: Hartung TK, Maulu A, Nash J, Fredlund VG: Suspected pulmonary tuberculosis in rural South Africa sputum induction as a simple diagnostic tool? S Afr Med J 2002; 92: Willcox PA, Benatar SR, Potgieter PD: Use of the flexible fiberoptic bronchoscope in diagnosis of sputum-negative pulmonary tuberculosis. Thorax 1982; 37: Chawla R, Pant K, Jaggi OP, Chandrashekhar S, Thukral SS: Fibreoptic bronchoscopy in smearnegative pulmonary tuberculosis. Eur Respir J 1998; 1: Wongthim S, Udompanich V, Limthongkul S, Charoenlap P, Nuchprayoon C: Fiberoptic bronchoscopy in diagnosis of patients with suspected active pulmonary tuberculosis. J Med Assoc Thai 1989; 72: Fujii H, Ishihara J, Fukaura A, Kashima N, Tazawa H, Nakajima H, et al: Early diagnosis of tuberculosis by fibreoptic bronchoscopy. Tuber Lung Dis 1992; 73: Charoenratanakul S, Dejsomritrutai W, Chaiprasert A. Diagnostic role of fiberoptic bronchoscopy in suspected smear negative pulmonary tuberculosis. Respir Med 1995; 89: Address for correspondence L Saglam Department of Chest Diseases, Faculty of Medicine, Atatürk University, Erzurum 25100, Turkey. saglamleyla@hotmail.com 265