Yield of Bronchoscopy for the Diagnosis of Tuberculosis in Patients with Human Immunodeficiency Virus Infection* Daniel J Kennedy, M.D.; t William P. l£wis, Ph.D.;+ and Peter F. Barnes, M.D.t
The efficacy of bronchoscopy for the diagnosis of tuberculosis in patients infected with human immunode6ciency virus (UIV) has not been systematically evaluated. We therefore compared the diagnostic yield of bronchoscopy in 67 UIV-infected and 45 non-UIV-infected patients with culture-proven pulmonary tuberculosis. In all cases, acidfast smears of sputum were negative or not obtained prior to bronchoscopy. Prebronchoscopic sputum culture yielded Mycobacterium tuberculosis in 34 (89 percent) of 38 UIVinfected patients and 26 (93 percent) of 28 non-UIV-infected patients from whom specimens were obtained. Bronchoscopy provided an early diagnosis of tuberculosis (positive acid-fast smear or granulomata on biopsy) in 23 (34 percent) of the UIV-infected patients and 20 (44 percent) of the patients without UIV infection. The sensitivities of the acid-
fast smear and of mycobacterial culture of bronchoscopic specimens and postbronchoscopic sputum were similar in infection. In "IV-infected patients with or without patients, granulomatous inflammation was noted on transbronchial biopsy in II (19 percent) of 59 patients with HIV infection, compared to 16 (43 percent) of37 patients without HIV infection (p=O.OI). Nevertheless, transbronchial biopsy provided the exclusive means for an early diagnosis of tuberculosis in six (10 percent) of 59 HIV-infected patients. We conclude that the yield of bronchoscopy for the diagnosis of pulmonary tuberculosis in "IV-infected patients is similar to that in patients without "IV infection, and that transbronchial biopsy provides incremental diagnostic information not available from evaluation of sputum or bronchoalveolar lavage fluid. (Chest 1992; 102:1040-44)
Tuberculosis remains the leading cause of mortality from any infectious human pathogen, resulting in an estimated 3 million deaths annually worldwide.' In the United States, the number of cases of tuberculosis reported annually to the Centers for Disease Control rose by 3 percent in 1986, by 5 percent in 1989, and by a provisional 9 percent in 199()2·3 (Richard O'Brien, M.D., Centers for Disease Control, oral communication May 13, 1991). These increases are largely due to the extraordinary susceptibility of patients with human immunodeficiency virus (HIV) infection to tuberculosis. 2 •3 Tuberculosis is an important complication of HIV infection because it is transmissible by the respiratory route, is readily treatable, and is potentially preventable through chemoprophylaxis. Pulmonary disease is the most common manifestation of tuberculosis in HIV-infected patients, and a rapid presumptive diagnosis is usually based on identification of acid-fast organisms in sputum. Unfortunately, sputum smears for acid-fast bacilli are often negative in HIV-infected patients with tuberculosis, as is the case in those without "IV infection. 4 -7 In HIV-infected patients
with pulmonary disease of undetermined etiolo~, bronchoscopy is comlnonly performed for diagnostic purposes. Although bronchoscopy is a valuable procedure for the diagnosis of tuberculosis in patients without "IV infection/~-ll limited data on the results of bronchoscopy in 21 HIV-infected patients \\,ith tuberculosis su~ested that the diagnostic yield \vas relatively low. '2 To systematically evaluate the efficacy of bronchoscopy for the diagnosis of tuberculosis in HIV-infected patients, \\'e compared the results of bronchoscopy in HIV-infected and non-HIV-infected patients \\'ith pulmonary tuberculosis.
*From the Departments of Medicine and Patholo~, University of Southern California School of Medicine, Los Angeles. Computational assistance was provided by the National Institutes of Health, National Center for Research Resources, CCRC MOl RR-43 CLINFO project. tDepartment of Medicine. :t:Department of Patholo~. Manuscript received October 4; revision accepted January 2, 1992. Reprint requests: Dr. Barnes, HMR 904, USC School of Aledicine, 2025 Zonal Avenue, ws Angeles 90033
1040
"IV
MATERIALS AND METII()DS
Patients \Ve reviewed the records of the Inycohacteriolo~'ylahoratory and identified all patients cared for at the Los Angel(~s County-University of Southern California ~fedical Center frorll Jline I, 1986 through ~fay 31, 1990 in whonl pulrnonary specinlens yielded Alycobact(·rium tuberculosis. By nlatching this list against the record of all bronchoscopies perfi>rmed during this peri(KI, we identified 153 patients \"ith culture-proven pulmonary tuherculosis who under\\'ent bronchoscopy within 1 nlO of the date that a pulrnonary specimen yielding AI tuberculosi.r.; was ohtained. ~fedical records of 128 (84 percent) of these 153 patients wert" availahle for revit"w. In 112 of these 129 patients, acid-fast slnt"ars of spuhnll wen' negative or were not ohtained prior to hronchoscopy, and these 112 patients constitute the study population. Medical rer acid-fast smear and mycobacterial culture in 98 (88 percent) of the 112 patients, and transbronchial biopsies were obtained in 96 cases (86 percent). Transbronchial biopsy specimens were placed in a forrnaldehyde solution (10 percent Formalin) for histopathologic exarnination, and in physiologic saline fi)r mycobacterial studies. Sputum, bronchoalveolar lavage fluid, and transbronchial biopsy specilllens were deconhnninated with NaOn, and acid-fast stains were perforrned by the nlethod of Truant. t\.1ycobacteria were cultured and speciated by standard criteria. n \Ve considered bronchoscopy to be positive for the dia~nosis of tuberculosis if(l) any bronchos(.·opic specimen or postbronchoscopic sputUlll sample (obtained within 48 h after bronchos(.'()py) revealed acid-fast bacilli on Slllear or AI tuberculosis on culture, or (2) granulonlatous inflamlllation was noted on histopathologic examination of a transbronchial biopsy specimen, and culture of sputum or hronchoscopic specilnens yielded AI tuberculosis. A bronchoscopy was considered to ('()ntrihute to an early diagnosis of tuberculosis if any bronchoscopk specirncn or postbronchoscopic sputum sample revealed acid-fast hacilli on snlcar or if granulomatous inflarllrnation was noted in a transhronchial biopsy specimen.
Statistical Analysis Statistical analysis was perf()rrned using i-tests fi)r continuous variahles with a normal distribution and the \Vik'()xon rank-sum test for those that were not normally distrihuted. For cate~oric variables, the X;! test or Fisher's exact test \\'as used. RESULTS
Of the 67 patients with HIV infection, 65 (97 percent) \\'ere men; 26 (39 percent) \\'ere black, 22 (33 percent) \\'ere non-Hispanic white, and 19 (28 percent) \\'ere Hispanic. Of the 45 patients \vithout HIV infection, 33 (73 percent) \vere men; eight (18 percent) \vere black, seven (16 percent) were non-Hispanic white, 21 (47 percent) were Hispanic, ei~ht (18 percent) \\'ere Asian, and one (2 percent) was native Anlerican. The mean a~e (± SD) of patients \\rith HIV infection \\'as 36 ± 8 years, compared to 48 ± 17 years in those \\rithout HIV infection (p = 0.00(1). These
Table 1- Sensitivity of Sputum Culture and Bronchoscopic Tests in Patients with Pulmonary Tuberculosis*
Test Prebronchoseopic sputum Mycobacterial culture Bronchoalveolar lava~e Acid-fast smear ~I ycobacterial culture Transbronchial biopsy Acid-fast smear Mycobacterial culture Granulomatat Postbronchos
The efficacy of bronchoscopy for the diagnosis of tuberculosis in patients infected with human immunode6ciency virus (UIV) has not been systematically evaluated. We therefore compared the diagnostic yield of bronchoscopy in 67 UIV-infected and 45 non-UIV-infected patients with culture-proven pulmonary tuberculosis. In all cases, acidfast smears of sputum were negative or not obtained prior to bronchoscopy. Prebronchoscopic sputum culture yielded Mycobacterium tuberculosis in 34 (89 percent) of 38 UIVinfected patients and 26 (93 percent) of 28 non-UIV-infected patients from whom specimens were obtained. Bronchoscopy provided an early diagnosis of tuberculosis (positive acid-fast smear or granulomata on biopsy) in 23 (34 percent) of the UIV-infected patients and 20 (44 percent) of the patients without UIV infection. The sensitivities of the acid-
fast smear and of mycobacterial culture of bronchoscopic specimens and postbronchoscopic sputum were similar in infection. In "IV-infected patients with or without patients, granulomatous inflammation was noted on transbronchial biopsy in II (19 percent) of 59 patients with HIV infection, compared to 16 (43 percent) of37 patients without HIV infection (p=O.OI). Nevertheless, transbronchial biopsy provided the exclusive means for an early diagnosis of tuberculosis in six (10 percent) of 59 HIV-infected patients. We conclude that the yield of bronchoscopy for the diagnosis of pulmonary tuberculosis in "IV-infected patients is similar to that in patients without "IV infection, and that transbronchial biopsy provides incremental diagnostic information not available from evaluation of sputum or bronchoalveolar lavage fluid. (Chest 1992; 102:1040-44)
Tuberculosis remains the leading cause of mortality from any infectious human pathogen, resulting in an estimated 3 million deaths annually worldwide.' In the United States, the number of cases of tuberculosis reported annually to the Centers for Disease Control rose by 3 percent in 1986, by 5 percent in 1989, and by a provisional 9 percent in 199()2·3 (Richard O'Brien, M.D., Centers for Disease Control, oral communication May 13, 1991). These increases are largely due to the extraordinary susceptibility of patients with human immunodeficiency virus (HIV) infection to tuberculosis. 2 •3 Tuberculosis is an important complication of HIV infection because it is transmissible by the respiratory route, is readily treatable, and is potentially preventable through chemoprophylaxis. Pulmonary disease is the most common manifestation of tuberculosis in HIV-infected patients, and a rapid presumptive diagnosis is usually based on identification of acid-fast organisms in sputum. Unfortunately, sputum smears for acid-fast bacilli are often negative in HIV-infected patients with tuberculosis, as is the case in those without "IV infection. 4 -7 In HIV-infected patients
with pulmonary disease of undetermined etiolo~, bronchoscopy is comlnonly performed for diagnostic purposes. Although bronchoscopy is a valuable procedure for the diagnosis of tuberculosis in patients without "IV infection/~-ll limited data on the results of bronchoscopy in 21 HIV-infected patients \\,ith tuberculosis su~ested that the diagnostic yield \vas relatively low. '2 To systematically evaluate the efficacy of bronchoscopy for the diagnosis of tuberculosis in HIV-infected patients, \\'e compared the results of bronchoscopy in HIV-infected and non-HIV-infected patients \\'ith pulmonary tuberculosis.
*From the Departments of Medicine and Patholo~, University of Southern California School of Medicine, Los Angeles. Computational assistance was provided by the National Institutes of Health, National Center for Research Resources, CCRC MOl RR-43 CLINFO project. tDepartment of Medicine. :t:Department of Patholo~. Manuscript received October 4; revision accepted January 2, 1992. Reprint requests: Dr. Barnes, HMR 904, USC School of Aledicine, 2025 Zonal Avenue, ws Angeles 90033
1040
"IV
MATERIALS AND METII()DS
Patients \Ve reviewed the records of the Inycohacteriolo~'ylahoratory and identified all patients cared for at the Los Angel(~s County-University of Southern California ~fedical Center frorll Jline I, 1986 through ~fay 31, 1990 in whonl pulrnonary specinlens yielded Alycobact(·rium tuberculosis. By nlatching this list against the record of all bronchoscopies perfi>rmed during this peri(KI, we identified 153 patients \"ith culture-proven pulmonary tuherculosis who under\\'ent bronchoscopy within 1 nlO of the date that a pulrnonary specimen yielding AI tuberculosi.r.; was ohtained. ~fedical records of 128 (84 percent) of these 153 patients wert" availahle for revit"w. In 112 of these 129 patients, acid-fast slnt"ars of spuhnll wen' negative or were not ohtained prior to hronchoscopy, and these 112 patients constitute the study population. Medical rer acid-fast smear and mycobacterial culture in 98 (88 percent) of the 112 patients, and transbronchial biopsies were obtained in 96 cases (86 percent). Transbronchial biopsy specimens were placed in a forrnaldehyde solution (10 percent Formalin) for histopathologic exarnination, and in physiologic saline fi)r mycobacterial studies. Sputum, bronchoalveolar lavage fluid, and transbronchial biopsy specilllens were deconhnninated with NaOn, and acid-fast stains were perforrned by the nlethod of Truant. t\.1ycobacteria were cultured and speciated by standard criteria. n \Ve considered bronchoscopy to be positive for the dia~nosis of tuberculosis if(l) any bronchos(.·opic specimen or postbronchoscopic sputUlll sample (obtained within 48 h after bronchos(.'()py) revealed acid-fast bacilli on Slllear or AI tuberculosis on culture, or (2) granulonlatous inflamlllation was noted on histopathologic examination of a transbronchial biopsy specimen, and culture of sputum or hronchoscopic specilnens yielded AI tuberculosis. A bronchoscopy was considered to ('()ntrihute to an early diagnosis of tuberculosis if any bronchoscopk specirncn or postbronchoscopic sputum sample revealed acid-fast hacilli on snlcar or if granulomatous inflarllrnation was noted in a transhronchial biopsy specimen.
Statistical Analysis Statistical analysis was perf()rrned using i-tests fi)r continuous variahles with a normal distribution and the \Vik'()xon rank-sum test for those that were not normally distrihuted. For cate~oric variables, the X;! test or Fisher's exact test \\'as used. RESULTS
Of the 67 patients with HIV infection, 65 (97 percent) \\'ere men; 26 (39 percent) \\'ere black, 22 (33 percent) \\'ere non-Hispanic white, and 19 (28 percent) \\'ere Hispanic. Of the 45 patients \vithout HIV infection, 33 (73 percent) \vere men; eight (18 percent) \vere black, seven (16 percent) were non-Hispanic white, 21 (47 percent) were Hispanic, ei~ht (18 percent) \\'ere Asian, and one (2 percent) was native Anlerican. The mean a~e (± SD) of patients \\rith HIV infection \\'as 36 ± 8 years, compared to 48 ± 17 years in those \\rithout HIV infection (p = 0.00(1). These
Table 1- Sensitivity of Sputum Culture and Bronchoscopic Tests in Patients with Pulmonary Tuberculosis*
Test Prebronchoseopic sputum Mycobacterial culture Bronchoalveolar lava~e Acid-fast smear ~I ycobacterial culture Transbronchial biopsy Acid-fast smear Mycobacterial culture Granulomatat Postbronchos
