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American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 316a-317, (2007)
© 2007 American Thoracic Society


Correspondence

Rapid Diagnosis of Smear-negative Tuberculosis by Bronchoalveolar Lavage Enzyme-linked Immunospot

To the Editor:

We read with interest the article by Jafari and colleagues describing the use of an enzyme-linked immunospot assay (ELISPOT) with cells derived from bronchoalveolar lavage (BAL) to diagnose sputum smear-negative tuberculosis (TB) (1). As the authors make clear, differentiation of TB into active, latent, quiescent, or even treated forms can be difficult. This has implications for a test that is reported to separate these groups. For example, in the current study, where subjects were recruited on the basis of pulmonary infiltrates and a medical history compatible with TB, 4 of 12 (33%) cases who were classified as "active TB" lacked culture confirmation but responded to anti-TB therapy. They also had positive tuberculin skin tests (TST) and blood ELISPOTS, but so did a number of the subjects who were felt not to have active TB, including three with "pneumonia" who were finally classified as having latent TB infection (LTBI). It would be instructive to know (1) the criteria used in making a diagnosis of TB, and whether this decision was reached without access to immunological tests; and (2) if subjects with pneumonia, but not active TB, were given treatment for LTBI. In view of the difficulty in distinguishing between stages of TB infection, the finding that this appears possible using BAL-derived cells is exciting. The observation of demonstrable antigen-specific responses in blood, but not in the lung, however, appears contrary to the quoted work of Schwander and coworkers and Silver and coworkers, which describes lung-compartmentalized responses in latently infected subjects (2, 3).

Diagnosing TB in HIV-infected individuals may not be straightforward (4). Using a different methodology, we have previously reported that BAL immunodiagnosis is possible even in advanced HIV infection (5). We are unclear whether the same applies to the authors' ELISPOT technique, where the published literature indicates that positive controls are reproducible, but not that the assay can necessarily detect TB in severe HIV coinfection. We would be interested to know, therefore, the HIV status of the subjects reported in this paper.

The purpose of the study was to assess a rapid method to diagnose TB. All subjects underwent fiberoptic bronchoscopy. This has been shown to significantly improve the microbiological diagnosis of TB, including smear for acid-fast bacilli (AFB) (6). Can the authors please indicate the number of BAL samples that were AFB smear positive, and hence would have aided in rapid diagnosis?

Ronan A. M. Breen, Anne Dunleavy and Marc C. I. Lipman

Royal Free and University College Medical School, London, United Kingdom

FOOTNOTES

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

  1. Jafari C, Ernst M, Kalsdorf B, Greinert U, Diel R, Kirsten D, Marienfeld K, Lalvani A, Lange C. Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot. Am J Respir Crit Care Med 2006;174:1048–1054.[Abstract/Free Full Text]
  2. Schwander SK, Torres M, Carranza CC, Escobedo D, Tary-Lehmann M, Anderson P, Toosi Z, Euner JJ, Rich EA, Sada E. Pulmonary mononuclear cell responses to antigens of Mycobacterium tuberculosis in healthy household contacts of patients with active tuberculosis and healthy. J Immunol 2000;165:1479–1485.[Abstract/Free Full Text]
  3. Silver RF, Zukowski L, Kotake S, Li Q, Pozuelo F, Krywiak A, Larkin R. Recruitment of antigen-specific Th1-like responses to the human lung following bronchoscopic segmental challenge with purified protein derivative of Mycobacterium tuberculosis. Am J Respir Cell Mol Biol 2003;29:117–123.[Abstract/Free Full Text]
  4. Burman WJ, Jones BE. Clinical and radiographic features of HIV-related tuberculosis. Semin Respir Infect 2003;18:263–271.[Medline]
  5. Breen RA, Janossy G, Barry SM, Cropley I, Johnson MA, Lipman MC. Detection of mycobacterial antigen responses in lung but not blood in HIV-tuberculosis co-infected subjects. AIDS 2006;20:1330–1332.[Medline]
  6. Schoch OD, Rieder P, Tueller C, Altpeter E, Zellweger JP, Rieder HL, Krause M, Thurnheer R. Diagnostic yield of sputum, induced sputum, and bronchoscopy after radiologic tuberculosis screening. Am J Respir Crit Care Med 2007;175:80–86.[Abstract/Free Full Text]




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Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2007 American Thoracic Society