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Sputum induction for the diagnosis of pulmonary tuberculosis: a systematic review and meta-analysis

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Abstract

Sputum induction (SI) has been proposed as the optimal sample collection method for patients with paucibacillary tuberculosis (TB). Studies reporting the culture of Mycobacterium tuberculosis from SI were reviewed. A random-effects meta-analysis of diagnostic yield (numerator M. tuberculosis SI culture-positive cases; denominator all culture-positive cases) was conducted. Diagnostic yields (95% confidence intervals, CIs) were displayed as Forest plots. Heterogeneity was evaluated using Chi-squared and I-squared tests and meta-regression analysis. Ninety publications were screened, 28 full-text papers reviewed, and 17 analyzed. Collectively, n = 627 SI culture-positive cases among n = 975 culture-confirmed TB cases were reported. The diagnostic yield of SI ranged from 35 to 95%. The pooled diagnostic yield was 74% (CI 65–81%), with significant heterogeneity (p < 0.0001, I2 = 86%). There were no statistically significant differences in the yield between sub-groups defined by human immunodeficiency virus (HIV) prevalence or age. Univariate analysis demonstrated that the use of fiberoptic bronchoscopy (FOB) as the comparator method was associated with a 22% reduction (CI 2–42%) in the diagnostic yield of SI. However, after adjustment for confounding, the meta-regression analysis showed that FOB usage (p = 0.21) and saline concentration (p = 0.31) were not independently associated with the diagnostic yield. SI will detect approximately three-quarters of M. tuberculosis culture-positive cases under study conditions. Significant heterogeneity in the diagnostic yield was not explained by HIV prevalence, age, or the use of FOB as the comparator method. The use of a particular nebulized saline concentration for SI cannot be recommended on the basis of this meta-regression analysis.

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References

  1. World Health Organization (WHO) (2009) Global tuberculosis control—epidemiology, strategy, financing. WHO report 2009. WHO/HTM/TB/2009.411. WHO, Geneva, Switzerland. Available online at: http://www.who.int/tb/publications/global_report/2009/en/index.html

  2. Marais BJ, Hesseling AC, Gie RP, Schaaf HS, Enarson DA, Beyers N (2006) The bacteriologic yield in children with intrathoracic tuberculosis. Clin Infect Dis 42(8):e69–e71

    Article  PubMed  CAS  Google Scholar 

  3. Harries AD, Maher D, Nunn P (1998) An approach to the problems of diagnosing and treating adult smear-negative pulmonary tuberculosis in high-HIV-prevalence settings in sub-Saharan Africa. Bull World Health Organ 76(6):651–662

    PubMed  CAS  Google Scholar 

  4. Dickson SJ, Brent A, Davidson RN, Wall R (2003) Comparison of bronchoscopy and gastric washings in the investigation of smear-negative pulmonary tuberculosis. Clin Infect Dis 37(12):1649–1653

    Article  PubMed  Google Scholar 

  5. Chan HS, Sun AJ, Hoheisel GB (1990) Bronchoscopic aspiration and bronchoalveolar lavage in the diagnosis of sputum smear-negative pulmonary tuberculosis. Lung 168(4):215–220

    Article  PubMed  CAS  Google Scholar 

  6. Dave J, Wilkins EG, Hickey MM (1989) Gastric washing smears—help or hindrance? Tubercle 70(2):151–152

    Article  PubMed  CAS  Google Scholar 

  7. Elliott RC, Reichel J (1963) The efficacy of sputum specimens obtained by nebulization versus gastric aspirates in the bacteriologic diagnosis of pulmonary tuberculosis. A comparative study. Am Rev Respir Dis 88:223–227

    PubMed  CAS  Google Scholar 

  8. Al Zahrani K, Al Jahdali H, Poirier L, René P, Menzies D (2001) Yield of smear, culture and amplification tests from repeated sputum induction for the diagnosis of pulmonary tuberculosis. Int J Tuberc Lung Dis 5(9):855–860

    PubMed  CAS  Google Scholar 

  9. Brown M, Varia H, Bassett P, Davidson RN, Wall R, Pasvol G (2007) Prospective study of sputum induction, gastric washing, and bronchoalveolar lavage for the diagnosis of pulmonary tuberculosis in patients who are unable to expectorate. Clin Infect Dis 44(11):1415–1420

    Article  PubMed  Google Scholar 

  10. Jones FL Jr (1966) The relative efficacy of spontaneous sputa, aerosol-induced sputa, and gastric aspirates in the bacteriologic diagnosis of pulmonary tuberculosis. Dis Chest 50(4):403–408

    Article  PubMed  Google Scholar 

  11. Kawada H, Suzuki N, Takeda Y, Toyoda E, Takahara M, Kobayashi N, Suzuki T, Kudo K, Kabe J (1996) The usefulness of induced sputum in the diagnosis of pulmonary tuberculosis. Kekkaku 71(11):603–606

    PubMed  CAS  Google Scholar 

  12. Anderson C, Inhaber N, Menzies D (1995) Comparison of sputum induction with fiber-optic bronchoscopy in the diagnosis of tuberculosis. Am J Respir Crit Care Med 152(5 Pt 1):1570–1574

    PubMed  CAS  Google Scholar 

  13. Hatherill M, Hawkridge T, Zar HJ, Whitelaw A, Tameris M, Workman L, Geiter L, Hanekom WA, Hussey G (2009) Induced sputum or gastric lavage for community-based diagnosis of childhood pulmonary tuberculosis? Arch Dis Child 94(3):195–201

    Article  PubMed  CAS  Google Scholar 

  14. Conde MB, Soares SL, Mello FC, Rezende VM, Almeida LL, Reingold AL, Daley CL, Kritski AL (2000) 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 162(6):2238–2240

    PubMed  CAS  Google Scholar 

  15. Pizzichini E, Pizzichini MM, Leigh R, Djukanović R, Sterk PJ (2002) Safety of sputum induction. Eur Respir J Suppl 37:9s–18s

    PubMed  CAS  Google Scholar 

  16. Djukanović R, Sterk PJ, Fahy JV, Hargreave FE (2002) Standardised methodology of sputum induction and processing. Eur Respir J Suppl 37:1s–2s

    Article  PubMed  Google Scholar 

  17. Vignola AM, Rennar SI, Hargreave FE, Fah JV, Bonsignore MR, Djukanović R, Sterk PJ (2002) Standardised methodology of sputum induction and processing. Future directions. Eur Respir J Suppl 37:51s–55s

    PubMed  CAS  Google Scholar 

  18. Scheicher ME, Terra Filho J, Vianna EO (2003) Sputum induction: review of literature and proposal for a protocol. Sao Paulo Med J 121(5):213–219

    Article  PubMed  Google Scholar 

  19. Fujita A, Murata K, Takamori M (2009) Novel method for sputum induction using the Lung Flute in patients with suspected pulmonary tuberculosis. Respirology 14(6):899–902

    Article  PubMed  Google Scholar 

  20. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed  Google Scholar 

  21. World Health Organization (WHO) (2000) Second generation surveillance for HIV: the next decade. WHO, Geneva, Switzerland. Available online at: http://www.who.int/reproductivehealth/publications/rtis/CDS_CSR_EDC_2000_5/en/index.html

  22. Hensler NM, Spivey CG Jr, Dees TM (1961) The use of hypertonic aerosol in production of sputum for diagnosis of tuberculosis. Comparison with gastric specimens. Dis Chest 40:639–642

    Article  PubMed  CAS  Google Scholar 

  23. Yue WY, Cohen SS (1967) Sputum induction by newer inhalation methods in patients with pulmonary tuberculosis. Dis Chest 51(6):614–620

    Article  PubMed  CAS  Google Scholar 

  24. Zar HJ, Tannenbaum E, Apolles P, Roux P, Hanslo D, Hussey G (2000) Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa. Arch Dis Child 82(4):305–308

    Article  PubMed  CAS  Google Scholar 

  25. Zar HJ, Hanslo D, Apolles P, Swingler G, Hussey G (2005) Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study. Lancet 365(9454):130–134

    Article  PubMed  Google Scholar 

  26. Morse M, Kessler J, Albrecht S, Kim R, Thakur R, Nthobatsang R, Radisowa K, Maunatlala C, Yang W, Macgregor RR, Friedman H (2008) Induced sputum improves the diagnosis of pulmonary tuberculosis in hospitalized patients in Gaborone, Botswana. Int J Tuberc Lung Dis 12(11):1279–1285

    PubMed  CAS  Google Scholar 

  27. McWilliams T, Wells AU, Harrison AC, Lindstrom S, Cameron RJ, Foskin E (2002) Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis. Thorax 57(12):1010–1014

    Article  PubMed  CAS  Google Scholar 

  28. Ganguly KC, Hiron MM, Mridha ZU, Biswas M, Hassan MK, Saha SC, Rahman MM (2008) Comparison of sputum induction with broncho-alveolar lavage in the diagnosis of smear-negative pulmonary tuberculosis. Mymensingh Med J 17(2):115–123

    PubMed  CAS  Google Scholar 

  29. Bell DJ, Dacombe R, Graham SM, Hicks A, Cohen D, Chikaonda T, French N, Molyneux ME, Zijlstra EE, Squire SB, Gordon SB (2009) Simple measures are as effective as invasive techniques in the diagnosis of pulmonary tuberculosis in Malawi. Int J Tuberc Lung Dis 13(1):99–104

    PubMed  CAS  Google Scholar 

  30. Beck GJ, Nanda K (1962) Use of superheated saline aerosols as a diagnostic measure in pulmonary tubercuosis. A preliminary report. Dis Chest 42:74–78

    Article  PubMed  CAS  Google Scholar 

  31. Schoch OD, Rieder P, Tueller C, Altpeter E, Zellweger JP, Rieder HL, Krause M, Thurnheer R (2007) Diagnostic yield of sputum, induced sputum, and bronchoscopy after radiologic tuberculosis screening. Am J Respir Crit Care Med 175(1):80–86

    Article  PubMed  Google Scholar 

  32. Vargas D, García L, Gilman RH, Evans C, Ticona E, Navincopa M, Luo RF, Caviedes L, Hong C, Escombe R, Moore DA (2005) Diagnosis of sputum-scarce HIV-associated pulmonary tuberculosis in Lima, Peru. Lancet 365(9454):150–152

    Article  PubMed  Google Scholar 

  33. Riso R, Mudido PM, Karamagi C, Whalen C (2005) The diagnosis of childhood tuberculosis in an HIV-endemic setting and the use of induced sputum. Int J Tuberc Lung Dis 9(7):716–726

    Google Scholar 

  34. Owens S, Abdel-Rahman IE, Balyejusa S, Musoke P, Cooke RP, Parry CM, Coulter JB (2007) Nasopharyngeal aspiration for diagnosis of pulmonary tuberculosis. Arch Dis Child 92(8):693–696

    Article  PubMed  CAS  Google Scholar 

  35. Wills PJ, Hall RL, Chan W, Cole PJ (1997) Sodium chloride increases the ciliary transportability of cystic fibrosis and bronchiectasis sputum on the mucus-depleted bovine trachea. J Clin Invest 99(1):9–13

    Article  PubMed  CAS  Google Scholar 

  36. Geldenhuys HD, Kleynhans W, Buckerfield N, Tameris M, Gonzalez Y, Mahomed H, Hussey G, Hanekom W, Hatherill M (2011) Safety and tolerability of sputum induction in adolescents and adults with suspected pulmonary tuberculosis. Eur J Clin Microbiol Infect Dis (in press)

  37. Schoeffel RE, Anderson SD, Altounyan RE (1981) Bronchial hyperreactivity in response to inhalation of ultrasonically nebulised solutions of distilled water and saline. Br Med J (Clin Res Ed) 283(6302):1285–1287

    Article  CAS  Google Scholar 

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Financial support

Y.G.-A. is the recipient of a SATVI Masters Scholarship and M.H. and W.H. are supported by a National Institutes of Health (NIH) grant (1R01AI075603-01).

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All authors: no conflicts.

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Correspondence to M. Hatherill.

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Y. Gonzalez-Angulo contributed to the design of the study, data collection, data analysis, and wrote the final manuscript; C.S. Wiysonge contributed to the design of the study, data analysis, and writing the manuscript; H. Geldenhuys contributed to writing the manuscript; W. Hanekom contributed to writing and editing the manuscript; H. Mahomed contributed to writing and editing the manuscript; G. Hussey contributed to writing and editing the manuscript; M. Hatherill contributed to the design of the study, data analysis, and writing of the final manuscript.

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Gonzalez-Angulo, Y., Wiysonge, C.S., Geldenhuys, H. et al. Sputum induction for the diagnosis of pulmonary tuberculosis: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 31, 1619–1630 (2012). https://doi.org/10.1007/s10096-011-1485-6

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  • DOI: https://doi.org/10.1007/s10096-011-1485-6

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