Volume 98, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant–TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8–26] versus 15 ppb [IQR = 12–24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10–19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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  1. Ralph AP, Anstey NM, Kelly PM, , 2009. Tuberculosis into the 2010s: is the glass half full? Clin Infect Dis 49: 574583. [Google Scholar]
  2. World Health Organization. Global Tuberculosis Report 2015. Geneva: World Health Organization. 2015 (WHO/HTM/TB/2015.22). ISBN 978 92 4 156505 9.
  3. Chan ED, Chan J, Schluger NW, , 2001. What is the role of nitric oxide in murine and human host defense against tuberculosis? Current knowledge. Am J Respir Cell Mol Biol 25: 606612. [Google Scholar]
  4. Aston C, Rom WN, Talbot AT, Reibman J, , 1998. Early inhibition of mycobacterial growth by human alveolar macrophages is not due to nitric oxide. Am J Respir Crit Care Med 157: 19431950. [Google Scholar]
  5. Schon T, Elias D, Moges F, Melese E, Tessema T, Stendahl O, Britton S, Sundqvist T, , 2003. Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis. Eur Respir J 21: 483488. [Google Scholar]
  6. Lim KG, Mottram C, , 2008. The use of fraction of exhaled nitric oxide in pulmonary practice. Chest 133: 12321242. [Google Scholar]
  7. Elmasri M, Romero KM, Gilman RH, Hansel NN, Robinson CL, Baumann LM, Cabrera L, Hamilton RG, Checkley W, PURA Study Investigators; , 2014. Longitudinal assessment of high versus low levels of fractional exhaled nitric oxide among children with asthma and atopy. Lung 192: 305312. [Google Scholar]
  8. Moore DA, 2006. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Engl J Med 355: 15391550. [Google Scholar]
  9. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, Plummer AL, Taylor DR, American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels for Clinical Applications; , 2011. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 184: 602615. [Google Scholar]
  10. Yhi JY, Park DW, Min JH, Park YK, Kim SH, Kim TH, Sohn JW, Yoon HJ, Shin DH, Moon JY, , 2016. Measurement of levels of fractional exhaled nitric oxide in patients with pulmonary tuberculosis. Int J Tuberc Lung Dis 20: 11741180. [Google Scholar]
  11. Ralph AP, 2013. Impaired pulmonary nitric oxide bioavailability in pulmonary tuberculosis: association with disease severity and delayed mycobacterial clearance with treatment. J Infect Dis 208: 616626. [Google Scholar]
  12. Idh J, 2008. Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection. BMC Infect Dis 8: 146. [Google Scholar]
  13. Wang CH, Liu CY, Lin HC, Yu CT, Chung KF, Kuo HP, , 1998. Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible NO synthase upregulation in alveolar macrophages. Eur Respir J 11: 809815. [Google Scholar]
  14. Van Beek SC, Nhung NV, Sy DN, Sterk PJ, Tiemersma EW, Cobelens FG, , 2011. Measurement of exhaled nitric oxide as a potential screening tool for pulmonary tuberculosis. Int J Tuberc Lung Dis 15: 185192. [Google Scholar]
  15. Olin AC, Bake B, Toren K, , 2007. Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers. Chest 131: 18521856. [Google Scholar]
  16. Kim MA, Shin YS, Pham le D, Park HS, , 2014. Adult asthma biomarkers. Curr Opin Allergy Clin Immunol 14: 4954. [Google Scholar]
  17. Barnes PJ, , 2008. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 118: 35463556. [Google Scholar]
  18. O’Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MP, , 2013. The immune response in tuberculosis. Annu Rev Immunol 31: 475527. [Google Scholar]

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  • Received : 30 May 2017
  • Accepted : 26 Feb 2018
  • Published online : 30 Apr 2018

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