Impaired pulmonary nitric oxide bioavailability in pulmonary tuberculosis: Association with disease severity and delayed mycobacterial clearance with treatment

Anna Ralph, Tsin Yeo, Cheryl Salome, G Waramori, Gysje Pontororing, E Kenangalem, Sandjaja Sandjaja, E Tjitra, Richard Lumb, G Maguire, Ric Price, Mark Chatfield, Paul Kelly, Nicholas Anstey

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    18 Citations (Scopus)

    Abstract

    Background. Nitric oxide (NO), a key macrophage antimycobacterial mediator that ameliorates immunopathology, is measurable in exhaled breath in individuals with pulmonary tuberculosis. We investigated relationships between fractional exhale NO (FE NO ) and initial pulmonary tuberculosis severity, change during treatment, and relationship with conversion of sputum culture to negative at 2 months. Methods. In Papua, we measured FE NO in patients with pulmonary tuberculosis at baseline and serially over 6 months and once in healthy controls. Treatment outcomes were conversion of sputum culture results at 2 months and time to conversion of sputum microscopy results. Results. Among 200 patients with pulmonary tuberculosis and 88 controls, FE NO was lower for patients with pulmonary tuberculosis at diagnosis (geometric mean FE NO , 12.7 parts per billion [ppb]; 95% confidence interval [CI], 11.6-13.8) than for controls (geometric mean FE NO , 16.6 ppb; 95% CI, 14.2-19.5; P =. 002), fell further after treatment initiation (nadir at 1 week), and then recovered by 6 months (P =. 03). Lower FE NO was associated with more-severe tuberculosis disease, with FE NO directly proportional to weight (P <. 001) and forced vital-capacity (P =. 001) and inversely proportional to radiological score (P =. 03). People whose FE NO increased or remained unchanged by 2 months were 2.7-fold more likely to achieve conversion of sputum culture than those whose FE NO decreased (odds ratio, 2.72; 95% CI, 1.05-7.12; P =. 04). Conclusions. Among patients with pulmonary tuberculosis, impaired pulmonary NO bioavailability is associated with more-severe disease and delayed mycobacterial clearance. Measures to increase pulmonary NO warrant investigation as adjunctive tuberculosis treatments.

    Original languageEnglish
    Pages (from-to)616-626
    Number of pages11
    JournalJournal of Infectious Diseases
    Volume208
    Issue number4
    DOIs
    Publication statusPublished - 2013

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  • Cite this

    Ralph, A., Yeo, T., Salome, C., Waramori, G., Pontororing, G., Kenangalem, E., Sandjaja, S., Tjitra, E., Lumb, R., Maguire, G., Price, R., Chatfield, M., Kelly, P., & Anstey, N. (2013). Impaired pulmonary nitric oxide bioavailability in pulmonary tuberculosis: Association with disease severity and delayed mycobacterial clearance with treatment. Journal of Infectious Diseases, 208(4), 616-626. https://doi.org/10.1093/infdis/jit248