Impaired Pulmonary Nitric Oxide Bioavailability in Pulmonary Tuberculosis

Association With Disease Severity and Delayed Mycobacterial Clearance With Treatment

Anna Ralph, Tsin Yeo, Cheryl Salome, Govert Waramoi, Gysje Pontororing, Enny Kenangalem, Sandjaja, Emiliana Tjitra, R Lumb, Graeme P Maguire, Ric Price, Mark Chatfield, Paul Kelly, Nicholas Anstey

Research output: Contribution to journalArticleResearchpeer-review

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 (FENO) 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 FENO 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, FENO was lower for patients with pulmonary tuberculosis at diagnosis (geometric mean FENO, 12.7 parts per billion [ppb]; 95% confidence interval [CI], 11.6-13.8) than for controls (geometric mean FENO, 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 FENO was associated with more-severe tuberculosis disease, with FENO 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 FENO 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. � The Author 2013.
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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Pulmonary Tuberculosis
Biological Availability
Nitric Oxide
Sputum
Lung
Confidence Intervals
Tuberculosis
Therapeutics
Vital Capacity
Microscopy
Macrophages
Odds Ratio
Weights and Measures

Cite this

Ralph, Anna ; Yeo, Tsin ; Salome, Cheryl ; Waramoi, Govert ; Pontororing, Gysje ; Kenangalem, Enny ; Sandjaja ; Tjitra, Emiliana ; Lumb, R ; Maguire, Graeme P ; Price, Ric ; Chatfield, Mark ; Kelly, Paul ; Anstey, Nicholas. / Impaired Pulmonary Nitric Oxide Bioavailability in Pulmonary Tuberculosis : Association With Disease Severity and Delayed Mycobacterial Clearance With Treatment. In: Journal of Infectious Diseases. 2013 ; Vol. 208, No. 4. pp. 616-626.
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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 (FENO) 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 FENO 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, FENO was lower for patients with pulmonary tuberculosis at diagnosis (geometric mean FENO, 12.7 parts per billion [ppb]; 95{\%} confidence interval [CI], 11.6-13.8) than for controls (geometric mean FENO, 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 FENO was associated with more-severe tuberculosis disease, with FENO 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 FENO 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. � The Author 2013.",
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author = "Anna Ralph and Tsin Yeo and Cheryl Salome and Govert Waramoi and Gysje Pontororing and Enny Kenangalem and Sandjaja and Emiliana Tjitra and R Lumb and Maguire, {Graeme P} and Ric Price and Mark Chatfield and Paul Kelly and Nicholas Anstey",
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Impaired Pulmonary Nitric Oxide Bioavailability in Pulmonary Tuberculosis : Association With Disease Severity and Delayed Mycobacterial Clearance With Treatment. / Ralph, Anna; Yeo, Tsin; Salome, Cheryl; Waramoi, Govert; Pontororing, Gysje; Kenangalem, Enny; Sandjaja; Tjitra, Emiliana; Lumb, R; Maguire, Graeme P; Price, Ric; Chatfield, Mark; Kelly, Paul; Anstey, Nicholas.

In: Journal of Infectious Diseases, Vol. 208, No. 4, 2013, p. 616-626.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Impaired Pulmonary Nitric Oxide Bioavailability in Pulmonary Tuberculosis

T2 - Association With Disease Severity and Delayed Mycobacterial Clearance With Treatment

AU - Ralph, Anna

AU - Yeo, Tsin

AU - Salome, Cheryl

AU - Waramoi, Govert

AU - Pontororing, Gysje

AU - Kenangalem, Enny

AU - Sandjaja, null

AU - Tjitra, Emiliana

AU - Lumb, R

AU - Maguire, Graeme P

AU - Price, Ric

AU - Chatfield, Mark

AU - Kelly, Paul

AU - Anstey, Nicholas

PY - 2013

Y1 - 2013

N2 - 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 (FENO) 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 FENO 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, FENO was lower for patients with pulmonary tuberculosis at diagnosis (geometric mean FENO, 12.7 parts per billion [ppb]; 95% confidence interval [CI], 11.6-13.8) than for controls (geometric mean FENO, 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 FENO was associated with more-severe tuberculosis disease, with FENO 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 FENO 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. � The Author 2013.

AB - 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 (FENO) 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 FENO 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, FENO was lower for patients with pulmonary tuberculosis at diagnosis (geometric mean FENO, 12.7 parts per billion [ppb]; 95% confidence interval [CI], 11.6-13.8) than for controls (geometric mean FENO, 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 FENO was associated with more-severe tuberculosis disease, with FENO 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 FENO 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. � The Author 2013.

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