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

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.