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

Ralph, Anne P., Yeo, Tsin W., Salome, Cheryl M., Waramori, Govert, Pontororing, Gysje J., Kenangalem, Enny, Sandjaja, , Tjitra, Emiliana, Lumb, Richard, Maguire, Graeme P., Price, Ric N., Chatfield, Mark D., Kelly, Paul M., and Anstey, Nicholas M. (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). pp. 616-626.

[img] PDF (Published Version) - Published Version
Restricted to Repository staff only

View at Publisher Website: http://dx.doi.org/10.1093/infdis/jit248
 
10
5


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 FENO 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.

Item ID: 32291
Item Type: Article (Research - C1)
ISSN: 1537-6613
Keywords: tuberculosis; exhaled nitric oxide; L-arginine; M2 macrophages; biomarker
Funders: National Health and Medical Research Council of Australia (NHMRC), Australian Respiratory Council, Royal Australasian College of Physicians, Wellcome Trust
Projects and Grants: NHMRC Grant 605806, NHMRC Grant 496600
Date Deposited: 29 Apr 2014 23:55
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1116 Medical Physiology > 111699 Medical Physiology not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
92 HEALTH > 9205 Specific Population Health (excl. Indigenous Health) > 920599 Specific Population Health (excl. Indigenous Health) not elsewhere classified @ 50%
Downloads: Total: 5
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page