title: Impaired pulmonary nitric oxide bioavailability in pulmonary tuberculosis: association with disease severity and delayed mycobacterial clearance with treatment.
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.
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory 0810, Australia. anna.ralph@menzies.edu.au
authors.forename: Anna P
authors.initials: AP
authors.lastname: Ralph
authors.forename: Tsin W
authors.initials: TW
authors.lastname: Yeo
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Salome
authors.forename: Govert
authors.initials: G
authors.lastname: Waramori
authors.forename: Gysje J
authors.initials: GJ
authors.lastname: Pontororing
authors.forename: Enny
authors.initials: E
authors.lastname: Kenangalem
authors.lastname: Sandjaja
authors.forename: Emiliana
authors.initials: E
authors.lastname: Tjitra
authors.forename: Richard
authors.initials: R
authors.lastname: Lumb
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Maguire
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.forename: Mark D
authors.initials: MD
authors.lastname: Chatfield
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kelly
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use; D058491:Bacterial Load; D001682:Biological Availability; D001835:Body Weight; D001944:Breath Tests; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis* / Q000276:immunology*; D011859:Radiography; D012720:Severity of Illness Index; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D009569:Nitric Oxide
keywords: L-arginine; M2 macrophages; biomarker; exhaled nitric oxide; tuberculosis