title: Markers of nitric oxide metabolism in sputum and exhaled air are not increased in chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Nitric oxide (NO) is involved in inflammation and host defence of the lung. It has been found in increased concentrations in the airways in asthmatic subjects but its levels in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. A study was undertaken to determine whether markers of NO metabolism (NO in exhaled air, iNOS expression in sputum cells, and nitrite + nitrate (NO2-/NO3-) in sputum supernatant) are increased in subjects with COPD, and whether they correlate with inflammatory indices in induced sputum. The associations of these markers with smoking were also assessed.
  
  
  METHODS
  Sixteen subjects with COPD (median age 66 years, median forced expiratory volume in one second (FEV1) 63% predicted, eight current smokers) and 16 healthy subjects (median age 63 years, median FEV1 113% predicted, eight current smokers) participated in the study. NO was measured during tidal breathing and sputum was induced by inhalation of hypertonic saline.
  
  
  RESULTS
  No differences were observed between subjects with COPD and healthy controls in exhaled NO excretion rate (median 5.15 and 6.25 nmol/min), sputum macrophage iNOS expression (14% and 12%), and sputum supernatant NO2-/NO3- (46 and 73 microM). NO in exhaled air correlated with the percentage of sputum eosinophils in patients with COPD (rho = 0.65, p = 0.009) but not in healthy individuals. Exhaled NO and supernatant NO2-/NO3- levels were lower in healthy smokers than in healthy non/ex-smokers.
  
  
  CONCLUSIONS
  Our findings indicate that NO metabolism is not increased in patients with stable COPD. The close association between exhaled NO levels and sputum eosinophils suggests a role for NO in airway inflammation in COPD. Studies performed during exacerbations may clarify this role.
authors.affiliation: Department of Pulmonology, University Hospital, Groningen, The Netherlands.
authors.forename: S R
authors.initials: SR
authors.lastname: Rutgers
authors.forename: T W
authors.initials: TW
authors.lastname: van der Mark
authors.forename: W
authors.initials: W
authors.lastname: Coers
authors.forename: H
authors.initials: H
authors.lastname: Moshage
authors.forename: W
authors.initials: W
authors.lastname: Timens
authors.forename: H F
authors.initials: HF
authors.lastname: Kauffman
authors.forename: G H
authors.initials: GH
authors.lastname: Koëter
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007958:Leukocyte Count; D008168:Lung / Q000503:physiopathology; D008173:Lung Diseases, Obstructive / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000032:analysis*; D009569:Nitric Oxide / Q000032:analysis*; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis*; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000166:cytology / Q000201:enzymology* / Q000276:immunology
chemical_list: D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II