title: Utility of exhaled nitric oxide as a noninvasive biomarker of lung inflammation in a disease model.
abstract: There is a great deal of interest in developing less invasive markers for monitoring airway inflammation and the effect of possible novel anti-inflammatory therapies that may take time to impact on disease pathology. Exhaled nitric oxide (eNO) has been shown to be a reproducible, noninvasive indicator of the inflammatory status of the airway in the clinic. The aim of the present study was to determine the usefulness of measuring eNO as a marker of the anti-inflammatory impact of glucocorticoid and an inhibitor of kappaB kinase-2 (IKK-2) inhibitor 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), in a pre-clinical model of airway inflammation. Rats were given vehicle, budesonide or TPCA-1 prior to exposure to lipopolysaccharide, previously shown to induce an increase in eNO and airway neutrophilia/eosinophilia. Comparison of the effect of the two compounds on inflammatory components demonstrated a significant correlation between the impact on eNO and inflammatory cell burden in the airway. The current study demonstrates the usefulness of profiling potential disease-modifying therapies on exhaled nitric oxide levels and the way in which an effect on this noninvasive biomarker relates to effects on pathological parameters such as lung cellularity. Information from studies such as the current one would suggest that the measurement of exhaled nitric oxide has potential for monitoring inflammatory status in lung tissue.
authors.affiliation: Respiratory Pharmacology Group, Imperial College London, Faculty of Medicine, National Heart & Lung Institute, Dovehouse Street, London, SW3 6LY, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Birrell
authors.forename: K
authors.initials: K
authors.lastname: McCluskie
authors.forename: E
authors.initials: E
authors.lastname: Hardaker
authors.forename: R
authors.initials: R
authors.lastname: Knowles
authors.forename: M G
authors.initials: MG
authors.lastname: Belvisi
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism*; D019819:Budesonide / Q000494:pharmacology; D004195:Disease Models, Animal; D045853:Exhalation; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011014:Pneumonia / Q000175:diagnosis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012137:Respiratory System / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D000577:Amides; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D008070:Lipopolysaccharides; D013876:Thiophenes; D009569:Nitric Oxide; D019819:Budesonide; C499326:2-((aminocarbonyl)amino)-5-(4-fluorophenyl)-3-thiophenecarboxamide