The primary aim of this study is to investigate the effects of oral and inhaled administration of L-arginine and of inhaled aminoguanidine on bronchial and alveolar exhaled NO and NO metabolites in exhaled breath condensate, induced sputum, nasal lavage and mouth wash fluid in healthy non-smokers, current smokers and patients with COPD.

Nitric oxide (NO) is produced by resident and inflammatory cells in the respiratory tract by the enzyme NO synthase (NOS), which exists in three isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS. NO production is increased in patients with COPD, and the production of NO under oxidative stress conditions generates reactive nitrogen species that may amplify the inflammatory response in COPD.

Inclusion Criteria:

• Healthy non-smokers

• Normal spirometry (FEV1 >90 % predicted; exhaled NO bigger than or equal to 10 ppb; flow 50 ml/s)

• At risk (current smokers)

  • Normal spirometry, with or without chronic symptoms (cough, sputum production)
  • FEV1 reversibility of <15% after inhaled beta2-agonists*

• Moderate COPD

  • FEV1 greater than or equal to 30% and < 80%
  • FEV1/FVC < 70% predicted
  • FEV1 reversibility of <15% after inhaled beta2-agonists
  • With or without chronic symptoms (cough, sputum production, dyspnea)

• Able to comprehend and grant a written informed consent

Exclusion Criteria:

• Concomitant use or pre-treatment within the last 4 weeks with oral steroids
• Respiratory infection within 4 weeks prior to entry into the trial
• Females who are pregnant or lactating
• History of current or past drug or alcohol abuse