Exahaled NO and small airway function in asthma and cystic fibrosis

Sammanfattning: Background: Asthma and cystic fibrosis (CF) are chronic inflammatory airway disorders known to involve the peripheral airways. Non-invasive tests sensitive to peripheral airway function and inflammation are therefore of high priority. Multiple breath inert gas washout (MBW) is a test sensitive to small airway function and exhaled nitric oxide (NO) reflects airway inflammation in asthma. Aim: To use exhaled NO in combination with MBW to assess the contribution of small airway inflammation and dysfunction in paediatric asthma and CF in order to potentially allow for earlier intervention and more successful management of these conditions in the future. Results: CF subjects had reduced levels of nasal and exhaled NO. All but three children with CF had abnormally elevated LCI. Low levels of NO were associated with impaired airway function, chronic infection with Ps. Aeruginosa, severe genotypes and the fatty acid deficiency characteristic for CF subjects. Low levels of alveolar NO, albeit not lower in CF than in healthy controls, were associated with increased systemic inflammation and chronic bacterial airway colonisation. LCI, Scond, and Sacin were all significantly elevated in children with asthma and Scond was the marker that most significantly differentiated the asthmatic children from the healthy controls. Increased Scond was associated with increased levels of exhaled NO and airway hyper-responsiveness and Sacin correlated with alveolar NO. Conclusions: This thesis provides further evidence of small airway involvement in both paediatric asthma and CF. The findings of clinically significant dysfunction of the small conducting airways in paediatric asthma and the associations between small airway dysfunction, increased levels of exhaled NO and airway hyper-responsiveness are novel findings. In CF, low levels of exhaled NO are linked to small airway dysfunction. These findings provide new exciting insights into the pathology and pathophysiology of paediatric asthma and CF and may allow for earlier and better targeted interventions.