Exhaled nitric oxide: A biomarker integrating both lung function and airway inflammation changes

Background The increased fraction of exhaled nitric oxide (F eno ) values observed in asthmatic patients are thought to reflect increased airway inflammation. However, F eno values can be affected by airway caliber reduction, representing a bias when using F eno values to assess asthma control. Objective We sought to determine the effect of changes in both airway caliber and inflammation on F eno values using the allergen challenge model. Methods FEV1 and F eno values were measured during early airway responses (EARs) and late airway responses after challenge with house dust mite allergens in 15 patients with mild allergic asthma. Helium and sulfur hexafluoride (SF6 ) phase III expired concentration slopes (SHe and SSF6 , respectively) from single-breath washout tests were measured to identify sites of airway constriction. Results In EARs, FEV1 and F eno value decreases reached 36.8% and 22%, respectively ( P < .001). ΔSHe was greater than ΔSSF6 (+189.4% vs +82.2%, P = .001). In late airway responses FEV1 and F eno value decreases reached 31.7% and 28.7%, respectively ( P < .001), with the same ΔSHe and ΔSSF6 pattern (+155.8% vs +76%, P = .001). Eight hours after the EAR, FEV1 was still decreased ( P < .001), whereas F eno values had returned to baseline. At 24 hours, FEV1 had returned to baseline, with F eno values increased by 38.7% ( P = .04). Conclusion In patients with mild allergic asthma, airway caliber changes modulate changes in F eno values resulting from airway inflammation. Therefore F eno should no longer be considered solely an inflammation biomarker but rather a biomarker that integrates both airway inflammation and lung function changes. Furthermore, early and late phases resulting from allergen exposure were shown to involve similar lung regions.