Assessment of small airways dysfunction with impulse oscillometry, multiple flow nitric oxide and spirometry in the Wessex severe asthma cohort study

Rationale: Asthma is a disease of the conducting airways. Small airway events are poorly reflected by standard lung function. Methods: IOS, spirometry and FeNO measures were made in healthy controls (HC, n=76), non-steroid treated mild asthmatics (MA, n=30), steroid treated step 2/3 asthmatics (ModA, n=35) and treatment-resistant step4/5 severe asthmatics (SA n=71), to assess disease related small airways dysfunction. Group comparisons and correlations were undertaken using both parametric and non-parametric statistical analyses. Results: Maximum airway nitric oxide flux (JawNO) , reflecting central airways inflammation, was increased in MA (median 2740, p<0.001) compared to both HC (640)and SA (700). By contrast, alveolar nitric oxide (CANO), which reflects peripheral airway inflammation, was significantly increased in all asthma groups compared to HC (p<0.05). Increased peripheral resistance was significantly elevated in asthma (p<0.001), with R5-R20>10% in absolute values being present in 53.3% of MA, 74.3% of ModA and 84.5% of SA.. A significant negative correlation was noted between R5-R20 and MEF25-75(r=-0.537), p<0.001),and both parameters correlated with asthma control ACQ6 (p<0.001) and asthma quality of life (p<0.001). Conclusion: Increased small airways resistance and distal inflammation is a feature of asthma with increasing peripheral resistance with disease severity. In SA this is associated with worse asthma control and greater impairment in quality of life. These findings emphasise the importance of the small airways to disease pathophysiology in asthma