LAUSR

There is poor understanding of why some patients with asthma experience recurrent exacerbations despite high levels of treatment. We compared measurements of peripheral ventilation heterogeneity and respiratory system mechanics in participants with asthma who were differentiated according to exacerbation history, to ascertain whether peripheral airway dysfunction was related to exacerbations. Three asthmatic groups: "Stable" (no exacerbations for >12 months, n=18), "Exacerbation-prone" (≥1 exacerbation requiring systemic corticosteroids within the last 12 months, but stable for ≥1-month, n=9) and "Treated-exacerbation" (exacerbation requiring systemic corticosteroids within the last 1 month, n=12) were studied. All participants were current non-smokers with <10pack/years smoking history. Spirometry, static lung volumes, ventilation heterogeneity from multi-breath nitrogen washout (MBW) and respiratory system mechanics from oscillometry were measured. The Exacerbation-prone group compared to the Stable group had slightly worse spirometry (FEV1 Z-score -3.58(1.13) vs -2.32(1.06), p=0.03), however acinar ventilation heterogeneity (Sacin Z-score 7.43(8.59) vs 3.63(3.88), p=0.006) and respiratory system reactance (Xrs cmH2O.s.L-1 -2.74(3.82) vs -1.32(1.94), p=0.01) were much worse in this group. The Treated-exacerbation group had worse spirometry but similar small airway function, compared with the Stable group. Patients with asthma who exacerbate have worse small airway function as evidenced by increases in Sacin measured by MBW and delta Xrs from oscillometry, both markers of small airway dysfunction, compared with those that do not.