Small airways dysfunction is associated with increased exacerbations in patients with asthma.

There is a 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 mo, n = 18), "exacerbation-prone" (≥1 exacerbation requiring systemic corticosteroids within the last 12 mo, but stable for ≥1-mo, n = 9), and "treated-exacerbation" (exacerbation requiring systemic corticosteroids within the last 1 mo, n = 12) were studied. All participants were current nonsmokers with <10 pack yr smoking history. Spirometry, static lung volumes, ventilation heterogeneity from multibreath nitrogen washout (MBNW), and respiratory system mechanics from oscillometry were measured. The exacerbation-prone group compared with the stable group had slightly worse spirometry [forced expired volume in 1 s or 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 MBNW and ΔXrs from oscillometry, both markers of small airway dysfunction, compared with those that do not.NEW & NOTEWORTHY This study assessed the relationship between peripheral airway function, measured by multiple breath nitrogen washout and oscillometry impedance, and exacerbation history. We found that those with a history of exacerbation in the last year had worse peripheral airway function, whereas those recently treated for an asthma exacerbation had peripheral airway function that was comparable to the stable group. These findings implicate active peripheral airway dysfunction in the pathophysiology of an asthma exacerbation.

Ventilation heterogeneity in the acinar and conductive zones of the normal ageing lung.

RATIONALE: Small airways function studies in lung disease have used three promising multiple breath washout (MBW) derived indices: indices of ventilation heterogeneity in the acinar (S(acin)) and conductive (S(cond)) lung zones, and the lung clearance index (LCI). Since peripheral lung structure is known to change with age, ventilation heterogeneity is expected to be affected too. However, the age dependence of the MBW indices of ventilation heterogeneity in the normal lung is unknown. OBJECTIVES: The authors systematically investigated S(acin), S(cond) or LCI as a function of age, testing also the robustness of these relationships across two laboratories. METHODS: MBW tests were performed by never-smokers (50% men) in the age range 25-65 years, with data gathered across two laboratories (n=120 and n=60). For comparison with the literature, the phase III slopes from classical single breath washout tests were also acquired in one group (n=120). MEASUREMENTS AND MAIN RESULTS: All three MBW indices consistently increased with age, representing a steady worsening of ventilation heterogeneity in the age range 25-65. Age explained 7-16% of the variability in S(acin) and S(cond) and 36% of the variability in LCI. There was a small but significant gender difference only for S(acin). Classical single breath washout phase III slopes also showed age dependencies, with gender effects depending on the normalisation method used. CONCLUSIONS: With respect to the clinical response, age is a small but consistent effect that needs to be factored in when using the MBW indices for the detection of small airways abnormality in disease.