Peripheral lung function in patients with stable and unstable asthma

Background: Exacerbations of asthma are thought to be caused by airflow obstruction resulting from airway inflammation, bronchospasm, and mucus plugging. Histologic evidence suggests the small airways, including acinar air spaces, are involved; however, this has not been corroborated in vivo by measurements of peripheral small-airway function. Objective: We sought to determine whether asthma severity is linked to small-airway function, particularly in patients with acute severe asthma. Methods: Eighteen subjects admitted for an asthma exacerbation underwent lung function testing, including measures of acinar ventilation heterogeneity (S-acin) and conductive ventilation heterogeneity (S-cond) using the multiple-breath nitrogen washout. Treatment requirement was defined according to Global Initiative for Asthma scores. Data were compared with those obtained in 19 patients with stable asthma. Results: For the asthma exacerbation group, the median FEV1 was 59% of predicted value (95% CI, 45% to 75% of predicted value), the median S-cond value was 185% of predicted value (95% CI, 119% to 245% of predicted value), and the median S-acin value was 225% of predicted value (95% CI, 143% to 392% of predicted value). FEV1 (percent predicted) was correlated with S-acin (percent predicted) values (Spearman rho = -0.67, P =.006) but not with S-cond (percent predicted) values (P >.1). The Global Initiative for Asthma score was significantly related to S-acin (percent predicted) (Spearman rho = 0.59, P = .016) but not to S-cond (percent predicted) values (P >.1). The unstable group was characterized by considerably lower forced vital capacity (P <. 001) and higher S-cond (P =.001) values than the unstable group. In a subgroup of 11 unstable patients who could be reviewed after 4 weeks, FEV1, forced vital capacity, S-acin, and S-cond values showed marked improvements. Conclusion: Our findings suggest that unstable asthma is characterized by a combined abnormality in the acinar and conductive lung zones, both of which are partly reversible. Functional abnormality in the acinar lung zone in particular showed a direct correlation with airflow obstruction and treatment requirement in patients with acute severe asthma.