Association between peripheral airway function and neutrophilic inflammation in asthma

Background and objective Small airway dysfunction is associated with asthma severity and control, but its association with airway inflammation is unknown. The aim was to determine the association between sputum inflammatory cells and the site of small airway dysfunction, measured by multiple breath nitrogen washout in convection-dependent (Scond) and more peripheral diffusion-dependent (Sacin) airways. Methods Fifty-three (20-67 years) subjects with asthma on inhaled corticosteroid (ICS) treatment were characterized by spirometry, Scond, Sacin and induced sputum differential counts. %Predicted values for Scond and Sacin were calculated from published reference equations to adjust for the effects of age. Univariate correlations were assessed using the Spearman test. Multivariate linear regressions were performed to account for potential confounders, including age, gender, disease duration, body mass index and ICS dose. Results Sacin (%predicted) correlated significantly with neutrophil% (r_s = 0.33, P = 0.02), ICS dose (r_s = -0.28, P = 0.04) and age (r_s = 0.27, P = 0.05). In multivariate analysis, Sacin related only to neutrophil% (adjusted R² = 0.18, P = 0.001). Scond (%predicted) correlated significantly only with eosinophil% (r_s = 0.39, P = 0.004). There was a trend for a negative relationship with ICS dose (r_s = -0.26, P = 0.06). In multivariate analysis, Scond related to eosinophil% and ICS dose independently (adjusted R² = 0.12, P = 0.02). Conclusions Acinar and conductive airway dysfunction is associated with different inflammatory profiles in asthmatic airways, independently of the effects of age and disease duration. The association between acinar airway dysfunction and neutrophilic airway inflammation may have implications for asthma treatment.