An elevated bronchodilator response predicts large airway inflammation in mild asthma

Exhaled nitric oxide (eNO) is elevated in asthmatics and is a purported marker of airway inflammation. The bronchodilator response (BDR) has also been shown to correlate with markers of airway inflammation, including eNO at 50 ml/sec (FE(NO,50)) which is comprised of NO from both the proximal and distal airways. Using eNO at multiple flows and a two-compartment model of NO exchange, the eNO signal can be partitioned into its proximal [J'aw(NO) (nl/sec)] and distal contributions [CA(NO) (ppb)]. We hypothesized that the BDR reflects the inflammatory status of the larger airways with smooth muscle, and thus would correlate with J'aw(NO). In 179 predominantly (95%) Hispanic children with mild asthma (69 steroid naïve), and 21 non-asthmatic non-atopic controls, spirometry and eNO at multiple flows were measured prior and 10 min following inhalation of albuterol. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'aw(NO) and CA(NO). The BDR correlated moderately (r = 0.44) with proximal airway NO (J'aw(NO)), but weakly (r = 0.26) with distal airway/alveolar NO (CA(NO)), and only in inhaled corticosteroid naïve asthmatics. A BDR cut point as low as >or=8% had a positive predictive value of 83% for predicting an elevated J'aw(NO) or FE(NO,50). We conclude that the BDR reflects inflammation in the large airways, and may be an effective clinical tool to predict elevated large airway inflammation.