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'awNO (nl/sec)] and distal contributions [CA_NO (ppb)].We hypothesized that theBDRreflects the inflammatory status of the larger airways with smooth muscle, and thuswould 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 andeNOat multiple flowswere measured prior and 10 min following inhalation of albuterol. A trumpet-shaped axial diffusion model of NO exchange was used to characterize J'awNO 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 ≥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.