Asthma and lower airway diseaseDifferent patterns of exhaled nitric oxide response to β2-agonists in asthmatic patients according to the site of bronchodilation

BackgroundIn asthmatic patients undergoing airway challenge, fraction of exhaled nitric oxide (Feno) levels decrease after bronchoconstriction. In contrast, model simulations have predicted both decreased and increased Feno levels after bronchodilation, depending on the site of airway obstruction relief.ObjectiveWe sought to investigate whether β2-agonists might induce divergent effects on Feno values in asthmatic patients as a result of airway obstruction relief occurring at different lung depths.MethodsFeno, FEV1, and the slope of phase III of the single-breath washout test (S) of He (SHe) and sulfur hexafluoride (SSF6) were measured in 68 asthmatic patients before and after salbutamol inhalation. SHe and SSF6 decreases reflected preacinar and intra-acinar obstruction relief, respectively. Changes (Δ) were expressed as a percentage from the baseline.ResultsNo Feno change (|ΔFeno| ≤ 10%) was found in 16 patients (mean [SD]: 2.5% [5.2%]; ie, Feno= group); a ΔFeno value of greater than 10% was found in 23 patients (31.7% [20.3%]; ie, the Feno+ group); and a ΔFeno value of less than −10% was found in 29 patients (−31.5% [17.3%]; ie, the Feno− group). All groups had similar ΔFEV1 values. In the Feno= group neither SHe nor SSF6 changed, in the Feno+ group only SHe decreased significantly (−21.8% [SD 28.5%], P = .03), and in the Feno− group both SHe (−29.8% [24.0%], P < .001) and SSF6 (−27.2% [23.3%], P < .001) decreased.DiscussionThree Feno behaviors were observed in response to β2-agonists: a decrease likely caused by relief of an intra-acinar airway obstruction that we propose reflects amplification of nitric oxide back-diffusion, an increase likely associated with a predominant dilation up to the preacinar airways, and Feno stability when obstruction relief involved predominantly the central airways. In combination, these results suggest a new role for Feno in identifying the site of airway obstruction in asthmatic patients.