Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma

Introduction: Central airway nitric oxide flux (J′_awNO) and peripheral airway/alveolar nitric oxide concentration (C_ANO) during asthma exacerbation has not been investigated after correction for axial NO back-diffusion. Methods: After measuring exhaled NO (fraction of exhaled nitric oxide (F_ENO); ppb) at 50, 100, 150 and 200 ml/s, J′_awNO (nl/s) and C_ANO (ppb) were calculated using the two-compartment model and corrected for axial NO back-diffusion. Fifteen (8 males), non-smoking, patients with moderate-to-severe treated (inhaled corticosteroid (ICS) and inhaled long-acting β₂-agonist (LABA)) asthma, age 57±13 years (mean±SD), were studied at baseline, during exacerbation prior to oral corticosteroid, and during recovery after an 8 day tapering prednisone course. Based on earlier asthma studies without correction, it was hypothesised that with correction for NO axial back-diffusion, the incidence of abnormal J′_awNO and C _ANO at baseline and after exacerbation would be ≥30% in 15 patients with asthma with 80% power. Results: At baseline when clinically stable, after 180 μg of albuterol, forced expiratory volume in 1 s (FEV ₁; litres) was 78±26% predicted (p=0.009) with increased F_ENO at 50 ml/s (p=0.01) and J′_awNO (p=0.02), but C_ANO was normal compared with the controls. During exacerbation FEV₁ (litres) was 57±20% predicted (p=0.02), with increased F_ENO at 50 ml/s (p=0.01) and J′_awNO (p=0.004), but C_ANO was normal. Recovery results were similar to baseline. Two of 15 patients with asthma always had normal exhaled NO gas exchange. Conclusions: The central airways were the major site of abnormal NO flux in 13 of 15 patients with moderate - severe asthma when stable and during exacerbation and could be easily detected with abnormal F_ENO at 50 ml/s. C_ANO was normal. Clinical trial number: NCT00576069.