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 (FENO); 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 beta(2)-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 mu g of albuterol, forced expiratory volume in 1 s (FEV1; litres) was 78+/-26% predicted (p=0.009) with increased FENO 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 FENO 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 FENO at 50 ml/s. C-ANO was normal.