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(E)NO); 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 > or = 30% in 15 patients with asthma with 80% power. RESULTS: At baseline when clinically stable, after 180 microg of albuterol, forced expiratory volume in 1 s (FEV(1); litres) was 78+/-26% predicted (p=0.009) with increased F(E)NO at 50 ml/s (p=0.01) and J'(awNO) (p=0.02), but C(ANO) was normal compared with the controls. During exacerbation FEV(1) (litres) was 57+/-20% predicted (p=0.02), with increased F(E)NO 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(E)NO at 50 ml/s. C(ANO) was normal.