Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma.
BACKGROUND
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.
Gelb
Arthur F
AF
Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, and Geffen School of Medicine, University of California at Los Angeles Medical Center, Lakewood, California, USA. afgelb@msn.com
George
Steven C
SC
Silkoff
Philip E
PE
Krishnan
Anita
A
Fraser
Christine
C
Taylor
Colleen Flynn
CF
Shinar
Chris M
CM
Maginot
Tamara
T
D000208:Acute Disease; D000368:Aged; D000420:Albuterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001944:Breath Tests / Q000379:methods; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000502:physiology; D000068299:Salmeterol Xinafoate; D013147:Spirometry / Q000379:methods; D014797:Vital Capacity
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D009569:Nitric Oxide; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D011241:Prednisone