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Alveolar and Airway Sites of Nitric Oxide Inflammation in Treated Asthma

Departments of Pharmacy Services and Radiology, and Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, Lakewood; University of California at Los Angeles, Geffen School of Medicine, Los Angeles; Department of Pediatrics, Miller Children's Hospital at Long Beach Memorial Hospital, Long Beach; University of California at Irvine, School of Medicine, Irvine, California; and University of Toronto, Faculty of Medicine, Toronto, Ontario, Canada

Correspondence and requests for reprints should be addressed to Arthur F. Gelb, M.D., 3650 East South Street, Suite 308, Lakewood, CA 90712. E-mail: afgelb{at}msn.com

The goal of this study was to identify airway and alveolar site(s) of inflammation using exhaled nitric oxide (NO) as a marker in treated patients with asthma, including response to oral corticosteroids, and correlate these sites with expiratory airflow limitation. In 53 (24 male) patients with asthma, age 43 ± 23 years (mean ± SD) and all on inhaled corticosteroids, post 180 µg aerosolized albuterol, FEV₁ was 74 ± 23% predicted and FEV₁/FVC was 68 ± 11%. Exhaled NO at 100 ml/second was 27 ± 23 ppb (p < 0.001 compared with normal, 12 ± 15 ppb). Bronchial NO maximal flux was 2.4 ± 3.1 nl/second (p < 0.001 compared with normal, 0.85 ± 0.55). Alveolar NO concentration was 7.0 ± 7.4 ppb (p = 0.01 compared with the normal value, 3.2 ± 2.0 ppb). There was no significant correlation between FEV₁ % predicted or lung elastic recoil and NO bronchial flux or alveolar concentration. However, there was a weak but significant correlation between NO bronchial flux and alveolar concentration (Spearman r = 0.50, p < 0.001). In 10 subjects with asthma on inhaled corticosteroids, 5 days of 30 mg prednisone resulted in isolated significant decreases in NO alveolar concentration, from 13 ± 10 to 4 ± 4 ppb (p = 0.002). Despite treatment, including inhaled corticosteroids, patients with asthma may have ongoing separate airway and alveolar sites of NO inflammation, the latter responsive to oral corticosteroids.

Key Words: alveolitis • asthma • exhaled nitric oxide • inflammation

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