title: Airway nitric oxide release is reduced after PBS inhalation in asthma.
abstract: Exhaled nitric oxide (NO) is elevated in asthma, but the underlying mechanisms remain poorly understood. Recent results in subjects with asthma have reported a decrease in exhaled breath pH and ammonia, as well as altered expression and activity of glutaminase in both alveolar and airway epithelial cells. This suggests that pH-dependent nitrite conversion to NO may be a source of exhaled NO in the asthmatic airway epithelium. However, the anatomic location (i.e., airway or alveolar region) of this pH-dependent NO release has not been investigated and could impact potential therapeutic strategies. We quantified airway (proximal) and alveolar (peripheral) contributions to exhaled NO at baseline and then after PBS inhalation in stable (mild-intermittent to severe) asthmatic subjects (20-44 yr old; n = 9) and healthy controls (22-41 yr old; n = 6). The mean (SD) maximum airway wall flux (pl/s) and alveolar concentration (ppb) at baseline in asthma subjects and healthy controls was 2,530 (2,572) and 5.42 (7.31) and 1,703 (1,567) and 1.88 (1.29), respectively. Compared with baseline, there is a significant decrease in the airway wall flux of NO in asthma as early as 15 min and continuing for up to 60 min (maximum -28% at 45 min) after PBS inhalation without alteration of alveolar concentration. Healthy control subjects did not display any changes in exhaled NO. We conclude that elevated airway NO at baseline in asthma is reduced by inhaled PBS. Thus airway NO may be, in part, due to nitrite conversion to NO and is consistent with airway pH dysregulation in asthma.
authors.affiliation: Dept. of Biomedical Engineering, University of California, Irvine, CA 92697-2715, USA.
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Shin
authors.forename: David A
authors.initials: DA
authors.lastname: Shelley
authors.forename: Edward M
authors.initials: EM
authors.lastname: Henderson
authors.forename: Anne
authors.initials: A
authors.lastname: Fitzpatrick
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.forename: Steven C
authors.initials: SC
authors.lastname: George
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000378:metabolism*; D001944:Breath Tests; D001985:Bronchial Provocation Tests; D002021:Buffers; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism*; D012965:Sodium Chloride
chemical_list: D002021:Buffers; D009569:Nitric Oxide; D012965:Sodium Chloride