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Increased nitric oxide concentrations in the small airway of older normal subjects.

BACKGROUND
There is a paucity of normal-age stratified data for fraction of exhaled nitric oxide (Feno). Our goal was to obtain normal data for large-airway nitric oxide flux (J'awno) and small-airway and/or alveolar nitric oxide concentration (Cano) in nonsmoking, healthy, adult subjects of various ages.


METHODS
In 106 normal volunteer subjects (60 women) aged 55 ± 20 years (mean ± SD), Feno (parts per billion [ppb]) was measured at 50, 100, 150, and 200 mL/s and J'awno (nL/s) and Cano (ppb) were calculated using a two-compartment model with correction for axial nitric oxide (NO) back diffusion. Fourteen older normal subjects were also treated with inhaled corticosteroid (540 μg budesonide bid) for 14 days.


RESULTS
We studied 34 younger normal subjects (17 women) aged 18 to 39 years (younger), 26 middle-aged normal subjects (22 women) aged 40 to 59 years (middle-aged), and 46 older normal subjects (21 women) aged 60 to 86 years (older). Feno at 50 mL/s in the younger group was 21 (14-28) ppb (median, 1-3 interquartile); in the middle-aged group it was 22 (18-30) ppb, and in the older group it was 27 (21-33) ppb, (analysis of variance [ANOVA]) P = .02. For Feno, the younger vs older groups was (Mann-Whitney) P = .03, and Feno in the combined younger and middle-aged groups was 21 (15-29) ppb vs 27 (21-33) ppb, P = .006 for the older group. Corrected J'awno in the younger group was 1.5 (1.0-2.1) nL/s; in the middle-aged group it was 1.4 (1.0-2.0) nL/s, and in the older group it was 1.8 (1.2-2.4) nL/s, (ANOVA) P = .3. Corrected Cano in the younger group was 1.9 (0.8-3.0) ppb; in the middle-aged group it was 2.8 (0.8-5.1) ppb, and in the older group it was 3.9 (1.4-6.6) ppb, (ANOVA) P = .02. Cano in the younger vs older groups was P = .003, and the combined younger and middle-aged group result was 2.0 (0.8-3.8) vs 3.9 (1.4-6.6), P = .01 in the older group. There was no change in NO gas exchange with inhaled corticosteroids.


CONCLUSIONS
In nonsmoking healthy subjects with normal spirometry, Feno at 50 mL/s and Cano increased significantly with age ≥ 60 years, whereas J'awno did not. We suspect the increase in Cano was due to a decrease in capillary blood volume with reduced NO diffusion, which is also reflected in increased Feno. Inhaled budesonide had no anti-NO-mediated inflammatory effect. Age-matched control subjects will be needed in NO comparative studies.


TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT00576069 and NCT00568347; URL: www.clinicaltrials.gov.