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'aw NO) 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'aw NO(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 m g 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'aw NO 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 C ANO 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. C ANO 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 signifi cantly with age ≥ 60 years, whereas J'aw NO did not. We suspect the increase in C ANO was due to a decrease in capillary blood volume with reduced NO diffusion, which is also refl ected in increased FENO. Inhaled budesonide had no anti-NO-mediated infl ammatory effect. Age-matched control subjects will be needed in NO comparative studies. Trial registry: ClinicalTrials.gov; No.: NCT00576069 and NCT00568347; URL:www.clinicaltrials. gov.