Using the two-compartment NO model as previously described23 and without correction for NO axial back-diffusion,33,34 we,37,38 Berry et al,105 van Veen et al,106 Brindicci et al,11 and other investigators34-40 have noted increased J’awNO and increased CANO in mild and moderate-to-severe clinically stable asthmatics. Using similar NO modeling23 and without correction for NO axial back-diffusion,33,34 Högman et al107 and Brindicci et al12 reported increased J’awNO, as well as increased CANO, in clinically stable COPD patients compared with controls. However, in the study by Brindicci et al,12 their healthy nonsmoking controls had a mean age of 45 years, compared with their COPD cohort with a mean age of 62 years. This may have confounded their findings, because we have noted that normal younger subjects, aged < 50 years, have significantly lower values for CANO compared with older normals, aged > 60 years.37,38 However, in a subsequent study, Brindicci et al7 reported increased messenger RNA expression and activity of isoenzyme nNOS in peripheral lung tissue that reflected the severity of the disease. Although Högman at al107 used age-matched controls, neither Högman et al107 nor Brindicci et al12 corrected for axial back-diffusion of NO from large airways to peripheral lung.33,34 This underestimates J’awNO and overestimates CANO. After correction, J’awNO will increase and CANO will decrease.33,34 We108 recently compared COPD patients to age-matched controls using the two-compartment model23 and, after correcting for NO axial back-diffusion,33 found normal values for J’awNO and CANO. Furthermore, we108 noted that moderate-dose, but not low-dose, ICS could suppress normal values for J’awNO. Previously, Roy et al109 noted normal J’awNO and CANO in COPD patients compared with age-matched healthy, older, nonsmoking subjects, but without correcting for NO axial back-diffusion.33 Finally, Dummer et al110 also reported FeNO at 50 mL/s, a surrogate for J’awNO, was a weak predictor of increase in FEV1 (liters) following short-term steroid response in moderate-to-severe COPD patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and 3 disease. In conclusion, in COPD, the role of FeNO monitoring is less clear and therefore less established than in asthma. Furthermore, concurrent smoking reduces FeNO, and may provide spurious results.