Exhaled nitric oxide from lung periphery is increased in COPD

Single constant flow exhaled nitric oxide (eNO) cannot distinguish between the sources of NO. The present study measured eNO at multiple expired flows (MEFeNO) to partition NO into alveolar (C-alv,C-NO) and bronchial (J(aw,NO)) fractions to investigate peripheral lung contribution to eNO in chronic obstructive lung disease (COPD). MEFeNO were made in 81 subjects including 18 nonsmokers, 16 smokers and 47 COPD patients of different severity by the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD): 0 (n=14), 1 (n=7), 2 (n=11), 3 (n=8) and 4 (n=7). COPD severity was correlated with an increased Calv,No regardless of the patient's smoking habit or current treatment. The levels of Calv,NO (in ppb) were 1.4 +/- 0.09 in nonsmokers, 2.1 +/- 0.1 in smokers categorised as GOLD stage 0 (smokers-GOLD(0)), 3.3 +/- 0.18 in GOLD(1-2) and 3.4 +/- 0.1 in GOLD(3-4). Jaw,NO levels (pL center dot s(-1)) were higher in nonsmokers than smokers-GOLD(0) (716.2 +/- 33.3 versus 464.7 +/- 41.8), GOLD3-4 (609.4 +/- 71). Diffusion of NO in the airways (D-aw,D-NO pL center dot ppb(-1)s(-1)) was higher (p < 0.05) in GOLD(3-4) than in nonsmokers (15 +/- 1.2 versus 11 +/- 0.5) and smokers-GOLD(0) (11.6 +/- 0.5). M-EFeNO measurements were reproducible, free from day-to-day and diurnal variation and were not affected by bronchodilators. In conclusion, chronic obstructive pulmonary disease is associated with elevated alveolar nitric oxide. Measurements of nitric oxide at multiple expired flows may be useful in monitoring inflammation and progression of chronic obstructive pulmonary disease, and the response to anti-inflammatory treatment.