Alveolar–capillary membrane diffusion measurement by nitric oxide inhalation in heart failure

BACKGROUND: In heart failure, lung diffusion is reduced, it correlates with prognosis and exercise capacity, and it is a therapy target. DESIGN: Diffusion is measured as CO total diffusion (DL(CO)), which has two components: membrane diffusion (Dm) and capillary volume, the latter related to CO and O2 competition for hemoglobin. DL(CO) needs to be corrected for hemoglobin. Diffusion can also be measured with NO (DL(NO)), which has a very high affinity for hemoglobin, and thus, the resistance of hemoglobin being trivial, it directly represents Dm. Therefore, Dm is directly calculated from DL(NO) through a correction factor. DL(NO) has never been measured in heart failure. The study aims at determining, in heart failure, DL(NO), Dm correction factor, and whether Dm(NO) provides Dm estimates comparable to Dm(CO). METHODS: We measured DL(CO), Dm(CO) by multi-maneuver Roughton-Forster method, and DL(CO) and DL(NO) by single-breath maneuver in 50 heart failure and 50 healthy subjects. RESULTS: DL(CO) was 21.9 ± 4.8 ml/mmHg per min and 16.8 ± 5.1 in healthy subjects and heart failure subjects, respectively (p < 0.001). DL(NO) was 88.6 ± 20.5 ml/mmHg per min and 72.5 ± 22.3, respectively (p < 0.001). The correction factors to obtain Dm from DL(NO) were 2.68 (entire population), 2.63 (healthy subjects) and 2.75 (heart failure subjects). Dm(CO) and Dm(NO) were 34.7 ± 10.9 ml/mmHg per min and 33.8 ± 7.6 in healthy subjects and 25.9 ± 2.0 and 26.4 ± 8.1 in heart failure subjects. CONCLUSIONS: DL(NO) and Dm(NO) measurements are feasible in heart failure. Dm(CO) and Dm(NO) provide comparable results. The correction factor to calculate Dm from DL(NO) in heart failure is 2.75, which is little different from the 2.63 value we observed in healthy subjects.