Lung diffusing capacity for nitric oxide and carbon monoxide in relation to morphological changes as assessed by computed tomography in patients with cystic fibrosis.

BACKGROUND: Due to large-scale destruction, changes in membrane diffusion (Dm) may occur in cystic fibrosis (CF), in correspondence to alterations observed by computed tomography (CT). Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO), as opposed to the conventional diffusing capacity for carbon monoxide (DLCO). We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. METHODS: Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean +/- SD age 35 +/- 9 y, FEV1 66 +/- 28%pred). Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS) with z-scores of functional measures were computed. RESULTS: CT scores correlated best with DLNO (rS = -0.83; p < 0.001). Scores were also related to the volume-specific NO transfer coefficient (KNO; rS = -0.63; p < 0.01) and to DLCO (rS = -0.79; p < 0.001) but not KCO. Z-scores for DLNO were significantly lower than for DLCO (p < 0.001). Correlations with spirometric (e.g., FEV1, IVC) or bodyplethysmographic (e.g., SRaw, RV/TLC) indices were weaker than for DLNO or DLCO but most of them were also significant (p < 0.05 each). CONCLUSION: In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF.

Lung diffusing capacity for nitric oxide and carbon monoxide: dependence on breath-hold time.

BACKGROUND: The combined measurement of diffusing capacity of the lung for nitric oxide (Dlno) and diffusing capacity of the lung for carbon monoxide (Dlco) is a simple, noninvasive tool, but methodologic factors might influence results and reproducibility. We thus quantified the influence of breath-hold time on Dlco and Dlno in subjects with or without airway disease. METHODS: Simultaneous single-breath measurements of Dlco and Dlno were performed in 10 patients with cystic fibrosis (CF) [mean +/- SD age, 33 +/- 9 years; FEV(1), 69 +/- 28% of predicted] and 10 healthy subjects (age, 31 +/- 9 years; FEV(1), 108 +/- 8% of predicted), using the Masterscreen PFT (Viasys/Jaeger; Höchberg, Germany), with 45 ppm of inspired nitric oxide (NO), and breath-hold times of 4 s, 6 s, 8 s, and 10 s. The last two of three consecutive measurements were used for analysis. RESULTS: In healthy subjects but not patients with CF, Dlno, and Dlco differed significantly (p < 0.05 each) between breath-hold times. Differences primarily occurred at 4 s and 10 s, while at 6 s and 8 s alveolar volume (VA), Dlno, Dlco, and Dlno/Dlco were similar. Variability of consecutive measurements (either three or the last two measurements) did not depend on breath-hold time. At 8 s, mean variabilities of Dlno and Dlco in healthy subjects were 4.9% and 2.5%, respectively, and 4.2% and 3.2% at 6 s. At 8 s, mean variabilities of Dlno and Dlco in CF patients were 4.4% and 1.9%, and 7.4% and 3.3% at 6 s. CONCLUSIONS: Single-breath determinations of dlno and dlco showed no difference between breath-hold times of 6 s and 8 s in subjects with or without airway obstruction, and reproducibility was acceptable. Standardization of breath-hold time for Dlno measurements seems important for clinical and research comparisons.