We measured diffusing capacity (DLCO), alveolar membrane properties (D (m)), capillary lung volume (V (c)), and alveolar volume (V (A) ) in 20 healthy subjects (12 males; age 32.4 +/- 13 (SD); BMI 21.7 +/- 3; non smokers) at total lung capacity (TLC) and at approximately 80, 60, and 40% TLC. In all subjects, D (m) increased with lung volume, the increase being significantly greater for higher values of D (m)(TLC): the inter-individual differences can be interpreted by a greater number of alveolar units coupled to a lower thickness of the air-blood barrier (thus a higher alveolar surface to thickness ratio S (A)/tau). On the average, the volume-dependent increase of D (m) from approximately 40 to 100% TLC is less than expected based on geometrical increase of S (A) /tau. In fact, up to approximately 80% TLC, the increase in D (m) closely reflects only the increase of S (A), suggesting "unfolding" of the septa with no appreciable decrease in tau. Conversely, above 80% TLC, the decrease in tau due to parenchymal stretching becomes the main factor affecting D (m). In all subjects, V (c) decreased with increasing lung volume, in line with an increase in parenchymal stretching; the decrease was significantly larger for higher values of V (c) (40% TLC). Possibly reflecting differences in alveolar capillary density. No correlation was found between D (m)(TLC) and V (c)(40%TLC). The individual specificity in the lung volume dependence of V (c) and D (m) can be reasonably described by evaluating the V (c)/D (m) ratio at TLC and at approximately 40%TLC.

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