Intersession variability in single-breath diffusing capacity in diabetics without overt lung disease

Rationale American Thoracic Society guidelines state that a 10% or greater intersession change in diffusing capacity of the lung (DLCO) should be considered clinically significant. However, little is known about the short-term intersession variability in DLCO in untrained subjects or how variability is affected by rigorous external quality control. Objectives: To characterize the intersession variability of DLCO and the effect of different quality control methods in untrained individuals without significant lung disease. Methods: Data were pooled from the comparator arms of 14 preregistration trials of inhaled insulin that included nonsmoking diabetic patients without significant lung disease. A total of 699 participants performed repeated DLCO measurements using a highly standardized technique. A total of 948 participants performed repeated measurements using routine clinical testing. Measurements and Main Results: The mean intersession absolute change in DLCO using the highly standardized method was 1.45 ml/ minute/mm Hg (5.64%) compared with 2.49 ml/minute/mm Hg (9.52%) in the routine testing group (P < 0.0001 for both absolute and percent difference). The variability in absolute intersession change in DLCO increased with increasing baseline DLCO values, whereas the absolute percentage of intersession change was stable across baseline values. Depending on the method, 15.5 to 35.5% of participants had an intersession change of 10% or greater. A 20% or greater threshold would reduce this percentage of patients to 1 to 10%. Conclusions: Intersession variability in DLCO measurement is dependent on the method of testing used and baseline DLCO. Using a more liberal threshold to define meaningful intersession change may reducethe misclassificationof normal variation as abnormal change.