Intercession 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 (DL_co) should be considered clinically significant. However, little is known about the short-term intersession variability in DL_co in untrained subjects or how variability is affected by rigorous external quality control. Objectives:Tocharacterize the intersession variability of DL_CO andthe effect of different quality control methods in untrained individuals without significant lung disease. Methods: Data were pooled from the comparator arms of 14 pre-registration trials of inhaled insulin that included nonsmoking diabetic patients without significant lung disease. A total of 699 participants performed repeated DL_CO 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 DL_CO 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 DL_CO increased with increasing baseline DL_CO values, whereas the absolute percentage of intersession change was stable across baseline values. Depending on the method, 15.5 to 35.5% of participants hadanintersession changeof10% orgreater.A20% or greater threshold would reduce this percentage of patients to 1 to 10%. Conclusions: Intersession variability in DL_CO measurement is dependent on the methodof testing used and baseline DL_CO. Using amore liberal threshold to define meaningful intersession change may reduce the misclassification of normal variation as abnormal change.