Validation of the Lower Limit of Normal Diffusing Capacity for Detecting Emphysema

Abstract

Background: Diffusing capacity for carbon monoxide (D_Lco) has been regarded as reliable for detecting emphysema. The lower 5th percentile of the reference population has been used as the lower limit of normal (LLN) for D_Lco, without clinical validation. Objectives: We performed this study to validate the LLN for D_Lco and to determine the optimum cutoff LLN value for detecting emphysema. Methods: A total of 197 COPD patients and 103 healthy adult subjects were included. COPD patients with emphysema were defined as COPD patients in whom volumetric CT showed that the volume fraction of the lung at less than –950 Hounsfield units at full inspiration was more than 15%. All other COPD patients were defined as COPD patients without emphysema. All measured D_Lco values were transformed to estimates of reference population percentiles. ROC curve analysis was used to validate and to determine the optimum cutoff percentile value as the LLN for D_Lco. Results: Of the 197 COPD patients, 126 were classified as having emphysema and 71 as without emphysema. On ROC curve analysis, the lower 5th percentile used as the LLN for D_Lco had a sensitivity of 68.3% and a specificity of 98.1% to differentiate COPD patients with emphysema from healthy subjects. The lower 9th percentile was the best LLN cutoff value for detecting COPD patients with emphysema. Conclusion: The lower 5th percentile of the reference population may not be the best LLN cutoff value for D_Lco for detecting emphysema.