Evolution of Diffusing Capacity of the Lungs for Carbon Monoxide in Lymphangioleiomyomatosis: Historical Perspectives and the Role of Advanced Imaging.

Abstract

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease affecting women and is characterized by the proliferation of abnormal smooth muscle-like cells within the lungs, kidneys, and lymphatic system. FEV₁ and diffusing capacity of the lungs for carbon monoxide (Dlco) are 2 commonly used markers for evaluating the status of LAM, although the disease may be associated predominantly with changes in only 1 of these parameters. In this special feature, we trace the historical evolution of Dlco and FEV₁ in LAM up to their current uses, beginning with their relationship in early studies with histopathologic features and imaging. We transition to the use of Dlco and FEV₁ in the context of sirolimus therapy and monitoring rates of change in lung function. Finally, we examine modern imaging methods and how these techniques have contributed to our understanding of LAM progression, with a focus on the unique and perhaps undervalued role of Dlco. The LAM histologic score, which measures the involvement of cysts and LAM cells in the lung via biopsy, relates to disease stages and aligns more with Dlco than FEV₁. The cyst score, calculated from high-resolution CT (HRCT) scans, is a measure of the lung parenchyma occupied by cysts and correlates with disease progression. Large cysts as visualized by HRCT imaging predominantly influence FEV₁, whereas smaller cysts, which impact a greater surface area of the lung and may be underestimated, tend to affect Dlco.