Rates of change in FEV1 and DLCO as potential indicators for mTOR inhibitor therapy in premenopausal lymphangioleiomyomatosis patients

Abstract

The value of rates of change in forced expiratory volume in 1 s (FEV₁) and diffusing capacity of the lung for carbon monoxide (D_LCO) to predict disease progression, and initiation of mTOR (mechanistic target of rapamycin) inhibitor therapy has not been evaluated.In 84 premenopausal lymphangioleiomyomatosis patients, individual rates of change in FEV₁ and D_LCO and their 95% confidence intervals were used to derive subsequent lowest values of FEV₁ and D_LCO that would prompt initiation of sirolimus therapy. These treatment criteria were compared with a criterion based on FEV₁ or D_LCO ≤70% predicted. In 12 patients undergoing sirolimus therapy both methods for determining the optimal point for initiation of therapy were evaluated.27 and 35 patients who experienced greater than expected rates of change in FEV₁ and D_LCO, respectively, would have been excluded from therapy based on an FEV₁ or D_LCO >70% pred. 25 of the 84 patients were eventually treated, but only when FEV₁ or D_LCO were ≤70% pred. Applying such treatment criteria to 12 patients undergoing sirolimus therapy would have delayed treatment for many years.Premenopausal females in whom FEV₁ or D_LCO are declining at rates above the expected based on their individual rates of decline, should be considered for sirolimus therapy before the FEV₁ or D_LCO falls to ≤70% pred.

Figure 1.

Venn diagram representing the FEV₁ and DL_CO profile of 84 LAM pre-menopausal patients. Of the 84 patients, 49 and 45 respectively, had FEV₁ or DL_CO above 70 % predicted. Thirty-five patients had an FEV₁ ≤ 70 % predicted and 39 had a DL_CO ≤ 70 % predicted. Twenty-nine patients had both FEV₁ and DL_CO ≤ 70 % predicted. Twelve of the 49 patients with FEV₁> 70 % predicted and 11 of the 45 patients with DL_CO> 70 % predicted had greater than expected declines in in FEV₁ and DL_CO, respectively.