D23-05 Menstrual Cycle Related Respiratory Symptom Variability Defines a Distinct Phenotype in Lymphangioleiomyomatosis

Abstract Rationale Lymphangioleiomyomatosis (LAM) is a rare diffuse cystic lung disease primarily seen in women. Approximately 25-30% of women with LAM endorse cyclical worsening of their respiratory symptoms coinciding with the hormonal fluxes of a menstrual cycle. We have previously shown that women with LAM who endorse menstrual cycle related respiratory symptom variability (MCRV) tend to get diagnosed early and have more symptoms compared to women with LAM without MCRV. We conducted the menstrual variation in LAM (MVL) study to determine if patient-reported MCRV is associated with measurable cyclical spirometric changes, faster disease progression (in untreated patients), and differential treatment response to sirolimus in women with LAM. Methods After obtaining informed consent, premenopausal adult women with LAM were enrolled into the study and stratified based on self-reported MCRV and sirolimus use to yield the following four groups: 1) +MCRV/-sirolimus, 2) -MCRV/-sirolimus, 3) +MCRV/+sirolimus, and 4) -MCRV/+sirolimus. Participants were provided a handheld home spirometer and instructed to perform three spirometric measures at least twice weekly for at least six menstrual cycles to capture longitudinal changes in forced expiratory volume in one-second (FEV₁) and forced vital capacity (FVC). In addition, the timing of menstruation and ovulation as well as respiratory symptoms and health-related quality of life were concurrently tracked throughout the study duration. Mixed linear regression models were used to generate annualized FEV₁ and FVC slopes (mL/year) for each group. Results A total of 53 women with LAM were enrolled in the study to yield the following 4 subgroups: 17 +MCRV/-sirolimus, 8 -MCRV/-sirolimus, 15 +MCRV/+sirolimus, and 13 -MCRV/+sirolimus. Although not statistically significant, in the untreated group, patients with MCRV tended to decline faster compared to the patients without MCRV (FEV₁ slope of -174.501 ± 558.5 ml/year in the MCRV group vs. 40.6 ± 834.5 ml/year in the no MCRV group, p value 0.17). In the treated group, patients with MCRV tended to respond better to sirolimus treatment compared to patients without MCRV (FEV₁ slope -24.4 ± 813.6 ml/year in the MCRV group vs -121.3 ± 814.2 ml/year in the no MCRV group, p value 0.98). Conclusions Patient reported MCRV is a novel, easy-to-obtain, prognostic and predictive clinical assessment measure that might represent a distinct LAM phenotype. Routine assessment of MCRV status could help guide clinical decision making in LAM and might assist in cohort enrichment for future LAM trials. This abstract is funded by: None