Disease monitoring using lung function trajectory in lymphangioleiomyomatosis: assessment in two national cohorts.

Study Question: In lymphangioleiomyomatosis, airflow obstruction and impairment of gas transfer progress at variable rates and serial lung function is recommended for disease monitoring. As these measurements are variable, recognising subjects needing treatment can be difficult. We used two prospective national cohorts to study change over time and variation in FEV to inform clinical decision making.

Patients And Methods: Clinical and lung function data for 141 UK and 148 American subjects were studied. Multilevel mixed effects modelling, route mean square analysis of errors and Bland-Altman analysis were used to analyse variability in lung function over time.

Results: At baseline assessment, DL was reduced to a greater degree than FEV. In untreated patients, FEV and DL declined at proportionately similar rates independent of initial lung function. In mechanistic target of rapamycin (mTOR) inhibitor treated patients, FEV stabilised but DL continued to decline. FEV/DL per cent predicted ratio was 1.37 (0.43) at baseline and increased to 1.41 (0.50) after 42 (24) months (p=0.0002). At least five measurements were required before >70% of individuals had estimates of rate of FEV loss within 50 mL/year and DL loss within 0.1 mmol/min/kPa/year of the final values.

Conclusions: While FEV and DL fall proportionately in most, in early disease and during mTOR inhibitor treatment, DL should also be monitored as it may fall independent of FEV. Since at least five observations over many months are required to make confident estimates of FEV and DL trajectories, new strategies are needed to measure disease activity and target early treatment appropriately.