Impact of Diffusing Lung Capacity for Carbon Monoxide on Mortality Risk in Patients with ASMD: Insights from a Post Hoc Analysis

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder with heterogenous clinical manifestations, including interstitial lung disease (ILD). Respiratory manifestations are the leading causes of mortality in patients with ASMD type B and type A/B. In ILD, the percent predicted diffusing capacity of the lungs for carbon monoxide (DL CO ) is a common clinical endpoint; however, its clinical relevance in patients with ASMD remains unclear. This post hoc analysis explored the relationship between DL CO and mortality risk in patients with ASMD type B and type A/B. Data from a prospective natural history study (NCT02004704) and a retrospective cohort study conducted in the United States were pooled based on the eligibility criteria. Percent predicted DL CO was imputed for 10 records (9/68 patients), assuming an annual 1% linear decrease in DL CO . A Cox proportional hazards model was fitted using percent predicted DL CO as a time-varying predictor at < 60% and ≥ 60%. A total of 68 patients (prospective study, n = 40; retrospective study, n = 28) diagnosed with ASMD type B or type A/B during childhood (aged 1–12 years) with ≥ 1 DL CO measurement were included in the analysis. A total of 12 deaths were recorded. The estimated hazard ratio (95% confidence interval) was 0.77 (0.22–2.67), indicating a potential trend toward an association of lower mortality risk with higher percent predicted DL CO (≥ 60%). However, the result was not statistically significant ( p = 0.69) because of the limited sample size, thus warranting further prospective validation. To our knowledge, this is the first analysis to explore the relationship between DL CO and mortality risk in patients with ASMD type B and type A/B. Overall, these findings underscore how DL CO affects the mortality risk in patients with ASMD.