Adv Ther. 2026 Feb 16. doi: 10.1007/s12325-025-03481-4. Online ahead of print.
ABSTRACT
INTRODUCTION: 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 (DLCO) is a common clinical endpoint; however, its clinical relevance in patients with ASMD remains unclear.
METHODS: This post hoc analysis explored the relationship between DLCO 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 DLCO was imputed for 10 records (9/68 patients), assuming an annual 1% linear decrease in DLCO. A Cox proportional hazards model was fitted using percent predicted DLCO as a time-varying predictor at < 60% and ≥ 60%.
RESULTS: 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 DLCO 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 DLCO (≥ 60%). However, the result was not statistically significant (p = 0.69) because of the limited sample size, thus warranting further prospective validation.
CONCLUSIONS: To our knowledge, this is the first analysis to explore the relationship between DLCO and mortality risk in patients with ASMD type B and type A/B. Overall, these findings underscore how DLCO affects the mortality risk in patients with ASMD.
PMID:41697516 | DOI:10.1007/s12325-025-03481-4
