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Introduction <p>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&#xa0;A/B. In ILD, the percent predicted diffusing capacity of the lungs for carbon monoxide (DL<sub>CO</sub>) is a common clinical endpoint; however, its clinical relevance in patients with ASMD remains unclear.</p> Methods <p>This post hoc analysis explored the relationship between DL<sub>CO</sub> 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<sub>CO</sub> was imputed for 10 records (9/68 patients), assuming an annual 1% linear decrease in DL<sub>CO</sub>. A Cox proportional hazards model was fitted using percent predicted DL<sub>CO</sub> as a time-varying predictor at &lt; 60% and ≥ 60%.</p> Results <p>A total of 68 patients (prospective study,<i> n</i> = 40; retrospective study, <i>n</i> = 28) diagnosed with ASMD type B or type&#xa0;A/B during childhood (aged 1–12&#xa0;years) with ≥ 1 DL<sub>CO</sub> 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<sub>CO</sub> (≥ 60%). However, the result was not statistically significant (<i>p</i> = 0.69) because of the limited sample size, thus warranting further prospective validation.</p> Conclusions <p>To our knowledge, this is the first analysis to explore the relationship between DL<sub>CO</sub> and mortality risk in patients with ASMD type B and&#xa0;type A/B. Overall, these findings underscore how DL<sub>CO</sub> affects the mortality risk in patients with ASMD.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月16日

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  • Wim A. Wuyts,
  • Francesco Bonella,
  • Maurizio Scarpa,
  • Venediktos Kapetanakis,
  • Pragya Shukla,
  • Marie Fournier,
  • Maja Gasparic,
  • Ruth Pulikottil-Jacob

摘要

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.