Clinical relevance of diffusing lung capacity for carbon monoxide (DLCO) in patients with acid sphingomyelinase disease (ASMD): a post-hoc analysis

<bold>Background:</bold> ASMD, a rare lysosomal storage disease, has a wide range of clinical manifestations, including interstitial lung disease (ILD), present in >80% of patients. Respiratory disease is a leading cause of death in ASMD. Percent (%) predicted DL_CO is a sensitive measure of reduced pulmonary function in ILD, but its clinical relevance in ASMD patients remains unclear. <bold>Objective:</bold> This post-hoc analysis evaluated the relationship between DL_CO and mortality risk in patients with ASMD type B and type A/B using pooled data from a prospective natural history study and retrospective cohort studies of ASMD patients. <bold>Methods:</bold> Medical records of 68 patients with ASMD type B or type A/B (age of diagnosis: 1–12 years) and with ≥1 DL_CO measurement were pooled from the prospective (n=40) and retrospective (n=28) studies; % predicted DL_CO were imputed for 10 records (9/68 patients), assuming a linear decrease of 1% annually. A Cox proportional hazards model was fitted using DL_CO in two categories (DL_CO<60% and ≥60%) as a time-varying predictor (symptomatic respiratory manifestations are prominent at DL_CO<60%). <bold>Results:</bold> A hazard ratio [95% confidence interval] of 0.77 [0.22–2.67] was estimated indicating a lower mortality risk associated with higher % predicted DL_CO category (DL_CO ≥60 [less severe]) vs lower % predicted DL_CO category (DL_CO <60 [more severe]), but the result was not statistically significant (p=0.69) likely due to the small sample size. <bold>Conclusion:</bold> Mortality risk was higher in patients with lower % predicted DL_CO, showing how DL_CO affects overall survival in ASMD; prospective validation is warranted to confirm these findings.