Exploring Exhaled Breath Analysis in Adults With Chronic Visceral Acid Sphingomyelinase Deficiency to Identify Potential Biomarkers of Pulmonary Involvement

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease. The most commonly affected organs are the spleen, the liver, and the lungs. Pulmonary involvement resembles interstitial lung disease and often leads to decreased diffusion capacity of the lungs for carbon monoxide (DLCO). An emerging technique in pulmonary research is the analysis of exhaled breath. The aim of this study was to investigate potential markers of pulmonary involvement in the exhaled breath of adult chronic visceral ASMD patients and to quantify findings on high-resolution computed tomography (HRCT) of the lungs in order to be able to correlate HRCT findings with (the potential) markers for pulmonary involvement. Fifteen adult, chronic visceral ASMD patients and 34 age-, sex-, and smoking habit-matched healthy controls were recruited and provided two different types of exhaled breath samples: exhaled air and exhaled condensate. Additionally, pulmonary function testing was performed for both patients and healthy controls, and HRCT of the lungs and biochemical markers were available for patients. Exhaled breath samples were analyzed using gas and liquid chromatography-mass spectrometry (GC–MS and LC–MS respectively). Fifteen compounds of interest were identified based on significant differences between ASMD patients and healthy controls, of which the most promising were 2-hydroperoxyhexane, 6-heptyn-2-one, and 4-pentenyl acetate. Other compounds have been described in the context of systemic sclerosis (i.e., acetophenone) or lung cancer (i.e., benzaldehyde and dodecane). Some markers were associated with the pathophysiological process of lipid peroxidation (i.e., decane, dodecane and 2-methylnonane). SPLSDA and AUROCC analyses showed that the model was better able to distinguish the patients with pulmonary involvement from their matched controls than all patients from all controls. Lastly, a quantitative HRCT score was performed and correlated with patients' DLCO (R = −0.74, p = 0.006). The most promising markers based on our analyses (i.e., 2-hydroperoxyhexane, 6-heptyn-2-one and 4-pentenyl acetate) have not been described in previous studies in the pulmonary field and might be ASMD-specific.