{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:47:05Z","timestamp":1785491225372,"version":"3.56.0"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T00:00:00Z","timestamp":1753574400000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    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\u2010resolution 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\u2010, sex\u2010, and smoking habit\u2010matched 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\u2010mass spectrometry (GC\u2013MS and LC\u2013MS respectively). Fifteen compounds of interest were identified based on significant differences between ASMD patients and healthy controls, of which the most promising were 2\u2010hydroperoxyhexane, 6\u2010heptyn\u20102\u2010one, and 4\u2010pentenyl 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\u2010methylnonane). 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\u2009=\u2009\u22120.74,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006). The most promising markers based on our analyses (i.e., 2\u2010hydroperoxyhexane, 6\u2010heptyn\u20102\u2010one and 4\u2010pentenyl acetate) have not been described in previous studies in the pulmonary field and might be ASMD\u2010specific.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70039","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T03:00:00Z","timestamp":1753671600000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring Exhaled Breath Analysis in Adults With Chronic Visceral Acid Sphingomyelinase Deficiency to Identify Potential Biomarkers of Pulmonary Involvement"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3662-0212","authenticated-orcid":false,"given":"Eline C. B.","family":"Eskes","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"},{"name":"Inborn Errors of Metabolism Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0242-9113","authenticated-orcid":false,"given":"Bauke V.","family":"Schomakers","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam the Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"},{"name":"Core Facility Metabolomics Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4916-2866","authenticated-orcid":false,"given":"Michel","family":"van Weeghel","sequence":"additional","affiliation":[{"name":"Inborn Errors of Metabolism Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam the Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"},{"name":"Core Facility Metabolomics Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-3745","authenticated-orcid":false,"given":"Suzanne W. J.","family":"Terheggen\u2010Lagro","sequence":"additional","affiliation":[{"name":"Emma Children's Hospital Department of Pediatric Pulmonology and Allergy Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7528-8307","authenticated-orcid":false,"given":"Lilian J.","family":"Meijboom","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam UMC, Location Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Cardiovascular Sciences Pulmonary Hypertension and Thrombosis  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0464-1078","authenticated-orcid":false,"given":"Carla E. M.","family":"Hollak","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"},{"name":"Inborn Errors of Metabolism Amsterdam Gastroenterology Endocrinology Metabolism  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-8478","authenticated-orcid":false,"given":"Paul","family":"Brinkman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8162-9684","authenticated-orcid":false,"given":"Barbara","family":"Sjouke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud UMC  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-193305000-00001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.55.2.366"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2006.06.034"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.12.008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010021\u201001842\u20100"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.06.015"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-016-9893-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/rmed.2000.0942"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2381041696"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.4"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20725"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12789"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-3016"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.03.021"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-023-02983-0"},{"key":"e_1_2_7_17_1","unstructured":"(EMA) EMA Xenpozyme 2022 https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/xenpozyme."},{"key":"e_1_2_7_18_1","unstructured":"(FDA) FaDA FDA Approves First Treatment for Acid Sphingomyelinase Deficiency a Rare Genetic Disease 2022 https:\/\/www.fda.gov\/news\u2010events\/press\u2010announcements\/fda\u2010approves\u2010first\u2010treatment\u2010acid\u2010sphingomyelinase\u2010deficiency\u2010rare\u2010genetic\u2010disease."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000978"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-021-01923-5"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-021-03333-4"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12965"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13020203"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13121197"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780050106"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00080312"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00010-2017"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.12.431"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117084"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102003\u201005\u20101612"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010014\u20109711\u2010x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0572-x"},{"key":"e_1_2_7_33_1","unstructured":"Clinicaltrials.gov Longitudinal Assessment of Adults With Severe Asthma 2011 https:\/\/clinicaltrials.gov\/study\/NCT01976767."},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.10.058"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/separations11050150"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac051437y"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101302"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-S2-S11"},{"issue":"6","key":"e_1_2_7_39_1","first-page":"285","article-title":"Optimal Calculation of RNA\u2010Seq Fold\u2010Change Values","volume":"2","author":"Warden Y\u2010CY C. 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