{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:00:44Z","timestamp":1785301244683,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100013927","name":"National MPS Society","doi-asserted-by":"publisher","award":["1673"],"award-info":[{"award-number":["1673"]}],"id":[{"id":"10.13039\/100013927","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Almost all patients with mucopolysaccharidosis (MPS) develop respiratory dysfunction of varying severity during disease progression. While respiratory disease in MPS has traditionally been attributed to upper airway obstruction caused by glycosaminoglycan (GAG) accumulation in the trachea and bronchi, involvement of the intrapulmonary conducting airways and lung parenchyma remains poorly defined. Here, we characterised lung disease in a mouse model of MPS I using a combination of non\u2010invasive X\u2010ray Velocimetry (XV) functional lung imaging and gold\u2010standard flexiVent respiratory mechanics testing, complemented by lung volume measurements and histological analysis. XV provides regional ventilation information across the entire lung during tidal breathing. MPS I mice demonstrated reduced mean specific ventilation (the average regional expansion of lung tissue across the respiratory cycle), driven predominantly by reduced ventilation in the inner (mediastinal\u2010adjacent) lung regions, with evidence of spatially heterogeneous ventilation distribution. Lung mechanics testing showed increased conducting airway resistance, increased respiratory system compliance and reduced tissue elastance, consistent with impaired elastic recoil and expiratory flow limitation. Lung volume analysis revealed reduced opening pressure following degassing together with increased residual volume, functional residual capacity and vital capacity. Histological analysis demonstrated heterogeneous parenchymal architecture with regions of enlarged airspaces. Together, these findings demonstrate that respiratory dysfunction in MPS I is not limited to upper airway obstruction but also involves intrinsic abnormalities of the intrapulmonary conducting airways and lung parenchyma. This intrinsic pulmonary pathology likely contributes to obstructive lung disease and may underlie the susceptibility to respiratory failure observed in patients with MPS I.<\/jats:p>","DOI":"10.1002\/jimd.70219","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:23:44Z","timestamp":1782894224000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Upper Airway Involvement: Evidence of Intrinsic Lung Disease in a Mouse Model of Mucopolysaccharidosis I"],"prefix":"10.1002","volume":"49","author":[{"given":"Martin","family":"Donnelley","sequence":"first","affiliation":[{"name":"Robinson Research Institute Adelaide University  Adelaide South Australia"},{"name":"School of Medicine, College of Health Adelaide University  Adelaide South Australia"},{"name":"Respiratory and Sleep Medicine, Women's and Children's Hospital  Adelaide South 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Adelaide University  Adelaide South Australia"},{"name":"School of Medicine, College of Health Adelaide University  Adelaide South Australia"},{"name":"Respiratory and Sleep Medicine, Women's and Children's Hospital  Adelaide South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piraveen","family":"Pirakalathanan","sequence":"additional","affiliation":[{"name":"4DMedical  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4001-1674","authenticated-orcid":false,"given":"Nina","family":"Eikelis","sequence":"additional","affiliation":[{"name":"4DMedical  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"Nilsen","sequence":"additional","affiliation":[{"name":"4DMedical  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie","family":"Louise","sequence":"additional","affiliation":[{"name":"Biostatistics Unit South Australian Health and Medical Research Institute  Adelaide South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Barratt","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Health Adelaide University  Adelaide South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4046-6908","authenticated-orcid":false,"given":"Jessica","family":"Logan","sequence":"additional","affiliation":[{"name":"Mechanisms in Cell Biology and Disease Research Concentration, School of Pharmacy and Biomedical Sciences, College of Health Adelaide University  Adelaide South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Ung","sequence":"additional","affiliation":[{"name":"Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Biomedical Sciences College of Health Adelaide University  Adelaide South 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