Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency
Williams–Beuren syndrome (WS) results from the deletion of 25–27 coding genes, including elastin (<i>ELN</i>), on human chromosome 7q11.23. Elastin provides recoil to tissues; emphysema and chronic obstructive pulmonary disease have been linked to its destruction. Consequently, we hypoth...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/6/1438 |
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| author | Elise K. Kronquist Maninder Kaur Leah M. Gober Russell H. Knutsen Yi-Ping Fu Zu-Xi Yu Danielle R. Donahue Marcus Y. Chen Sharon Osgood Neelam Raja Mark D. Levin Amisha Barochia Beth A. Kozel |
| author_facet | Elise K. Kronquist Maninder Kaur Leah M. Gober Russell H. Knutsen Yi-Ping Fu Zu-Xi Yu Danielle R. Donahue Marcus Y. Chen Sharon Osgood Neelam Raja Mark D. Levin Amisha Barochia Beth A. Kozel |
| author_sort | Elise K. Kronquist |
| collection | DOAJ |
| description | Williams–Beuren syndrome (WS) results from the deletion of 25–27 coding genes, including elastin (<i>ELN</i>), on human chromosome 7q11.23. Elastin provides recoil to tissues; emphysema and chronic obstructive pulmonary disease have been linked to its destruction. Consequently, we hypothesized that elastin insufficiency would predispose to obstructive features. Twenty-two adults with WS (aged 18–55) and controls underwent pulmonary function testing, 6 min walk, and chest computed tomography (CT). Lung and airspace dimensions were assessed in <i>Eln<sup>+/−</sup></i> and control mice via microCT and histology. The forced expiratory volume in 1 s (FEV<sub>1</sub>) and the ratio of FEV<sub>1</sub> to forced vital capacity (FVC) were lower in adults with WS (<i>p</i> < 0.0001 and <i>p</i> < 0.05, respectively). The FEV<sub>1</sub>/FVC ratio was more frequently below the lower limit of normal in cases (<i>p</i> < 0.01). The ratio of residual volume to total lung capacity (RV/TLC, percent predicted) was higher in cases (<i>p</i> < 0.01), suggesting air trapping. People with WS showed reduced exercise capacity (<i>p</i> < 0.0001). In <i>Eln<sup>+/−</sup></i> mice, ex vivo lung volumes were increased (<i>p</i> < 0.0001), with larger airspaces (<i>p</i> < 0.001). Together these data show that elastin insufficiency impacts lung physiology in the form of increased air trapping and obstruction, suggesting a role for lung function monitoring in adults with WS. |
| first_indexed | 2024-03-10T00:00:05Z |
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| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T00:00:05Z |
| publishDate | 2022-06-01 |
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| spelling | doaj.art-22bc546de50a497e9af62410db397f9c2023-11-23T16:18:11ZengMDPI AGDiagnostics2075-44182022-06-01126143810.3390/diagnostics12061438Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin InsufficiencyElise K. Kronquist0Maninder Kaur1Leah M. Gober2Russell H. Knutsen3Yi-Ping Fu4Zu-Xi Yu5Danielle R. Donahue6Marcus Y. Chen7Sharon Osgood8Neelam Raja9Mark D. Levin10Amisha Barochia11Beth A. Kozel12National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20824, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USANational Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USAWilliams–Beuren syndrome (WS) results from the deletion of 25–27 coding genes, including elastin (<i>ELN</i>), on human chromosome 7q11.23. Elastin provides recoil to tissues; emphysema and chronic obstructive pulmonary disease have been linked to its destruction. Consequently, we hypothesized that elastin insufficiency would predispose to obstructive features. Twenty-two adults with WS (aged 18–55) and controls underwent pulmonary function testing, 6 min walk, and chest computed tomography (CT). Lung and airspace dimensions were assessed in <i>Eln<sup>+/−</sup></i> and control mice via microCT and histology. The forced expiratory volume in 1 s (FEV<sub>1</sub>) and the ratio of FEV<sub>1</sub> to forced vital capacity (FVC) were lower in adults with WS (<i>p</i> < 0.0001 and <i>p</i> < 0.05, respectively). The FEV<sub>1</sub>/FVC ratio was more frequently below the lower limit of normal in cases (<i>p</i> < 0.01). The ratio of residual volume to total lung capacity (RV/TLC, percent predicted) was higher in cases (<i>p</i> < 0.01), suggesting air trapping. People with WS showed reduced exercise capacity (<i>p</i> < 0.0001). In <i>Eln<sup>+/−</sup></i> mice, ex vivo lung volumes were increased (<i>p</i> < 0.0001), with larger airspaces (<i>p</i> < 0.001). Together these data show that elastin insufficiency impacts lung physiology in the form of increased air trapping and obstruction, suggesting a role for lung function monitoring in adults with WS.https://www.mdpi.com/2075-4418/12/6/1438Williams Beuren syndromepulmonary function testsair trappingobstructive pulmonary disease |
| spellingShingle | Elise K. Kronquist Maninder Kaur Leah M. Gober Russell H. Knutsen Yi-Ping Fu Zu-Xi Yu Danielle R. Donahue Marcus Y. Chen Sharon Osgood Neelam Raja Mark D. Levin Amisha Barochia Beth A. Kozel Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency Diagnostics Williams Beuren syndrome pulmonary function tests air trapping obstructive pulmonary disease |
| title | Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency |
| title_full | Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency |
| title_fullStr | Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency |
| title_full_unstemmed | Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency |
| title_short | Airflow Obstruction in Adults with Williams Syndrome and Mice with Elastin Insufficiency |
| title_sort | airflow obstruction in adults with williams syndrome and mice with elastin insufficiency |
| topic | Williams Beuren syndrome pulmonary function tests air trapping obstructive pulmonary disease |
| url | https://www.mdpi.com/2075-4418/12/6/1438 |
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