@article{42d38c6b7a9e4d29a2baaff349c8479a,
title = "Characterizing Expiratory Respiratory Muscle Degeneration in Duchenne Muscular Dystrophy Using MRI",
abstract = "Background: Expiratory muscle weakness and impaired airway clearance are early signs of respiratory dysfunction in Duchenne muscular dystrophy (DMD), a degenerative muscle disorder in which muscle cells are damaged and replaced by fibrofatty tissue. Little is known about expiratory muscle pathology and its relationship to cough and airway clearance capacity; however, the level of muscle replacement by fat can be estimated using MRI and expressed as a fat fraction (FF). Research Question: How does abdominal expiratory muscle fatty infiltration change over time in DMD and relate to clinical expiratory function? Study Design and Methods: Individuals with DMD underwent longitudinal MRI of the abdomen to determine FF in the internal oblique, external oblique, and rectus abdominis expiratory muscles. FF data were used to estimate a model of expiratory muscle degeneration by using nonlinear mixed effects and a cumulative distribution function. FVC, maximal inspiratory and expiratory pressures, and peak cough flow were collected as clinical correlates to MRI. Results: Forty individuals with DMD (aged 6-18 years at baseline) participated in up to five visits over 36 months. Modeling estimated the internal oblique progresses most quickly and reached 50% replacement by fat at a mean patient age of 13.0 years (external oblique, 14.0 years; rectus abdominis, 16.2 years). Corticosteroid-untreated individuals (n = 4) reached 50% muscle replacement by fat 3 to 4 years prior to treated individuals. Individuals with mild clinical dystrophic phenotypes (n = 3) reached 50% muscle replacement by fat 4 to 5 years later than corticosteroid-treated individuals. Internal and external oblique FFs near 50% were associated with maximal expiratory pressures < 60 cm H2O and peak cough flows < 270 L/min. Interpretation: These data improve understanding of the early phase of respiratory compromise in DMD, which typically presents as airway clearance dysfunction prior to the onset of hypoventilation, and links expiratory muscle fatty infiltration to pulmonary function measures.",
keywords = "Duchenne muscular dystrophy, MRI, airway clearance, cough, expiratory muscles",
author = "Barnard, {Alison M.} and Lott, {Donovan J.} and Abhinandan Batra and Triplett, {William T.} and Willcocks, {Rebecca J.} and Forbes, {Sean C.} and Rooney, {William D.} and Daniels, {Michael J.} and Smith, {Barbara K.} and Krista Vandenborne and Walter, {Glenn A.}",
note = "Funding Information: FUNDING/SUPPORT: Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [P50 AR052646 which was formerly U54 AR052646 and R01 AR056973 ]. The first author was supported by T32 HL134621 and K12 HD055929 during the conduct of this work. A portion of this work was performed in the McKnight Brain Institute at the National High Magnetic Field Laboratory{\textquoteright}s Advanced Magnetic Resonance Imaging and Spectroscopy Facility, which is supported by National Science Foundation Cooperative Agreement No. DMR-1644779 and DMR-1157490 and by the state of Florida. Funding Information: FUNDING/SUPPORT: Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [P50 AR052646 which was formerly U54 AR052646 and R01 AR056973]. The first author was supported by T32 HL134621 and K12 HD055929 during the conduct of this work. A portion of this work was performed in the McKnight Brain Institute at the National High Magnetic Field Laboratory's Advanced Magnetic Resonance Imaging and Spectroscopy Facility, which is supported by National Science Foundation Cooperative Agreement No. DMR-1644779 and DMR-1157490 and by the state of Florida.Author contributions: G. A. W. takes responsibility for the content of the manuscript, including the data and analysis. A. M. B. D. J. L. W. T. T. R. J. W. S. C. F. W. D. R. B. K. S. K. V. and G. A. W. contributed to the design and conception of the study; A. M. B. D. J. L. A. B. and G. A. W. contributed to data collection; A. M. B. W. T. T. W. D. R. M. J. D. B. K. S. and G. A. W. contributed to data analysis and interpretation; A. M. B. drafted the manuscript; and D. J. L. A. B. W. T. T. R. J. W. S. C. F. W. D. R. M. J. D. B. K. S. K. V. and G. A. W. contributed to revising it critically for important intellectual content. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: B. K. S. reports being a consultant for Sarepta Therapeutics and Amicus Therapeutics on content unrelated to the manuscript. K. V. reported funding from Italfarmaco, Sarepta Therapeutics, ML Bio Solutions, and Catabasis Pharmaceuticals via a research service agreement to the University of Florida (unrelated to the manuscript). G. A.W. received grant support from the National Institutes of Health for the submitted study. None declared (A. M. B. D. J. L. A. B. W. T. T. R. J. W. S. C. F. W. D. R. M. J. D.). Role of the sponsor: None of the funding sources had a role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript. Other contributions: The authors acknowledge Samuel Riehl, BS, for his assistance with data collection and analysis. They also acknowledge the MR technologists who assisted with MRI acquisition: Judy Steadman, RT, Christi Swiers, RT (R) (M) (MR), and Tammy Nicholson, BSRT (R) (MR). They appreciate the boys and young men who were participants in the study. Additional information: The e-Figures and e-Table can be found in the Supplemental Materials section of the online article. Funding Information: Financial/nonfinancial disclosures: The authors have reported to CHEST the following: B. K. S. reports being a consultant for Sarepta Therapeutics and Amicus Therapeutics on content unrelated to the manuscript. K. V. reported funding from Italfarmaco , Sarepta Therapeutics , ML Bio Solutions, and Catabasis Pharmaceuticals via a research service agreement to the University of Florida (unrelated to the manuscript). G. A.,W. received grant support from the National Institutes of Health for the submitted study. None declared (A. M. B., D. J. L., A. B., W. T. T., R. J. W., S. C. F., W. D. R., M. J. D.). Publisher Copyright: {\textcopyright} 2021 American College of Chest Physicians",
year = "2022",
month = mar,
doi = "10.1016/j.chest.2021.08.078",
language = "English (US)",
volume = "161",
pages = "753--763",
journal = "Diseases of the chest",
issn = "0012-3692",
publisher = "American College of Chest Physicians",
number = "3",
}