Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy: A Single-Site Retrospective Longitudinal Study.


Journal

Chest
ISSN: 1931-3543
Titre abrégé: Chest
Pays: United States
ID NLM: 0231335

Informations de publication

Date de publication:
10 2020
Historique:
received: 02 12 2019
revised: 29 03 2020
accepted: 01 04 2020
pubmed: 11 5 2020
medline: 4 6 2021
entrez: 11 5 2020
Statut: ppublish

Résumé

Corticosteroids (CSs) have prolonged survival and respiratory function in boys with Duchenne muscular dystrophy (DMD) when compared with CSs-naïve boys. The differential impact of frequently used CSs and their regimens on long-term (> 5 years) cardiorespiratory progression in children with DMD is unknown. This was a retrospective longitudinal study including children with DMD followed at Dubowitz Neuromuscular Centre, Great Ormond Street Hospital London, England, from May 2000 to June 2017. Patients enrolled in any interventional clinical trials were excluded. We collected patients' anthropometrics and respiratory (FVC, FVC % predicted and absolute FVC, and noninvasive ventilation requirement [NIV]) and cardiac (left ventricular shortening function [LVFS%]) function. CSs-naïve patients had never received CSs. Patients who were treated with CSs took either deflazacort or prednisolone, daily or intermittently (10 days on/10 days off) for > 1 month. Average longitudinal models were fitted for yearly respiratory (FVC % predicted) and cardiac (LVFS%) progression. A time-to-event analysis to FVC % predicted < 50%, NIV start, and cardiomyopathy (LVFS% < 28%) was performed in CS-treated (daily and intermittent) vs CS-naïve patients. There were 270 patients, with a mean age at baseline of 6.2 ± 2.3 years. The median follow-up time was 5.6 ± 3.5 years. At baseline, 263 patients were ambulant. Sixty-six patients were treated with CSs daily, 182 patients underwent CSs intermittent > 60% treatment, and 22 were CS-naïve patients. Yearly FVC % predicted declined similarly from 9 years (5.9% and 6.9% per year, respectively; P = .27) in the CSs-daily and CSs-intermittent groups. The CSs-daily group declined from a higher FVC % predicted than the CSs-intermittent group (P < .05), and both reached FVC % predicted < 50% and NIV requirement at a similar age, > 2 years later than the CS-naïve group. LVFS% declined by 0.53% per year in the CSs-treated group irrespective of the CSs regimen, significantly slower (P < .01) than the CSs-naïve group progressing by 1.17% per year. The age at cardiomyopathy was 16.6 years in the CSs-treated group (P < .05) irrespective of regimen and 13.9 years in the CSs-naïve group. CSs irrespective of the regimen significantly improved respiratory function and delayed NIV requirement and cardiomyopathy.

Sections du résumé

BACKGROUND
Corticosteroids (CSs) have prolonged survival and respiratory function in boys with Duchenne muscular dystrophy (DMD) when compared with CSs-naïve boys.
RESEARCH QUESTION
The differential impact of frequently used CSs and their regimens on long-term (> 5 years) cardiorespiratory progression in children with DMD is unknown.
STUDY DESIGN AND METHODS
This was a retrospective longitudinal study including children with DMD followed at Dubowitz Neuromuscular Centre, Great Ormond Street Hospital London, England, from May 2000 to June 2017. Patients enrolled in any interventional clinical trials were excluded. We collected patients' anthropometrics and respiratory (FVC, FVC % predicted and absolute FVC, and noninvasive ventilation requirement [NIV]) and cardiac (left ventricular shortening function [LVFS%]) function. CSs-naïve patients had never received CSs. Patients who were treated with CSs took either deflazacort or prednisolone, daily or intermittently (10 days on/10 days off) for > 1 month. Average longitudinal models were fitted for yearly respiratory (FVC % predicted) and cardiac (LVFS%) progression. A time-to-event analysis to FVC % predicted < 50%, NIV start, and cardiomyopathy (LVFS% < 28%) was performed in CS-treated (daily and intermittent) vs CS-naïve patients.
RESULTS
There were 270 patients, with a mean age at baseline of 6.2 ± 2.3 years. The median follow-up time was 5.6 ± 3.5 years. At baseline, 263 patients were ambulant. Sixty-six patients were treated with CSs daily, 182 patients underwent CSs intermittent > 60% treatment, and 22 were CS-naïve patients. Yearly FVC % predicted declined similarly from 9 years (5.9% and 6.9% per year, respectively; P = .27) in the CSs-daily and CSs-intermittent groups. The CSs-daily group declined from a higher FVC % predicted than the CSs-intermittent group (P < .05), and both reached FVC % predicted < 50% and NIV requirement at a similar age, > 2 years later than the CS-naïve group. LVFS% declined by 0.53% per year in the CSs-treated group irrespective of the CSs regimen, significantly slower (P < .01) than the CSs-naïve group progressing by 1.17% per year. The age at cardiomyopathy was 16.6 years in the CSs-treated group (P < .05) irrespective of regimen and 13.9 years in the CSs-naïve group.
INTERPRETATION
CSs irrespective of the regimen significantly improved respiratory function and delayed NIV requirement and cardiomyopathy.

Identifiants

pubmed: 32387519
pii: S0012-3692(20)30869-2
doi: 10.1016/j.chest.2020.04.043
pii:
doi:

Substances chimiques

Glucocorticoids 0
Prednisolone 9PHQ9Y1OLM

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1606-1616

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Auteurs

Federica Trucco (F)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Care, University of Genoa, Genoa, Italy.

Joana P Domingos (JP)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England.

Chee Geap Tay (CG)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England; Department of Paediatrics, University of Malaya, Kuala Lumpur, Malaysia.

Deborah Ridout (D)

Population, Policy and Practice Research and Teaching Department, UCL GOS Institute of Child Health, London, England; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, London, England.

Kate Maresh (K)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England.

Pinki Munot (P)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England.

Anna Sarkozy (A)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England.

Stephanie Robb (S)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England.

Rosaline Quinlivan (R)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England; MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery, London, England.

Mollie Riley (M)

Lung Function Laboratory, Great Ormond Street Hospital, London, England.

Michael Burch (M)

Department of Cardiology, Great Ormond Street Hospital, London, England.

Matthew Fenton (M)

Department of Cardiology, Great Ormond Street Hospital, London, England.

Colin Wallis (C)

Department of Respiratory Medicine, Great Ormond Street Hospital, London, England.

Elaine Chan (E)

Department of Respiratory Medicine, Great Ormond Street Hospital, London, England.

Francois Abel (F)

Department of Respiratory Medicine, Great Ormond Street Hospital, London, England.

Adnan Y Manzur (AY)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England.

Francesco Muntoni (F)

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England; NIHR Great Ormond Street Hospital Biomedical Research Centre, Great Ormond Street Institute of Child Health, University College London, & Great Ormond Street Hospital Trust, London, England. Electronic address: f.muntoni@ucl.ac.uk.

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Classifications MeSH