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

Trucco F 1 , Domingos JP 2 , Tay CG 3 , Ridout D 4 , Maresh K 2 , Munot P 2 Show all authors , Sarkozy A 2 , Robb S 2 , Quinlivan R 5 , Riley M 6 , Burch M 7 , Fenton M 7 , Wallis C 8 , Chan E 8 , Abel F 8 , Manzur AY 2 , Muntoni F 9

Affiliations 

  • 1 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
  • 2 Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, England
  • 3 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
  • 4 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
  • 5 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
  • 6 Lung Function Laboratory, Great Ormond Street Hospital, London, England
  • 7 Department of Cardiology, Great Ormond Street Hospital, London, England
  • 8 Department of Respiratory Medicine, Great Ormond Street Hospital, London, England
  • 9 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
Chest, 2020 10;158(4):1606-1616.
PMID: 32387519 DOI: 10.1016/j.chest.2020.04.043

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications