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Early NIV is associated with accelerated lung function decline in Duchenne muscular dystrophy treated with glucocorticosteroids.

ABSTRACT: BACKGROUND:Use of non-invasive ventilation (NIV) in adolescents with Duchenne muscular dystrophy (DMD) has increased with concomitant extended survival. AIM:To describe lung function (LF) changes with NIV in adolescents with DMD and to assess differences between Steroid Users and Steroid Naïve subjects. METHOD:A retrospective cohort of adolescents with DMD initiating NIV over 10 years was conducted. Serial LF before and after NIV initiation was collated. Use of systemic glucocorticosteroids, adherence to NIV and presence of cardiac disease were assessed. RESULTS:Twenty-nine men started NIV, median age 14.66 years (IQR 2.35, 10.47-17.96). Nine were Steroid Users and eight were Steroid Naïve. Indications for NIV were apnoea-hypopnoea index >5 and/or nocturnal hypoventilation. LF is better (forced vital capacity (FVC) z-score -3.26 vs -5.41, p < 0.02) and decline slower (FVC z-score -0.58?per annum (pa) vs -0.68?pa, p<0.001) in Steroid Users compared with Steroid Naïve subjects. Following NIV initiation, FVC z-score decline slowed for the whole (-0.72?pa (95%?CI -0.79 to 0.64) to -0.46?pa (95%?CI -0.54 to 0.38)?p < 0.001) and Steroid Naïve groups (-0.74 (95% CI -0.85 to 0.63) to -0.44?pa (95%?CI -0.56 to 0.32)?p < 0.001) but accelerated in the Steroid User group (-0.56 (95% CI -0.70 to 0.42) to -0.75?pa (95%?CI -0.89 to 0.61)?p < 0.001). Adherence to NIV and cardiac disease did not impact decline. CONCLUSION:Overall, LF decline is reduced on NIV. Steroid Naïve patients have lower LF and faster decline, which slows following NIV initiation. An accelerated LF decline was seen on NIV in Steroid Users which requires further prospective research.

SUBMITTER: Angliss ME

PROVIDER: S-EPMC7047482 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Early NIV is associated with accelerated lung function decline in Duchenne muscular dystrophy treated with glucocorticosteroids.

Angliss Megan E ME Sclip Kiara D KD Gauld Leanne L

BMJ open respiratory research 20200201 1

<h4>Background</h4>Use of non-invasive ventilation (NIV) in adolescents with Duchenne muscular dystrophy (DMD) has increased with concomitant extended survival.<h4>Aim</h4>To describe lung function (LF) changes with NIV in adolescents with DMD and to assess differences between <i>Steroid Users</i> and <i>Steroid Naïve</i> subjects.<h4>Method</h4>A retrospective cohort of adolescents with DMD initiating NIV over 10 years was conducted. Serial LF before and after NIV initiation was collated. Use o ...[more]

PMID: 32079608

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Project description:Dystrophinopathies cover a spectrum of rare progressive X-linked muscle diseases, arising from DMD mutations. They are among the most common pediatric muscular dystrophies, being Duchenne muscular dystrophy (DMD) the most severe form. Despite the fact that there is still no cure for these serious diseases, unprecedented advances are being made for the development of therapies for DMD. Some of which are already conditionally approved: exon skipping and premature stop codon read-through. The present work aimed to characterize the mutational spectrum of DMD in an Argentinian cohort, to identify candidates for available pharmacogenetic treatments and finally, to conduct a comparative analysis of the Latin American (LA) frequencies of mutations amenable for available DMD therapies. We studied 400 patients with clinical diagnosis of dystrophinopathy, implementing a diagnostic molecular algorithm including: MLPA/PCR/Sanger/Exome and bioinformatics. We also performed a meta-analysis of LA's metrics for DMD available therapies. The employed algorithm resulted effective for the achievement of differential diagnosis, reaching a detection rate of 97%. Because of this, corticosteroid treatment was correctly indicated and validated in 371 patients with genetic confirmation of dystrophinopathy. Also, 20 were eligible for exon skipping of exon 51, 21 for exon 53, 12 for exon 45 and another 70 for premature stop codon read-through therapy. We determined that 87.5% of DMD patients will restore the reading frame with the skipping of only one exon. Regarding nonsense variants, UGA turned out to be the most frequent premature stop codon observed (47%). According to the meta-analysis, only four LA countries (Argentina, Brazil, Colombia and Mexico) provide the complete molecular algorithm for dystrophinopathies. We observed different relations among the available targets for exon skipping in the analyzed populations, but a more even proportion of nonsense variants (∼40%). In conclusion, this manuscript describes the theragnosis carried out in Argentinian dystrophinopathy patients. The implemented molecular algorithm proved to be efficient for the achievement of differential diagnosis, which plays a crucial role in patient management, determination of the standard of care and genetic counseling. Finally, this work contributes with the international efforts to characterize the frequencies and variants in LA, pillars of drug development and theragnosis.

Dataset Information

Early NIV is associated with accelerated lung function decline in Duchenne muscular dystrophy treated with glucocorticosteroids.

Publications

Early NIV is associated with accelerated lung function decline in Duchenne muscular dystrophy treated with glucocorticosteroids.

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