Longitudinal pulmonary function testing outcome measures in Duchenne muscular dystrophy: long-term natural history with and without glucocorticoids

Background Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness and respiratory decline. To date, studies have focused on respiratory decline and loss of ambulation as a metric of loss of skeletal muscle strength. However, new functional measures can assess skeletal muscle disease regardless of ambulatory status. The relationship between these tests and concurrent lung function is currently unexplored. Objective To assess the correlation between spirometry measurements and functional muscle assessments such as accelerometry and quantitative muscle testing (QMT). Methods Enrolled patients with DMD underwent accelerometry and QMT at study clinic visits. Any pulmonary function testing within 6 months of visit was obtained from the electronic medical record. The Spearman correlation coefficient was used to assess the relationship between spirometry and functional muscle testing. Results Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) demonstrated the strongest correlation with accelerometry. Both FVC and FEV1 showed a similar relationship to accelerometry when activity was divided into intensity categories, with low intensity and moderate‐to‐vigorous activity categories showing the strongest correlation. Maximal expiratory pressure (MEP) and FVC showed the most robust correlations with total QMT (p < 0.001 and p < 0.01, respectively). Conclusion Lung function, specifically FVC percent predicted and FEV1%p, shows a good correlation with upper and lower extremity skeletal muscle functional testing such as accelerometry and QMT.

Section: Discussionsupporting

confidence: 89%

Spirometry correlates with physical activity in patients with Duchenne muscular dystrophy

Kaslow

Sokolow

Donnelly

et al. 2023

“…55 Finally, in the group A patients, percent predicted FVC declined progressively and smoothly over time, at a mean rate of 2.7% per year before reaching a very low plateau. This pattern of pulmonary function is consistent with a pulmonary phenotype, 56 and argues against an environmental cause for the poor pulmonary function seen in the group A subjects. To help exclude nonphenotypic causes of the poor heart function in group B, the authors reviewed the patients' records for use of cardiac medications and for illnesses that might have selectively affected heart function.…”

Section: Identification Of Congenital Lung Malformations (Clms) Hassupporting

confidence: 81%

Pediatric Pulmonology Year in Review 2018: Rare lung disease, neuromuscular disease, and diagnostic testing

Gower

Birnkrant

Black

et al. 2019

Pediatric Pulmonology publishes original research, case reports, and review articles on topics related to a wide range of children's respiratory disorders. In this article, we highlight the past year's publications in the topic areas of rare lung diseases, respiratory complications of neuromuscular disorders, and diagnostic testing, as well as selected literature in these areas from other journals.

“…We have identified 19 studies fulfilling our selection criteria [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] ( Figure 1): nine studies exploring the effect of steroids on pulmonary function, [17][18][19][20][21][22][23][24][25] six studies exploring the effect of idebenone (one study explored the effect of both steroids and idebenone), 19,[26][27][28][29][30] three studies about eteplirsen, [31][32][33] one study about ataluren, 34 and one study about stem-cell therapy 35 (Tables 1-3).…”

Section: Therapeutic Agents Investigatedmentioning

confidence: 99%

“…With regard to study design, 5 of 19 original research papers were retrospective studies 18,[22][23][24][25] and 13 were prospective studies, including six randomized controlled trials, 19,[26][27][28][29][30] four prospective studies with no control group, 20,21,34,35 three randomized controlled trials followed by an open-label phase, [31][32][33] and one prospective cohort study including a treatment and a nontreatment group. 17 It is noteworthy that in three studies the control group was a natural history cohort or a historical control group. [31][32][33] All studies regarding idebenone were randomized trials, whereas 5 of 9 studies about steroids were retrospective.…”

Section: Types Of Research Studiesmentioning

confidence: 99%

“…It is evident from the results (Table 1) that the administration of steroids exerts a beneficial effect on lung function, as reflected by spirometry, as well as by clinical outcomes. The principal clinical effect of steroids administration is deceleration (rather than reversal) of pulmonary disease progression, as reflected by spirometry.According to the study by McDonald et al17 this benefit seems to be greater in younger age groups. On the contrary, FVC does ultimately decline in the older age groups and falls to clinically hazardous levels.…”

mentioning

confidence: 94%

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Therapies that are available and under development for Duchenne muscular dystrophy: What about lung function?

Γώγου

Pavlou

Haidopoulou

2019

Background Respiratory failure is the principal source of morbidity and mortality among patients with Duchenne muscular dystrophy exerting a negative influence on their total quality of life. The aim of this review is to provide systematically current literature evidence about the effects of different treatment options (available or under development) for Duchenne muscular dystrophy on the pulmonary function of these patients. Methods A comprehensive search was undertaken using multiple health‐related databases, while two independent reviewers assessed the eligibility of studies. A third person addressed any disagreements between reviewers. The quality of the methodology of the included studies was also assessed. Results A total of 19 original research papers (nine evaluating the role of steroids, six idebenone, three eteplirsen, one stem‐cell therapy, and one ataluren) were found to fulfill our selection criteria with the majority of them (14 of 19) being prospective studies, not always including a control group. Endpoints mainly used in these studies were values of pulmonary function tests. Current and under development treatments proved to be safe and no significant adverse events were reported. A beneficial impact on pulmonary function was described by authors in the majority of these studies. The principal effect was slowing of lung disease progress, as expressed by spirometric values. However, the risk of bias was introduced in many of the above studies, while high heterogeneity in terms of treatment protocols and outcome measures limits the comparability of the results. Conclusion Glucocorticoids remain the best‐studied pharmacologic therapy for Duchenne muscular dystrophy and very likely delay the expected decline in lung function. With regard to new therapeutic agents, initial study results are encouraging. However, larger clinical trials are needed that minimize the risk of study bias, optimize the comparability of treatment groups, examine clinically meaningful pulmonary outcome measures, and include long‐term follow up.