Respiratory muscle decline in duchenne muscular dystrophy

Khirani, Sonia; Ramirez, Adriana; Aubertin, Guillaume; Boulé, Michèle; Chemouny, Chrystelle; Forin, V.; Fauroux, Brigitte

doi:10.1002/ppul.22847

Cited by 109 publications

(128 citation statements)

References 46 publications

(53 reference statements)

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“…Pulmonary function data were not available for the matched historical control patients, and therefore comparison can only be made to published natural history. Pulmonary function data from recent natural history studies in patients with DMD suggest that %pMEP and %pMIP decline at a rate of 4% per year for patients in the age range of 6 to 19 years, and %pFVC declines at a rate of 5% per year for patients in the age range of 5 to 24 years 3, 31. Thus, over a period of 36 months, patients not receiving eteplirsen might be expected to show declines in MEP and MIP of approximately 11.5% and declines in FVC of approximately 14.3%.…”

Section: Resultsmentioning

confidence: 99%

“…The importance of respiratory abnormalities is well understood in later stages of DMD, but early subclinical deterioration of respiratory muscles with a mean annual decline in %pMIP and %pMEP of approximately 4% and %pFVC of approximately 5% has only recently been recognized 3, 31. %pMIP and %pMEP assess progression of DMD regardless of ambulatory status and are the most sensitive indicators of decreasing respiratory muscle strength, with %pMEP being the first pulmonary parameter to decline in patients with DMD 39, 40.…”

Section: Discussionmentioning

confidence: 99%

“…Because long‐term matched patient‐level natural history data were not available, eteplirsen‐treated patients were compared to published data31, 32 in a DMD population.…”

mentioning

confidence: 99%

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Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Mendell

Goemans²,

Lowes

et al. 2016

Annals of Neurology

445

392

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ObjectiveTo continue evaluation of the long‐term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three‐year progression of eteplirsen‐treated patients was compared to matched historical controls (HC).MethodsAmbulatory DMD patients who were ≥7 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open‐label basis. The primary functional assessment in this study was the 6‐Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype.ResultsAt 36 months, eteplirsen‐treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen‐treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.InterpretationOver 3 years of follow‐up, eteplirsen‐treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC. Ann Neurol 2016;79:257–271

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Mendell

Goemans²,

Lowes

et al. 2016

Annals of Neurology

445

392

View full text Add to dashboard Cite

show abstract

“…To this end, a number of measures are used, including lung volume recruitment, cough-assisted devices, ventilation techniques and pharmacological therapy [11][12][13]. This latter was based, until some years ago, on glucocorticoids [5,6]; however, not all patients respond to these medications, which are also associated with relevant side effects [14].…”

Section: Discussionmentioning

confidence: 99%

Measurement of Respiratory Function Decline in Patients with Duchenne Muscular Dystrophy: A Conjoint Analysis

Ripamonti¹

2018

Neurodegener. Dis. Manag.

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Summary points• In Duchenne muscular dystrophy (DMD), little attention has been paid to severity of respiratory function decline (RFD) based on disease progression.• We performed a conjoint analysis among 123 Italian clinicians to generate a scale for RFD in DMD patients.• Before the interview, 11 attributes were selected by discussion among experts. 32 'patient profiles' were generated. Each physician assessed the severity of RFD for each profile. Each level/attribute was assigned an estimated usefulness to understand its impact on RFD.• The identified attributes were forced vital capacity, forced vital capacity decline, dysphagia, type of ventilation and peak cough flow.• These results allowed the development of a scale for RFD severity.• This scale can stratify DMD patients according to the severity of their RFD.• Further validation in a larger, international sample of physicians, including expert pneumologists, by another robust approach such as a multidisciplinary Delphi panel and/or web-based collection of consensus appears necessary.• This score must be correlated with clinical findings and compared with standard testing based on guidelines, in order to correlate the perceived decline and its quantitative evaluation. • This will help define clinical approach in line with the severity of pulmonary function evaluated by our score and allow early management of DMD patients. Aim:In Duchenne muscular dystrophy (DMD), little attention has been paid to severity of respiratory function decline (RFD) based on disease progression. We performed a conjoint analysis among 123 Italian clinicians to generate a scale for RFD in DMD patients. Methods: Before the interview, 11 attributes were selected by discussion among experts. 32 'patient profiles' were generated. Each physician assessed the severity of RFD for each profile. Each level/attribute was assigned an estimated usefulness to understand its impact on RFD. Results: The identified attributes were forced vital capacity, forced vital capacity decline, dysphagia, type of ventilation and peak cough flow. These results allowed the development of a scale for RFD severity. Conclusion: This scale can stratify DMD patients according to the severity of their RFD.

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“…In non-injured subjects, these muscles are also used during forced expiratory maneuvers like a cough. Weak or paralyzed abdominal muscles results in a weak or an inadequate cough, leading to impaired secretion clearance, atelectasis, pneumonia and other respiratory complications (Fauroux et al, 2015;Inal-Ince et al, 2009;Khirani et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Trunk and respiratory motor control in typically developing children and its implications in children with chronic spinal cord injury.

Singh¹

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Singh, Goutam, "Trunk and respiratory motor control in typically developing children and its implications in children with chronic spinal cord injury." (2017 Independent sitting is a major milestone and is also a prerequisite for optimal performance of activities of daily living (ADLs). Development of sitting posture control is a dynamic process involving control of degrees of freedom of head and trunk. Traditionally, trunk has been modeled as a single unit (segment).However, recent studies have suggested that it is made up multiple spinal units, controlled by a combination of trunk muscles. During typical development, posture control of trunk is different for different trunk segments. This motor development of trunk control is a complex process due to constant interaction between the nervous system and environment. Any interruption in the normal processes would further complicate it, affecting the typical development of the child.Poor trunk control and respiratory complications are characteristic features among children, adolescents, and adults with neuromuscular disorders.vi Pediatric spinal cord injuries (SCIs) also pose a unique challenge compared to SCI in adults because of the continuous physical and cognitive development.Children with SCI exhibit deficits in trunk motor control, which impair their ability to sit or ambulate. These motor deficits can lead to compensatory changes in other segments of the body, which cause further deviations from typical postures.Trunk muscles have the dual function of supporting both, breathing and trunk posture. Therefore, in children with SCI, impairment of posture control will also affect respiratory functions. Depending on level and severity of injury, can potentially lead to severe respiratory insufficiency. Symptoms of respiratory insufficiency are highly correlated with the level and severity of spinal lesions.Injury at higher cervical and thoracic cord levels causes paresis and paralysis of most of the respiratory muscles, which increase the workload of breathing. As a result, respiratory complications are the leading cause of death among children with SCI. Therefore, impairment of posture control following SCI also affects respiratory functions.Lack of appropriate tools to evaluate trunk motor control following SCI restricts the ability to understand its development and therefore it is a challenge to design treatments and strategies to slow down or prevent the progress of longterm effects of SCI in children. In this dissertation, we studied the postural control using a Segmental Assessment Trunk Control (SATCo) test and respiratory motor control using Respiratory Motor Control Assessment (RMCA) protocol in typically developing (TD) children and compared their results to age-matched children with SCI.vii Chapter I describes the background information about the trunk and respiratory motor control and how the injury to spinal cord impacts these motor functions. Chapter II illustrates the specific aims and hypothesis of this dissertation. Methods and protocols used to ...

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Respiratory muscle decline in duchenne muscular dystrophy

Cited by 109 publications

References 46 publications

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy

Measurement of Respiratory Function Decline in Patients with Duchenne Muscular Dystrophy: A Conjoint Analysis

Trunk and respiratory motor control in typically developing children and its implications in children with chronic spinal cord injury.

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