Respiratory and upper limb function as outcome measures in ambulant and non-ambulant subjects with Duchenne muscular dystrophy: A prospective multicentre study

• Published in: Neuromuscular disorders : NMD Vol. 29; no. 4; pp. 261 - 268
• Main Authors: Ricotti, V., Selby, V., Ridout, D., Domingos, J., Decostre, V., Mayhew, A., Eagle, M., Butler, J., Guglieri, M., Van der Holst, M., Jansen, M., Verschuuren, J.J.G.M., de Groot, I.J.M., Niks, E.H., Servais, L., Straub, V., Voit, T., Hogrel, J.Y., Muntoni, F.
• Format: Journal Article Web Resource
• Language: English
• Published: England Elsevier B.V 01.04.2019
• Subjects: Adolescent; Cardiovascular & respiratory systems; Child; Child, Preschool; Composite endpoint; Duchenne muscular dystrophy; Europe; forced vital capacity; Human health sciences; Humans; Male; Mobility Limitation; Motor Activity - physiology; Muscle Strength - physiology; Muscle, Skeletal - physiopathology; Muscular Dystrophy, Duchenne - complications; Muscular Dystrophy, Duchenne - physiopathology; Neurologie; Neurology; Outcome Assessment, Health Care; peak expiratory flow; Pediatrics; Prospective Studies; pulmonary function; Pédiatrie; Respiration; Respiration Disorders - etiology; Respiration Disorders - physiopathology; Respiratory Function Tests; Sciences de la santé humaine; Systèmes cardiovasculaire & respiratoire; Upper Extremity - physiopathology; Upper limb function and strength; Europe; pulmonary function; peak expiratory flow; Composite endpoint; Upper limb function and strength; Duchenne muscular dystrophy; forced vital capacity
• ISSN: 0960-8966; 1873-2364; 1873-2364
• DOI: 10.1016/j.nmd.2019.02.002

•This study contributes to the natural history of DMD, linking the ambulant and non-ambulant phases.•Respiratory measurements, upper limb function, pinch and grip force are reported.•A composite score combining respiratory outcomes, upper limb function and strength is explored. The field of translational research in Duchenne muscular dystrophy (DMD) has been transformed in the last decade by a number of therapeutic targets, mostly studied in ambulant patients. A paucity of studies focus on measures that capture the non-ambulant stage of the disease, and the transition between the ambulant and non-ambulant phase. In this prospective natural history study, we report the results of a comprehensive assessment of respiratory, upper limb function and upper limb muscle strength in a group of 89 DMD boys followed in 3 European countries, 81 receiving corticosteroids, spanning a wide age range (5–18 years) and functional abilities, from ambulant (n = 60) to non-ambulant (n = 29). Respiratory decline could be detected in the early ambulatory phase using Peak Expiratory Flow percentage predicted (PEF%), despite glucocorticoid use (mean annual decline: 4.08, 95% CI [−7.44,−0.72], p = 0.02 in ambulant; 4.81, 95% CI [−6.79,−2.82], p < 0.001 in non-ambulant). FVC% captured disease progression in non-ambulant DMD subjects, with an annual loss of 5.47% (95% CI [−6.48,−4.45], p < 0.001). Upper limb function measured with the Performance of Upper Limb (PUL 1.2) showed an annual loss of 4.13 points (95% CI [−4.79,3.47], p < 0.001) in the non-ambulant cohort. Measures of upper limb strength (MyoGrip and MyoPinch) showed a continuous decline independent of the ambulatory status, when reported as percentage predicted (grip force −5.51%, 95% CI [−6.54,−4.48], p < 0.001 in ambulant and a slower decline −2.86%; 95% CI −3.29,−2.43, p < 0.001, in non-ambulant; pinch force: −2.66%, 95% CI [−3.82,−1.51], p < 0.001 in ambulant and −2.23%, 95% CI [−2.92,−1.53], p < 0.001 in non-ambulant). Furthermore, we also explored the novel concept of a composite endpoint by combining respiratory, upper limb function and force domains: we were able to identify clear clinical progression in patients in whom an isolated measurement of only one of these domains failed to appreciate the yearly change. Our study contributes to the field of natural history of DMD, linking the ambulant and non-ambulant phases of the disease, and suggests that composite scores should be explored further.