Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary

Abstract

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

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

“…Inclusion and exclusion criteria may be age and disease‐stage based. The assessment and evaluation of clinically significant and reproducible outcomes are also challenging and need to be the topic of current research so that future studies can lead to clinically applicable conclusions about the implementation of emerging therapies . As available treatments have both benefits and drawbacks and therefore handling these patients is proven to be a complex matter of fine‐tuning for clinicians, demanding much forethought.…”

American Thoracic Society 2018 pediatric core curriculum

“…British Thoracic Society guideline recommends that forced vital capcity (FVC) should be measured in all NMD patients who are capable of performing spirometry and should be considered as the primary longitudinal outcome measure. FVC has the strongest association with mortality,with poor survival associated with FVC less than 1 L 57. Forced expiratory volume first second (FEV1), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), peak cough flow (PCF), peak expiratory flow (PEF), and sniff nasal inspiratory pressure (SNIP) should be considered as secondary endpoints 57.…”

“…FVC has the strongest association with mortality,with poor survival associated with FVC less than 1 L 57. Forced expiratory volume first second (FEV1), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), peak cough flow (PCF), peak expiratory flow (PEF), and sniff nasal inspiratory pressure (SNIP) should be considered as secondary endpoints 57. The Cooperative International Neuromuscular Research Group (CINRG) Duchenne natural history study (DNHS) showed that both FVC and PEF closely correlate respiratory complications and rate of hospitalizations in patients with Duchenne Muscular Dystrophy (DMD) [57][58][59].…”

“…Arm span has been suggested as an alternative measure for height; however, contractures across the elbow, wrist, or fingers make arm span an inaccurate surrogate for height. Ulna length is now commonly used since it is a single bone measure 57. It is important to note that slight measurement errors can produce a multiplied effect on height estimate.Clinical assessment of respiratory health should be directed toward identifying progressive muscle weakness, ability to cope with respiratory infection, proper nutrition and growth, signs of aspiration, and progression of scoliosis, and sleep-disordered breathing 51,57.…”

“…Ulna length is now commonly used since it is a single bone measure 57. It is important to note that slight measurement errors can produce a multiplied effect on height estimate.Clinical assessment of respiratory health should be directed toward identifying progressive muscle weakness, ability to cope with respiratory infection, proper nutrition and growth, signs of aspiration, and progression of scoliosis, and sleep-disordered breathing 51,57. Recent studies have reported loss of ambulation, loss of upper, and lower extremity functions correlate with the decline of FVC, which further highlights the importance of individual functional assessment at each visit 59,60.…”