title: Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: a comprehensive review of the literature.
abstract: Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure. Our analysis supports the utility of MIP for the early evaluation of respiratory muscle strength, especially of the diaphragm, in patients with NMD and as a surrogate endpoint in clinical trials of therapies for NMD.
authors.affiliation: Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilian University, Ziemssenstr. 1a, D-80336, Munich, Germany. bschoser@med.uni-muenchen.de.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
authors.affiliation: Division of Pediatric Pulmonology, Asthma, and Sleep Medicine, Stanford University, Stanford, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Fong
authors.affiliation: University Hospitals Birmingham, Selly Oak Hospital, Birmingham, UK.
authors.forename: Tarekegn
authors.initials: T
authors.lastname: Geberhiwot
authors.affiliation: Department of Haematology, Royal Free & University College Medical School, London, UK.
authors.forename: Derralynn
authors.initials: D
authors.lastname: Hughes
authors.affiliation: Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Kissel
authors.affiliation: Department of Respiratory Medicine, University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, England, UK.
authors.forename: Shyam C
authors.initials: SC
authors.lastname: Madathil
authors.affiliation: Intensive Care Unit and Home Ventilation Unit, Raymond Poincare Teaching Hospital, Garches, France.
authors.forename: David
authors.initials: D
authors.lastname: Orlikowski
authors.affiliation: NIHR Respiratory Biomedical Research Unit of the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, UK.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Polkey
authors.affiliation: Greater Manchester Neurosciences Unit, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Roberts
authors.affiliation: Department of Pediatric Pulmonology and Allergology, Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Harm A W M
authors.initials: HA
authors.lastname: Tiddens
authors.affiliation: Department of Sleep Medicine and Neuromuscular Disorders, University of Münster, Münster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Young
mesh_terms: D006801:Humans; D000072277:Maximal Respiratory Pressures; D009468:Neuromuscular Diseases / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012131:Respiratory Insufficiency / Q000503:physiopathology; D013147:Spirometry
keywords: Endpoint; Maximum inspiratory pressure; Neuromuscular disease; Pulmonary function testing; Respiratory failure; Spirometry; Survival