Natural history of respiratory muscle strength in spinal muscular atrophy: a prospective national cohort study

Esther S Veldhoen; Camiel A Wijngaarde; Erik H J Hulzebos; Roelie M Wösten-van Asperen; Renske I Wadman; Ruben P A van Eijk; Fay Lynn Asselman; Marloes Stam; Louise A M Otto; Inge Cuppen; Feline E V Scheijmans; Laura P Verweij-van den Oudenrijn; Bart Bartels; Michael A Gaytant; Cornelis K van der Ent; W Ludo van der Pol

doi:10.1186/s13023-022-02227-7

Natural history of respiratory muscle strength in spinal muscular atrophy: a prospective national cohort study

Orphanet J Rare Dis. 2022 Feb 21;17(1):70. doi: 10.1186/s13023-022-02227-7.

Authors

Esther S Veldhoen^#¹, Camiel A Wijngaarde^#², Erik H J Hulzebos³, Roelie M Wösten-van Asperen⁴, Renske I Wadman², Ruben P A van Eijk^{2

5}, Fay Lynn Asselman², Marloes Stam², Louise A M Otto², Inge Cuppen², Feline E V Scheijmans², Laura P Verweij-van den Oudenrijn⁴, Bart Bartels³, Michael A Gaytant⁶, Cornelis K van der Ent⁷, W Ludo van der Pol²

Affiliations

¹ Department of Pediatric Intensive Care, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht University, PO box 85090, 3508 AB, Utrecht, The Netherlands. E.S.Veldhoen@umcutrecht.nl.
² Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
³ Child Development and Exercise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Department of Pediatric Intensive Care, University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht University, PO box 85090, 3508 AB, Utrecht, The Netherlands.
⁵ Biostatistics and Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁶ Department of Pulmonology, Center of Home Mechanical Ventilation, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁷ Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, Member of ERN-LUNG, University Medical Center Utrecht, Utrecht, The Netherlands.

^# Contributed equally.

Abstract

Background: Respiratory complications are the most important cause of morbidity and mortality in spinal muscular atrophy (SMA). Respiratory muscle weakness results in impaired cough, recurrent respiratory tract infections and eventually can cause respiratory failure. We assessed longitudinal patterns of respiratory muscle strength in a national cohort of treatment-naïve children and adults with SMA, hypothesizing a continued decline throughout life.

Methods: We measured maximal expiratory and inspiratory pressure (PE_max and PI_max), Sniff Nasal inspiratory pressure (SNIP), peak expiratory flow (PEF), and peak cough flow (PCF) in treatment-naïve patients with SMA. We used mixed-models to analyze natural history patterns.

Results: We included 2172 measurements of respiratory muscle function from 80 treatment-naïve patients with SMA types 1c-3b. All outcomes were lower in the more severe phenotypes. Significant differences in PEF were present between SMA types from early ages onwards. PEF decline was linear (1-2%/year). PEF reached values below 80% during early childhood in types 1c-2, and during adolescence in type 3a. PE_max and PI_max were severely lowered in most patients throughout life, with PE_max values abnormally low (i.e. < 80 cmH₂O) in virtually all patients. The PE_max/PI_max ratio was < 1 throughout life in all SMA types, indicating that expiratory muscles were most affected. All but SMA type 3b patients had a lowered PCF. Patients with types 2b and 3a had PCF levels between 160 and 270 L/min, those with type 2a around 160 L/min and patients with type 1c well below 160 L/min. Finally, SNIP was low in nearly all patients, most pronounced in more severely affected patients.

Conclusions: There are clear differences in respiratory muscle strength and its progressive decline between SMA types. We observed lower outcomes in more severe SMA types. Particularly PEF may be a suitable outcome measure for the follow-up of respiratory strength in patients with SMA. PEF declines in a rather linear pattern in all SMA types, with clear differences at baseline. These natural history data may serve as a reference for longer-term treatment efficacy assessments.

Keywords: Lung function; Natural history; Neuromuscular; Respiratory muscle strength; Spinal muscular atrophy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child, Preschool
Cohort Studies
Cough
Humans
Muscle Strength / physiology
Muscular Atrophy, Spinal*
Prospective Studies
Respiratory Insufficiency*
Respiratory Muscles