TY - JOUR
T1 - Natural history of respiratory muscle strength in spinal muscular atrophy
T2 - a prospective national cohort study
AU - Veldhoen, Esther S.
AU - Wijngaarde, Camiel A.
AU - Hulzebos, Erik H.J.
AU - Wösten-van Asperen, Roelie M.
AU - Wadman, Renske I.
AU - van Eijk, Ruben P.A.
AU - Asselman, Fay Lynn
AU - Stam, Marloes
AU - Otto, Louise A.M.
AU - Cuppen, Inge
AU - Scheijmans, Feline E.V.
AU - den Oudenrijn, Laura P.Verweij van
AU - Bartels, Bart
AU - Gaytant, Michael A.
AU - van der Ent, Cornelis K.
AU - van der Pol, W. Ludo
N1 - Funding Information:
We thank all patients with SMA who have been participating in our ongoing study and the Dutch organization for Neuromuscular Diseases (Spierziekten Nederland) for their continuing support of our research.
Funding Information:
Our work was financially supported by the Prinses Beatrix Spierfonds (WAR 08-24, 13-07, and 14-26) and stichting Spieren voor Spieren.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/2/21
Y1 - 2022/2/21
N2 - 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 cmH
2O) 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.
AB - 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 cmH
2O) 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.
KW - Child, Preschool
KW - Cohort Studies
KW - Cough
KW - Humans
KW - Muscle Strength/physiology
KW - Muscular Atrophy, Spinal
KW - Prospective Studies
KW - Respiratory Insufficiency
KW - Respiratory Muscles
KW - Spinal muscular atrophy
KW - Neuromuscular
KW - Lung function
KW - Respiratory muscle strength
KW - Natural history
UR - http://www.scopus.com/inward/record.url?scp=85125154727&partnerID=8YFLogxK
U2 - 10.1186/s13023-022-02227-7
DO - 10.1186/s13023-022-02227-7
M3 - Article
C2 - 35189949
AN - SCOPUS:85125154727
SN - 1750-1172
VL - 17
SP - 1
EP - 11
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
IS - 1
M1 - 70
ER -