Natural history of lung function in spinal muscular atrophy

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

doi:10.1186/s13023-020-01367-y

Natural history of lung function in spinal muscular atrophy

Orphanet J Rare Dis. 2020 Apr 10;15(1):88. doi: 10.1186/s13023-020-01367-y.

Authors

Camiel A Wijngaarde¹, Esther S Veldhoen², Ruben P A van Eijk^{1

3}, Marloes Stam¹, Louise A M Otto¹, Fay-Lynn Asselman¹, Roelie M Wösten-van Asperen², Erik H J Hulzebos⁴, Laura P Verweij-van den Oudenrijn², Bart Bartels⁴, Inge Cuppen¹, Renske I Wadman¹, Leonard H van den Berg¹, Cornelis K van der Ent⁵, W Ludo van der Pol⁶

Affiliations

¹ Department of Neurology, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University, Heidelberglaan 100, 3508, GA, Utrecht, The Netherlands.
² Department of Paediatric Intensive Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
³ Biostatistics & Research Support, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Child Development and Exercise Centre, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
⁵ Department of Paediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
⁶ Department of Neurology, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University, Heidelberglaan 100, 3508, GA, Utrecht, The Netherlands. w.l.vanderpol@umcutrecht.nl.

Abstract

Background: Respiratory muscle weakness is an important feature of spinal muscular atrophy (SMA). Progressive lung function decline is the most important cause of mortality and morbidity in patients. The natural history of lung function in SMA has, however, not been studied in much detail.

Results: We analysed 2098 measurements of lung function from 170 treatment-naïve patients with SMA types 1c-4, aged 4-74 years. All patients are participating in an ongoing population-based prevalence cohort study. We measured Forced Expiratory Volume in 1 s (FEV₁), Forced Vital Capacity (FVC), and Vital Capacity (VC). Longitudinal patterns of lung function were analysed using linear mixed-effects and non-linear models. Additionally, we also assessed postural effects on results of FEV₁ and FVC tests. In early-onset SMA types (1c-3a), we observed a progressive decline of lung function at younger ages with relative stabilisation during adulthood. Estimated baseline values were significantly lower in more severely affected patients: %FEV₁ ranged from 42% in SMA type 1c to 100% in type 3b, %FVC 50 to 109%, and %VC 44 to 96%. Average annual decline rates also differed significantly between SMA types, ranging from - 0.1% to - 1.4% for FEV₁, - 0.2% to - 1.4% for FVC, and + 0.2% to - 1.7% for VC. In contrast to SMA types 1c-3a, we found normal values for all outcomes in later-onset SMA types 3b and 4 throughout life, although with some exceptions and based on limited available data. Finally, we found no important differences in FVC or FEV₁ values measured in either sitting or supine position.

Conclusions: Our data illustrate the longitudinal course of lung function in patients with SMA, which is characterised by a progressive decline in childhood and stabilisation in early adulthood. The data do not support an additional benefit of measuring FEV₁ or FVC in both sitting and supine position. These data may serve as a reference to assess longer-term outcomes in clinical trials.

Keywords: Lung function; Natural history; Spinal muscular atrophy.

Publication types

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

MeSH terms

Adult
Cohort Studies
Forced Expiratory Volume
Humans
Lung
Muscular Atrophy, Spinal*
Vital Capacity