Lung function decline preceding chronic respiratory failure in spinal muscular atrophy: a national prospective cohort study

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

doi:10.1186/s13023-023-02634-4

Lung function decline preceding chronic respiratory failure in spinal muscular atrophy: a national prospective cohort study

Orphanet J Rare Dis. 2023 Feb 23;18(1):40. doi: 10.1186/s13023-023-02634-4.

Authors

Esther S Veldhoen¹, Camiel A Wijngaarde², Ruben P A van Eijk^{2

3}, Fay-Lynn Asselman², Negina Seddiqi⁴, Louise A M Otto², Marloes Stam², Inge Cuppen², Renske I Wadman², Roelie M Wösten van Asperen⁴, Erik H J Hulzebos⁵, Laura P Verweij van den Oudenrijn⁴, Bart Bartels⁵, Jasmijn Boezer⁴, M Gaytant⁶, Cornelis K van der Ent⁷, W Ludo van der Pol²

Affiliations

¹ Department of Pediatric Intensive Care, Wilhelmina Children's Hospital, University Medical Center Utrecht, 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 Biostatistics and Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Department of Pediatric Intensive Care, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, PO Box 85090, 3508 AB, Utrecht, The Netherlands.
⁵ Child Development and Exercise Center, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁶ Center of Home Mechanical Ventilation, Department of Pulmonology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁷ Department of Pediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Abstract

Background: Progressive lung function decline, resulting in respiratory failure, is an important complication of spinal muscular atrophy (SMA). The ability to predict the need for mechanical ventilation is important. We assessed longitudinal patterns of lung function prior to chronic respiratory failure in a national cohort of treatment-naïve children and adults with SMA, hypothesizing an accelerated decline prior to chronic respiratory failure.

Methods: We included treatment-naïve SMA patients participating in a prospective national cohort study if they required mechanical ventilation because of chronic respiratory failure and if lung function test results were available from the years prior to initiation of ventilation. We analyzed Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 s (FEV₁), Peak Expiratory Flow (PEF) and Maximum Expiratory Pressure (PE_max). We studied the longitudinal course using linear mixed-effects models. We compared patients who electively started mechanical ventilation compared to patients who could not be weaned after acute respiratory failure.

Results: We analyzed 385 lung function tests from 38 patients with SMA types 1c-3a. At initiation of ventilation median age was 18.8 years (IQR: 13.2-30.1) and median standardized FVC, FEV₁ and PEF were 28.8% (95% CI: 23.5; 34.2), 28.8% (95% CI: 24.0; 33.7) and 30.0% (95% CI: 23.4; 36.7), with an average annual decline of 1.75% (95% CI: 0.86; 2.66), 1.72% (95% CI: 1.04; 2.40) and 1.65% (95% CI: 0.71; 2.59), respectively. Our data did not support the hypothesis of an accelerated decline prior to initiation of mechanical ventilation. Median PE_max was 35.3 cmH₂O (95% CI: 29.4; 41.2) at initiation of mechanical ventilation and relatively stable in the years preceding ventilation. Median FVC, FEV_1, PEF and PE_max were lower in patients who electively started mechanical ventilation (p < 0.001).

Conclusions: Patterns of lung function decline cannot predict impending respiratory failure: SMA is characterized by a gradual decline of lung function. We found no evidence for an accelerated deterioration. In addition, PE_max remains low and stable in the years preceding initiation of ventilation. Patients who electively started mechanical ventilation had more restrictive lung function at initiation of ventilation, compared to patients who could not be weaned after surgery or a respiratory tract infection.

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

Publication types

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

MeSH terms

Adolescent
Adult
Child
Cohort Studies
Forced Expiratory Volume
Humans
Lung
Muscular Atrophy, Spinal*
Prospective Studies
Respiratory Insufficiency*
Vital Capacity