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

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 (FEV 1 ), 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, FEV 1 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 cmH 2 O (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.