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

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 second (FEV1), Peak Expiratory Flow (PEF) and Maximum Expiratory Pressure (PEmax). We studied the longitudinal course using linear mixed-effects models. Results We analyzed 1171 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. We did not observe an accelerated decline in the year before initiation of mechanical ventilation. Median PEmax was 35.3 cmH2O (95%CI: 29.4; 41.2) at initiation of mechanical ventilation and relatively stable in the years preceding ventilation. Conclusions Patterns of lung function decline cannot predict impending respiratory failure: SMA is characterized by a gradual decline of lung function, without an accelerated deterioration prior to respiratory failure. In addition, PEmax remains low and stable in the years preceding chronic respiratory failure.