The decline of respiratory function in amyotrophic lateral sclerosis patients and the role of non-invasive ventilation

Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by a poor prognosis, with an average survival of 3 to 5 years from symptom onset. Respiratory failure is the main cause of death, and non-invasive ventilation (NIV) is a cornerstone in the management of ALS patients. This single-center retrospective study was conducted at Siena University Hospital between 2010 and 2024 to analyze respiratory function parameters in ALS patients undergoing NIV, stratified by disease severity and followed over one year, to assess the relationship between lung function decline and the timing of NIV initiation. A total of 49 patients (29 males, 20 females; mean age 67±12 years) were enrolled, and 31 (63%) received NIV. Clinical and functional parameters, including forced vital capacity (FVC), pCO₂, respiratory symptoms at baseline, and longitudinal measurements of sitting FVC (FVCsit%), supine FVC (FVCsup%), and pCO₂, were collected and analyzed over time. Differences in FVC decline were observed according to the timing of NIV initiation. Among non-severe patients, those starting NIV at T0 showed a 22.5% reduction in FVC over a mean follow-up of 12.8±4.8 months. Patients initiating NIV at T2 exhibited a reported FVCsit decline of 26% (p=0.0488) and a survival of 51.3±50 months from NIV initiation, whereas those starting later (T3–T6) showed a greater decline (FVCsit decline 34%, p=0.0002) and shorter survival duration (15.7±28.6 months). These findings describe differences in respiratory function trajectories and observed survival among patients initiating NIV at different follow-up time points. However, the retrospective design, small sample size, baseline differences between groups, and potential confounding and survival-related selection bias limit causal interpretation. Further studies are needed to clarify the relationship between NIV initiation timing and clinical outcomes in ALS.