Non-invasive positive pressure ventilation (NPPV) can improve survival in ALS patients with advanced respiratory impairment, but it is not known if it is beneficial earlier in the disease course. A retrospective cohort study of patients with ALS was performed comparing survival from time of diagnosis in subjects who started NPPV use when their FVC was >or=65% predicted (Early NPPV) with subjects who started NPPV when their FVC was below 65% predicted (Standard NPPV). The Early group (n = 25) and the Standard group (n = 67) were similar except for pulmonary function (mean FVC in Early NPPV group = 74.3+/-10.1% predicted and 48.3+/-11.3 in Standard group, p<0.001). The median time from ALS diagnosis to death was significantly longer in the Early NPPV group (2.7 years vs. 1.8 years, p = 0.045). This remained significant after adjustment for potential confounding factors (H.R. = 0.55, 95% CI 0.31-0.98). Survival from time of diagnosis was nearly one year longer in the Early group. Until more definitive data are available from randomized trials, our findings suggest that clinicians either encourage earlier use of NPPV or use more sensitive tests for respiratory muscle impairment than upright FVC.

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The rapidity of progression of amyotrophic lateral sclerosis (ALS) to death or respiratory failure impacts patients, clinicians, and clinical investigators. This study compared the abilities of various pulmonary function tests to predict tracheostomy-free survival. We evaluated 95 ALS patients by determining upright and supine forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, arterial partial pressure of carbon dioxide (PaCO 2 ), and transdiaphragmatic sniff pressures (Pdi-sniff). Tracheostomy-free survival time was measured from the date of spirometry. Supine FVC, upright FVC, MIP, MEP, and Pdi-sniff were significantly associated with tracheostomy-free survival after controlling for nonpulmonary factors, whereas PaCO 2 was not. A normal supine FVC, MIP, or MEP was highly predictive for one-year survival. These tests are well suited to predict survival for trial enrollment and patient counseling. Supine FVC's simplicity of use and availability to ALS investigators makes it a particularly attractive predictor of one-year survival in ALS. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that ultimately leads to respiratory failure and death. A large degree of interpatient variability exists in the rate of progression, with some patients dying or requiring respiratory support within months and others having relatively prolonged survival. 10,17 The consequent uncertainty in survival is not only difficult for patients and their families, but also frustrates research on ALS, as it may be difficult to assemble a cohort of patients that can be expected to complete a clinical trial.Certain nonpulmonary factors, including female gender, advanced age, short time from symptom onset to diagnosis, and bulbar onset of disease are associated with shorter survival. 4,5,12,18 However, as ALS overwhelmingly brings death via respiratory compromise, pulmonary function tests should be particularly appropriate predictors of individual survival. 11,14 Upright forced vital capacity (FVC), the best studied of pulmonary tests, correlates with survival in ALS, 12,18 but may not be the best available pulmonary function test for the prediction of death or respiratory failure. Supine FVC and maximal inspiratory pressures (MIP) are more sensitive than upright FVC for the detection of respiratory muscle weakness. 8,9 Unlike upright FVC, maximal expiratory pressure (MEP) and other tests of expiratory function can predict a patient's ability to cough and clear airway secretions, 15 but these tests have not previously been shown to predict survival in ALS. The purpose of this study was to evaluate and compare the ability of the available pulmonary function tests to predict tracheostomy-free survival.We studied a cohort of ALS patients to evaluate the association between these pulmonary function tests and survival. The findings have relevance to the Abbreviations: ALS, amyotrophic lateral sclerosis; BiPAP, bilevel positive airway pressure; ⌬FVC, change (decline) from upri...