Baseline Predictors of Noninvasive Ventilation Use in Amyotrophic Lateral Sclerosis

Abstract

SESSION TITLE: Pulmonary Manifestations of Systemic Diseases SESSION TYPE: Original Investigation Slide PRESENTED ON: Wednesday, November 1, 2017 at 07:30 AM - 08:30 AM PURPOSE: Respiratory failure due to neuromuscular weakness is the most common cause of death for patients with Amyotrophic Lateral Sclerosis (ALS). Non-invasive ventilation (NIV) can improve quality of life and potentially improve survival. However, due to variable progression of ALS, the timing of onset of respiratory weakness remains uncertain. The ability to predict non-invasive ventilation use may help guide patient-physician communication, specialist referral, monitoring decisions, and clinical trial design. In this study, we sought to determine the baseline risk factors for eventual initiation of NIV. METHODS: We performed a retrospective cohort study of 572 patients who met El Escorial criteria for Suspected, Possible, Probable, or Definite ALS. All patients were seen in a multidisciplinary Neurology outpatient clinic at the University of Pennsylvania. Outpatient visits occurred approximately every three months between May 2010 and October 2016. Study variables included demographics, ALS Functional Rating Scale-Revised (ALSFRS-R) score, height, weight, comorbid conditions, smoking history, symptom onset date, symptom onset site, El Escorial criteria, forced vital capacity (FVC) in seated position, NIV initiation date, and date of death. We used univariate and multivariate Cox proportional hazard models, censoring at date of death or last visit date. The final multivariate model used backward elimination. RESULTS: The median age of diagnosis was 65.2 (interquartile range, 57.3 to 72.7) years and 58.4% were male. There were 812 person-years of follow-up time, and 45.5% (n=260) were initiated on NIV during the study period. The median time to NIV initiation was 184 days (interquartile range, 37 to 386 days). In a multivariate analysis, factors significantly associated with risk of NIV included older age at diagnosis (per 10 years, HR 1.27, 95% CI 1.13 - 1.44, p<0.001), fewer years between symptoms and diagnosis (HR 0.73, 95% CI 0.64-0.83, p<0.001), being underweight (HR 2.18, 95% CI 1.24-3.82, p=0.007), African-American race (HR 1.83, 95% CI 1.19-2.81, p=0.006), lower decile of percent predicted FVC (HR 1.15, 95% CI 1.09-1.22, p<0.001), history of hypertension (HR 1.34, 95% CI 1.01-1.78, p=0.040), lumbosacral symptom onset (reference: bulbar onset, HR 1.67, 95% CI 1.17-2.38, p=0.005), and El Escorial criteria of Suspected ALS (HR 0.62, 95% CI 0.41-0.95, p=0.027) or Possible ALS (HR 0.67, 95% CI 0.44-1.00, p=0.050) with a reference of Definite ALS. CONCLUSIONS: We identified baseline risk factors that were significantly associated with initiation of NIV in ALS patients. To our knowledge, this is the largest cohort study of ALS patients to identify risk factors for respiratory insufficiency. These factors may reveal important mechanisms of respiratory failure in ALS, which could be targeted with novel therapies. CLINICAL IMPLICATIONS: While many of the risk factors were not modifiable (e.g., older diagnosis age), such predictors could be used to develop a risk prediction score, inform communication with patients, guide clinical trial design, as well as facilitate early referral to pulmonologists. DISCLOSURE: The following authors have nothing to disclose: Jason Ackrivo, E. Wileyto, Lauren Elman, John Hansen-Flaschen, Steven Kawut No Product/Research Disclosure Information