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Author Notes:

Correspondence: Cassie S. Mitchell cassie.mitchell@bme.gatech.edu

Author contributions: NK data acquisition, statistical analysis, interpretation, critical review of the manuscript.

GC data acquisition, statistical analysis, critical review of the manuscript.

BW conception of study design, data acquisition.

CM conception of study design, data acquisition, interpretation of results, drafting of the manuscript.

Disclosure: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Research Funding:

Funding provided by the National Institute of Health Grants NS069616, NS098228, NS081426 to CM.


  • non-invasive ventilation
  • palliative care
  • neuromuscular disease
  • respiratory intervention
  • survival duration

Associative increases in amyotrophic lateral sclerosis survival duration with non-invasive ventilation initiation and usage protocols


Journal Title:

Frontiers in Neurology


Volume 9, Number JUL


Type of Work:

Article | Final Publisher PDF


Objective: It is hypothesized earlier non-invasive (NIV) ventilation benefits Amyotrophic Lateral Sclerosis (ALS) patients. NIV typically consists of the removable bi-level positive airway pressure (Bi-PAP) for adjunctive respiratory support and/or the cough assist intervention for secretion clearance. Historical international standards and current USA insurance standards often delay NIV until percent predicted forced vital capacity (FVC %predict) is < 50. We identify the optimal point for Bi-PAP initiation and the synergistic benefit of daily Bi-PAP and cough assist on associative increases in survival duration. Methods: Study population consisted of a retrospective ALS cohort (Emory University, Atlanta, GA, USA). Primary analysis included 474 patients (403 Bi-PAP users, 71 non-users). Survival duration (time elapsed from baseline onset until death) is compared on the basis of Bi-PAP initiation threshold (FVC %predict); daily Bi-PAP usage protocol (hours/day); daily cough assist usage (users or non-users); ALS onset type; ALSFRS-R score; and time elapsed from baseline onset until Bi-PAP initiation, using Kruskal-Wallis one-way analysis of variance and Kaplan Meier. Results: Bi-PAP users' median survival (21.03 months, IQR = 23.97, N = 403) is significantly longer (p < 0.001) than non-users (13.84 months, IQR = 11.97, N = 71). Survival consistently increases (p < 0.01) with FVC %predict Bi-PAP initiation threshold: < 50% (20.3 months); ≥50% (23.60 months); ≥80% (25.36 months). Bi-PAP usage > 8 hours/day (23.20 months) or any daily Bi-PAP usage with cough assist (25.73 months) significantly (p < 0.001) extends survival compared to Bi-PAP alone (15.0 months). Cough assist without Bi-PAP has insignificant impact (14.17 months) over no intervention (13.68 months). Except for bulbar onset Bi-PAP users, higher ALSFRS-R total scores at Bi-PAP initiation significantly correlate with higher initiation FVC %predict and longer survival duration. Time elapsed since ALS onset is not a good predictor of when NIV should be initiated. Conclusions: The "optimized" NIV protocol (Bi-PAP initiation while FVC %predict ≥80, Bi-PAP usage > 8 h/day, daily cough assist usage) has a 30. 8 month survival median, which is double that of a "standard" NIV protocol (initiation FVC %predict < 50, usage > 4 h/day, no cough assist). Earlier access to Bi-PAP and cough assist, prior to precipitous respiratory decline, is needed to maximize NIV synergy and associative survival benefit.

Copyright information:

© 2018 Khamankar, Coan, Weaver and Mitchell.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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