Associative Increases in Amyotrophic Lateral Sclerosis Survival Duration With Non-invasive Ventilation Initiation and Usage Protocols

Abstract

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.

Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration

“…This is a secondary analysis of a retrospective cohort study comprising 8028 clinical visit records collected from 1585 patients at the Emory ALS Clinic (Emory University Hospital, Atlanta, GA, United States) into a FileMaker Pro relational database. Data collection, organization, and quality control methods are as previously published in prior work with this data set [5,20,44,45]. All data was de-identified and anonymized.…”

“…When comparing to prior work [49,50], it was not surprising that mood (measured via CIM) strongly correlated with physical health factors like respiratory metrics (i.e., FVC % predict, FVC, NIF, ALSFRS-R score, etc.) [5,45]. Moreover, existing studies that show respiratory interventions improve survival duration [51,52], although "mood" was not specifically assessed in prior work.…”

“…Some studies have pointed out that Bi-PAP usage compliance can be difficult in a segment of patients because it requires wearing a mask attached to a non-portable compressor plugged into an electrical outlet [5,45]. Depending on individualized respiratory function, patients must use Bi-PAP for prolonged periods of time, ranging from 8 hours/day (overnight while sleeping) up to 24 hours/day.…”

“…Depending on individualized respiratory function, patients must use Bi-PAP for prolonged periods of time, ranging from 8 hours/day (overnight while sleeping) up to 24 hours/day. Thus, while Bi-PAP usage is known to improve respiration and survival duration [5], it nonetheless can also reduce overall patient comfort, especially while sleeping; impede the patient's ability to communicate; and impede patient mobility. The novel result that Bi-PAP usage is associated with a more positive mood is important for prescribers and patients alike.…”

Dynamic Brain-Body Coupling of Breath-by-Breath O2-CO2Exchange Ratio with Resting State Cerebral Hemodynamic Fluctuations

“…Our brain-body coupling framework may apply in the investigation of brain responses to voluntary respiratory techniques like meditation, yoga breathing or tai-chi (Chaya et al, 2006;Garcia et al, 2018;Kesterson and Clinch, 1989;Ray et al, 2011;Sood et al, 2007;Tai et al, 2018;Wells et al, 2013;Zheng et al, 2015) to manipulate RGE for intervention purpose. This also includes the Bi-level Positive Airway Pressure (BiPAP) (Carlucci et al, 2015;Khamankar et al, 2018;Xiang et al, 2009) that applies to sleep apnea or Amyotrophic Lateral Sclerosis (ALS).…”