Early Respiratory Care in Amyotrophic Lateral Sclerosis Patients at High Risk for Respiratory Failure

Project Summary/Abstract
Respiratory failure commonly occurs in amyotrophic lateral sclerosis (ALS) and leads to significant morbidity
and mortality. The onset of respiratory weakness heralds an increased risk of aspiration related to bulbar
muscle weakness and ineffective cough, hypercapnic respiratory failure due to chronic hypoventilation, and
pulmonary infections, ultimately leading to death. Despite the key role of respiratory failure in the morbidity and
mortality associated with ALS, there remains uncertainty concerning optimum initiation and maintenance of
respiratory care for this disease. ALS has a very heterogeneous clinical presentation and symptom
progression, which causes variable evolution of respiratory involvement. Given the significance of respiratory
morbidity with this disease combined with the unclear timing, identifying high-risk subgroups may facilitate
studying outcomes of early respiratory interventions. Our group has published a clinical prediction tool which
can predict a high risk of respiratory failure within six months in ALS. We have also published a latent class
analysis to identify subphenotypes of ALS patients by their differing trajectories of forced vital capacity over
time. Applying our clinical prediction tool and knowledge of phenotypes to a sample of ALS patients would
identify a subgroup suitable for future clinical trials. However, given the emotional burden of ALS, patient
perspectives on respiratory interventions are critical to successful implementation. To our knowledge, a
prospective investigation on a cohort of ALS patients at high risk of respiratory failure has yet to be performed.
The goals of this study are to use our clinical prediction tool to identify the prevalence of newly-diagnosed ALS
patients at high risk of respiratory failure, to elucidate patient perspectives on early respiratory care, and to
implement a pilot trial of lung volume recruitment in high-risk patients. This proposal will involve a multicenter
study at three academic centers in Philadelphia. We will perform a prospective cohort study of patients with
ALS, apply our clinical prediction tool, and monitor them for respiratory failure over one year. We will use semi-
structured interviews to gather patient perspectives regarding circumstances under which they would accept
early respiratory care in ALS. Third, we will perform a single-arm pilot intervention of lung volume recruitment
in newly-diagnosed ALS patients at high risk of respiratory failure within six months.
This project will provide essential preliminary data for a Research Project Grant application that will (1) conduct
a randomized controlled trial of early respiratory therapy in high-risk ALS patients (2) elucidate physician and
caregiver perspectives regarding respiratory care in ALS, and (3) identify which characteristics are associated
with different trajectories of respiratory function, thus allowing for personalized medicine.

Grant Number: 5K23HL151879-05
NIH Institute/Center: NIH
Principal Investigator: Jason Ackrivo