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.
Respiratory failure is the most common cause of death in amyotrophic lateral sclerosis (ALS), which is a variably progressive neurologic disease without a known cure. Using a previously developed prediction model for respiratory failure, the current research will identify patients at high risk of respiratory failure upon diagnosis, will gather patient input on respiratory care early in disease, and will perform a small trial of a pulmonary exercise in patients at high risk of respiratory failure. This work will set the stage for larger trials of early respiratory therapies on high-risk patients, so that we may develop a personalized approach to treating respiratory failure in ALS.
