Comparative Performance of Different Respiratory Test Parameters for Detection of Early Respiratory Insufficiency in Patients With ALS

Objective: To compare the performance of different respiratory function testing in a multidisciplinary ALS clinic.

Methods: Demographics, clinical data, and respiratory testing parameters were abstracted from the medical records of patients who attended a multidisciplinary ALS clinic from 2008-2016. We compared the performance of the three primary respiratory test parameters used by Medicare for the initiation of non-invasive ventilation (NIV), (forced vital capacity (FVC) < 50% predicted, maximum inspiratory pressure (MIP) < 60 cm H20, and abnormal overnight pulse oximetry (OvOx)) on how they related to several clinically relevant attributes.

Results: 476 subjects were identified who underwent at least one respiratory test. Abnormalities of OvOx, MIP, and FVC occurred at a median of 1.6, 1.5, and 3.8 years from disease onset, respectively (p < 0.00001). Subjects with bulbar-onset ALS exhibited earlier abnormalities in MIP and FVC than in spinal-onset ALS (p <0.005). The median survival after an abnormal OvOx, MIP, or FVC test was 1.4, 1.4, and 0.9 years, respectively (p < 0.0001). Utilizing the ALS Functional Rating Score respiratory subscales, at the time of reported respiratory symptoms there were abnormalities in OvOx (60%), MIP (69%), and FVC (19%). Conversely, when respiratory parameter abnormalities preceded reported respiratory symptoms, this occurred with frequencies in OvOx (79%), MIP (42%) or FVC (24%). Four hundred forty-three subjects (93.1%) developed at least one abnormal respiratory measure meeting Medicare criteria for NIV consideration, but fewer than 50% in our cohort demonstrated NIV use. Improved survival in subjects using NIV was statistically significant in patients with bulbar-onset ALS.

Conclusions: Abnormalities in OvOx and MIP perform better than FVC at early detection of neuromuscular respiratory weakness in ALS. Initiation of NIV in patients with respiratory insufficiency may improve overall survival in ALS. In the setting of the COVID-19 pandemic, FVC and MIP have not been routinely performed due to infectious aerosol generation. OvOx, which we now routinely mail to patients’ homes, has been utilized exclusively during the COVID-19 pandemic, and allows for continued remote monitoring of respiratory status of patients with ALS.