Early Detection of Respiratory Impairments in ALS: A Novel Diagnostic Approach

Title: Early Detection of Respiratory Impairments in ALS: A Novel Diagnostic Approach Early detection of respiratory impairments in amyotrophic lateral sclerosis (ALS) is crucial for improving survival and quality of life. Current clinical tests, focusing on volitional forced breathing, fail to adequately challenge the respiratory neural drive, leading to undetected and therefore unmitigated loss of respiratory function in the early phases of the disease. Unlike limb muscles, respiratory muscles are controlled by both involuntary (ponto-medullary-spinal) and voluntary (cortico-spinal) pathways. This study proposes a novel diagnostic test to detect automatic breathing impairments in ALS, combining airway occlusion pressure (P0.1) and Chemosensitivity (Δ minute ventilation per Δ%SpO2). Preliminary data from asymptomatic genetic ALS carriers indicate deficits in automatic breathing, despite normal functional vital capacity (FVC) and maximum inspiratory pressure (MIP). We hypothesize that a composite score of P0.1 and Chemosensitivity can identify early respiratory impairments in ALS. The study aims to develop a linear prediction risk score and ROC cutoff to distinguish healthy controls from symptomatic ALS patients, and to identify subclinical impairments in asymptomatic/pre-symptomatic carriers. Microstructural changes in the brainstem-spinal cord and elevated blood neurofilament light chain (Nf-L) levels will be assessed to confirm the diagnostic test’s effectiveness. This innovative approach aims to fill a critical gap in ALS care by enabling earlier intervention and providing crucial markers for future clinical trials. Project Number: 1R21NS145175-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Jayakrishnan Nair | Institution: THOMAS JEFFERSON UNIVERSITY, PHILADELPHIA, PA | Award Amount: $196,250 | Activity Code: R21 | Study Section: Pulmonary Vascular Disease and Physiology Study Section [PVP] View on NIH RePORTER: https://reporter.nih.gov/project-details/11374663