Respiratory phenotypes in ALS as determined by respiratory questions of the ALSFRS-R and their relation to respiratory tests.

Abstract

Respiratory insufficiency and its complications are the main cause of death in amyotrophic lateral sclerosis (ALS). Respiratory symptoms are scored in questions Q10 (dyspnoea) and Q11 (orthopnoea) of the revised ALS functional rating scale (ALSFRS-R). The association of respiratory test alterations with respiratory symptoms is unclear. Patients with ALS and progressive muscular atrophy were included. We recorded retrospectively demographic data, ALSFRS-R, forced vital capacity (FVC), maximal inspiratory (MIP) and expiratory (MEP) pressures, mouth occlusion pressure at 100ms (P0.1), nocturnal oximetry (SpO2 mean), arterial blood gases, phrenic nerve amplitude (PhrenAmpl). Three groups were categorized: G1- normal Q10 and Q11; G2- abnormal Q10; G3- abnormal Q10 and Q11 or only abnormal Q11. A binary logistic regression model explored independent predictors. We included 276 patients (153 men, onset-age 62.6±11.0yrs, disease duration 13.0±9.6mo, spinal-onset 182) with mean survival 40.1±26.0mo. Gender, onset-region and disease duration were similar in G1 (n=149), G2 (n=78) and G3 (n=49). Time to NIV was shorter in G3 (p<0.001), but survival was similar. ALSFRS-R subscores were significantly different (G1>G2>G3, p<0.001), except for lower limb subscore (p=0.077). G2 and G3 patients were older than G1 (p<0.001), had lower FVC, MIP, MEP, PhrenAmpl and SpO2 mean. Independent predictors for G2 were MIP and SpO2 mean; for G3 was only PhrenAmpl. These three distinct ALS phenotypic respiratory categories represent progressive stages of ventilatory dysfunction, supporting ALSFRS-R clinical relevance. Orthopnea is a severe symptom that should prompt NIV, being phrenic nerve response an independent predictor. Early NIV promotes similar survival for G2 and G3.