Correlations between measures of ALS respiratory function: is there an alternative to FVC?

Abstract

Background: An ongoing longitudinal study in six European sites includes a 3-monthly assessment of forced vital capacity (FVC), slow vital capacity (SVC), peak cough flow (PCF), and Sniff nasal inspiratory pressure (SNIP). The aim of this interim analysis was to assess the potential for SNIP to be a surrogate for aerosol generating procedures given COVID-19 related restrictions. Methods: This was a prospective observational study. Patients attending six study sites with King’s Stage 2 or 3 ALS completed baseline FVC/SVC/SNIP/PCF and repeated assessments 3 monthly. Data were collected from March 2018 to March 2020, after which a COVID-19 related study suspension was imposed. Correlations between the measures were calculated. A Bayesian multiple outcomes random-effects model was constructed to investigate rates of decline across measures. Results: In total, 270 cases and 828 assessments were included (Mean age 65.2 ± 15.4 years; 32.6% Female; 60% Kings stage 2; 81.1% spinal onset). FVC and SVC were the most closely correlated outcomes (0.95). SNIP showed the least correlation with other metrics 0.53 (FVC), 0.54 (SVC), 0.60 (PCF). All four measures significantly declined over time. SNIP in the bulbar onset group showed the fastest rate of decline. Discussion: SNIP was not well correlated with FVC and SVC, probably because it examines a different aspect of respiratory function. Respiratory measures declined over time, but differentially according to the site of onset. SNIP is not a surrogate for FVC and SVC, but is a complementary measure, declining linearly and differentiating spinal and bulbar onset patients.

Keywords:

• Amyotrophic lateral sclerosis
• respiratory assessment
• COVID-19
• clinical trials
• therapy
• ventilation

Ethics approval

Dublin: Ethics (Medical Research) Committee Beaumont Hospital, Dublin 9. Study Reference 15/62; Utrecht: Medisch Ethische Toetsings Commissie. Study Reference: MvdL/rgj/18/038367; Lleuven: Commissie Medische Ethiek Universitaire, Ziehenhuizen KU Lleuven. Study Reference: S60995; Turin: Comitato Etico Interaziendale, A.O.U. Citta’Della Salute e Della Scienza di Torino. Study Reference no. 0029137; Sheffield and London: IRAS 242722, Study reference STH20135.

Declaration of interest

Professor Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, and Cytokinetics. Prof Al-Chalabi reports consultancies for GSK, Cytokinetics, Biogen Idec, Treeway Inc, Chronos Therapeutics, OrionPharma, and Mitsubishi-Tanabe Pharma, and Chief Investigator roles for commercial clinical trials run by OrionPharma and Cytokinetics. PVD holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga België and the KU Leuven funds “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund”. Several authors of this publication are members of the European Reference Network for Rare Neuromuscular Diseases (ERN-NMD). This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the ’Rita Levi Montalcini’ Department of Neuroscience, University of Torino, Italy. This is in part an EU Joint Programme—Neurodegenerative Disease Research (JPND) project. CJM is supported by the NIHR Sheffield Biomedical Research Centre and the NIHR Clinical Research Facility at Sheffield Teaching Hospitals NHS Foundation Trust. JR is supported by the European Union Marie Skłodowska–Curie Action (n°846794). DMy is supported by the Health Research Board Ireland and the Irish Motor Neurone Disease Research Foundation under the HRB-MRCG scheme 2018.

Additional information

Funding

The study was funded by the Irish Motor Neurone Disease Research Foundation and sponsored by Cytokinetics. The project is supported through the following funding organizations under the aegis of JPND—www.jpnd.eu (United Kingdom, Medical Research Council [MR/L501529/1; MR/R024804/1] and Economic and Social Research Council [ES/L008238/1]) and through the Motor Neurone Disease Association. This study represents independent research part-funded by the National Institute for Health Research (NIHR), Biomedical Research Centre at South London, and Maudsley NHS Foundation Trust, and King’s College London.