Single breath counting is an effective screening tool for forced vital capacity in ALS

Abstract

Objective: To measure the correlation between single breath counting (SBC) and forced vital capacity (liters, FVC_L) in amyotrophic lateral sclerosis (ALS) patients and to define the utility of SBC for determining when patients meet the threshold for initiation of noninvasive positive pressure ventilation (FVC < 50% predicted [FVC_pred]). Methods: Both patient paced (SBCpp) or externally paced (SBCep) counting along with FVC_L+pred and standard clinical data were collected. Linear regression was used to examine SBCpp and SBCep as a predictor of FVC_L. Receiver operating characteristic curve analysis evaluated the sensitivity and specificity of SBC categorically predicting FVC_pred of ≤50%. Results: In 30 ALS patients, SBC explained a moderate proportion of the variance in FVC_L (SBCpp: R²= 0.431, p < 0.001; SBCep: R² = 0.511, p < 0.01); this proportion improved when including covariates (SBCpp: R²= 0.635, p < 0.01; SBCep: R²= 0.657, p < 0.01). Patients with minimal speech involvement performed similarly in unadjusted (SBCpp: R² = 0.511, p < 0.01; SBCep: R²= 0.595, p < 0.01) and adjusted (SBCpp: R² = 0.634, p < 0.01; SBCep: R²= 0.650, p < 0.01) models. SBCpp had 100% sensitivity and 60% specificity (area under curve (AUC) = 0.696) for predicting FVC_pred <50%. SBCep had 100% sensitivity and 56% specificity (AUC = 0.696). With minimal speech involvement SBCpp and SBCep both had 100% sensitivity and 76.1% specificity (SPCpp: AUC = 0.845; SBCep: AUC = 0.857). Conclusions: SBC explains a moderate proportion of variance in FVC and is an extremely sensitive marker of poor FVC. When FVC cannot be obtained, such as during the current COVID-19 pandemic, SBC is helpful in directing patient care.

Keywords:

• Single breath count
• amyotrophic lateral sclerosis
• neuromuscular disease
• ventilation
• biomarker

Declaration of interest

Colin Quinn: advisory board and consulting fees from Amylyx Pharmaceuticals, Acceleron Pharma, and Amicus Therapeutics. Research support from Amylyx Pharmaceuticals, Acceleron Pharma, Amicus Therapeutics, and Orphazyme.

Corey McMillan: receives research funding from Biogen Inc., and provides consulting services for Invicro and Axon Advisors on behalf of Translational Bioinformatics, LLC. He also receives an honorarium as Associate Editor of NeuroImage: Clinical.

Margaret A. Owegi: nothing to disclose.

Kelly Almasy: nothing to disclose.

Catherine Douthwright: nothing to disclose.

Diane McKenna-Yasek: nothing to disclose.

Namita Goyal: received research support from Brainstorm Cell Therapeutics, Cytokinetics, Fulcrum, Kezar, Novartis, Octapharma, Orion, and Orphazyme.

Dr. Goyal has served on Advisory Boards for Acceleron, Alexion, Argenx, Biogen, CSL Behring, Cytokinetics, MT Pharma, Novartis, Sanofi Genzyme, and Sarepta. In relation to these activities, she has received travel reimbursement and honoraria. She has also served on the speaker’s bureau for CSL.

James Berry: advisory board consulting fees from Biogen, Clene Nanomedicine, and Alexion. He has received research support from Biogen, MT Pharma of America, Anelixis Therapeutics, Amylyx Therapeutics, Brainstorm Cell Therapeutics, Genentech, nQ Medical, NINDS, Muscular Dystrophy Association, ALS One, and ALS Finding A Cure.

Robert H. Brown Jr: scientific co-founder and consultant ApicBio, Inc. Holds equity in Amylyx and Imstar.

Author contributions

Dr. Colin Quinn: Conceptualization, design, and drafting the manuscript.

Dr. Corey McMillan: Statistical analysis and drafting the manuscript.

Dr. Margaret A. Owegi and Kelly Almasy: Collection of clinical data.

Catherine Douthwright and Diane McKenna-Yasek: Collection of clinical data and drafting the manuscript.

Namita A. Goyal, James Berry, and Robert H. Brown Jr: Conceptualization, design, and drafting the manuscript.

Data availability statement

Anonymized data is available upon request from any qualified investigator for the purposes of replicating procedures and results.