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. 2023 May 24:15:1188827.
doi: 10.3389/fnagi.2023.1188827. eCollection 2023.

Serum chloride as a respiratory failure marker in amyotrophic lateral sclerosis

Umberto Manera  1   2 , Maurizio Grassano  1 , Enrico Matteoni  1 , Alessandro Bombaci  1 , Rosario Vasta  1 , Francesca Palumbo  1 , Maria Claudia Torrieri  3 , Paolo Cugnasco  1 , Cristina Moglia  1   2 , Antonio Canosa  1   2   4 , Adriano Chiò  1   2   4 , Andrea Calvo  1   2
Affiliations

Serum chloride as a respiratory failure marker in amyotrophic lateral sclerosis

Umberto Manera et al. Front Aging Neurosci. .

Abstract

Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS) and occurs with great variability among patients according to different phenotypic features. Early predictors of respiratory failure in ALS are important to start non-invasive ventilation (NIV). Venous serum chloride values correlate with carbonate (HCO3-) blood levels and reflect metabolic compensation of respiratory acidosis. Despite its wide availability and low cost, few data on serum chloride as a prognostic marker exist in ALS literature. In the present study, we evaluated serum chloride values at diagnosis as prognostic biomarkers for overall survival and NIV adaptation in a retrospective center-based cohort of ALS patients. We collected all ALS patients with serum chloride assessment at diagnosis, identified through the Piemonte and Valle d'Aosta Register for ALS, evaluating the correlations among serum chloride, clinical features, and other serum biomarkers. Thereafter, time-to-event analysis was modeled to predict overall survival and NIV start. We found a significant correlation between serum chloride and inflammatory status markers, serum sodium, forced vital capacity (FVC), ALS functional rating scale-revised (ALSFRS-R) item 10 and 11, age at diagnosis, and weight loss. Time-to-event analysis confirmed both in univariate analysis and after multiple confounders' adjustment that serum chloride value at diagnosis significantly influenced survival and time to NIV start. According to our analysis, based on a large ALS cohort, we found that serum chloride analyzed at diagnosis is a low-cost marker of impending respiratory decompensation. In our opinion, it should be added among the serum prognostic biomarkers that are able to stratify patients into different prognostic categories even when performed in the early phases of the disease.

Keywords: amyotrophic lateral sclerosis; non-invasive ventilation; respiratory failure; serum chloride; survival.

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Conflict of interest statement

ACal received research grant from Cytokinetics. ACh served on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Denali Pharma, AC Immune, Biogen, Lilly, and Cytokinetics. The sponsor organizations had no role in data collection and analysis and did not participate to writing and approving the manuscript. The information reported in the manuscript has never been reported elsewhere. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Kaplan–Meier analysis on overall survival, performed comparing patients divided by serum chloride median value (103.0 mmol/L). Log-rank test p = 0.003. (B) Kaplan–Meier analysis on time to non-invasive ventilation (NIV) start, performed comparing patients divided by serum chloride median value (103.0 mmol/L). Log-rank test p = 0.010.
See this image and copyright information in PMC

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