Effects of Continuous Albuterol Inhalation on Serum Metabolome in Healthy Subjects: More Than Just Lactic Acid

Craig D. Nowadly, Shu Yi Liao, John S. Rose

Research output: Contribution to journalArticlepeer-review

Abstract

Treatment with β2-agonists may cause elevated lactic acid, the end product of anaerobic metabolism of glucose. It has been proposed that lactic acidosis associated with β2-agonists is caused by changes to direct biochemical impacts on glycolysis, gluconeogenesis, pyruvate metabolism, and free fatty acid production. However, much remains unknown, and there is a paucity of evidence regarding the underlying chemical changes associated with this lactic acidosis. The goal of our study was to investigate the impact of 1 hour of continuous albuterol on the untargeted serum metabolome of healthy subjects. Twenty-four healthy participants received 7.5 mg of continuous albuterol for 1 hour. Baseline, 1-hour, and 2-hour lactic acid levels were drawn. Samples obtained at baseline and 1 hour were sent for untargeted metabolomic profiling. Participants had a baseline lactic acid of 1.45 ± 0.46 mmol/L. On average, lactate levels increased 0.33 ± 0.67 mmol/L after 1 hour (P =.02) and remained elevated at 2 hours (0.32 ± 0.72 mmol/L, P =.02), although there was overlap in lactate levels across times. For metabolomic analysis, fatty acids, organic acids, and sugars were elevated, and amino acids were reduced. Lactic acid and pyruvic acid metabolites, however, did not significantly change (after false discovery rate adjustment). In healthy participants, continuous albuterol alters the serum metabolome, but this change may not be clinically significant. The data support recent hypotheses that β2-receptor activation stimulates lactic acid production, altering aerobic glycolysis, gluconeogenesis, and free fatty acid production.

Original languageEnglish (US)
Pages (from-to)649-655
Number of pages7
JournalJournal of Clinical Pharmacology
Volume61
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • asthma
  • beta receptor
  • beta-agonist
  • hyperlactatemia
  • lactate
  • lactic acidosis
  • serum metabolomics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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