Abstract

Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach normal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during convalescence to 1.7-fold above levels measured in healthy control. Our data suggest that dysregulated amino acid metabolism in CAP partially persists through clinical recovery and that amino acid metabolism constitutes a source of promising biomarkers for CAP. In particular, total amino acids, asparagine, and threonine may constitute plasma biomarker candidates for the differentiation between CAP and infection-triggered COPD exacerbation and, perhaps, the detection of pneumonia in COPD.

1. Introduction

Community-acquired pneumonia (CAP) continues to exert a major burden on populations and health care delivery systems worldwide [1,2]. Despite the wide clinical use of acute phase reactants such as C-reactive protein (CRP) and procalcitonin (PCT) as part of the diagnostic work-up, there is still a great need for more accurate blood biomarkers for CAP, not only to differentiate it from other infectious and non-infectious disorders with similar clinical presentations but also to aid in post-diagnosis treatment decisions such as cessation of antibiotic treatment [3]. The differentiation from chronic obstructive pulmonary disease (COPD) exacerbation presents a clinical challenge in a subpopulation of patients, as COPD flares are often triggered by respiratory infections and may feature symptoms similar or identical to lower respiratory infections. In addition, it is important to identify COPD patients who present with co-existing pneumonia and may require different antibiotic regimes and evaluations, e.g., a heightened awareness of the risk of pneumogenic sepsis. Indeed, COPD is among the most common comorbidities that confer a heightened risk of severe CAP [4].

Read more...