# name
Decreased plasma phospholipid concentrations and increased acid
                sphingomyelinase activity are accurate biomarkers for
                community-acquired pneumonia

# metadata.dc.description.abstract[].value
Background: There continues to be a great need for better biomarkers and host-directed treatment targets for
community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small
molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and
sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce
end-organ damage.
Methods: We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid
sphingomyelinase activity, in plasma from patients with CAP (n=29, sampled on admission and 4 subsequent time
points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n=13) as a clinically important
disease control, and 33 age- and sex-matched controls.
Results: Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement.
Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and cer‑
amides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced,
but also difered qualitatively, e.g. by increases in selected sphingomyelins. We identifed highly accurate biomark‑
ers for CAP (AUC≤0.97) and COPD (AUC≤0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD
(AUC≤0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins
were also markedly decreased in S. aureus-infected human A549 and diferentiated THP1 cells. Correlations with
C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting
that these markers refect more than merely infammation. Consistent with the increased ceramide concentrations,
increased acid sphingomyelinase activity accurately distinguished CAP (fold change=2.8, AUC=0.94) and COPD
(1.75, 0.88) from Controls and normalized with clinical resolution Conclusions: The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to
reveal diferences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that
the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore,
they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve
clinical outcome of CAP.

# metadata.dc.relation.ispartof[].value
Journal of Translational Medicine, 2019, vol. 17

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Decreased plasma phospholipid concentrations and increased acid
                sphingomyelinase activity are accurate biomarkers for
                community-acquired pneumonia