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Phospholipid Levels in Blood during Community-Acquired Pneumonia
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 5, article id e0216379Article in journal (Refereed) Published
Abstract [en]

Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.

Place, publisher, year, edition, pages
Public Library of Science , 2019. Vol. 14, no 5, article id e0216379
Keywords [en]
Community-acquired pneumonia, phospholipids, infection, diagnosis, metabolomics
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:umu:diva-147058DOI: 10.1371/journal.pone.0216379ISI: 000467148400025PubMedID: 31063483OAI: oai:DiVA.org:umu-147058DiVA, id: diva2:1201274
Note

Originally included in thesis in manuscript form 

Available from: 2018-04-25 Created: 2018-04-25 Last updated: 2019-06-12Bibliographically approved
In thesis
1. Improved diagnosis and prediction of community-acquired pneumonia
Open this publication in new window or tab >>Improved diagnosis and prediction of community-acquired pneumonia
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Förbättrad diagnostik och prediktion vid samhällsförvärvad pneumoni
Abstract [en]

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Although there is wide variation in the microbial etiology, CAP may manifest with similar symptoms, making institution of proper treatment challenging. Therefore, etiological diagnosis is important to ensure that correct treatment and necessary infection control measures are instituted. This provides a challenge for conventional microbial diagnostic methods, typically based on culture and direct antigen tests. Moreover, existing molecular biomarkers have poor prognostic value. Few studies have investigated the global metabolic response during infection and virtually nothing is known about early responses after the start of antimicrobial treatment. The aim of this work was to improve diagnostic and predictive methods for CAP.

In paper I, a qPCR panel targeting 15 pathogens known to cause CAP was developed and evaluated. It combined identification of bacterial pathogens and viruses in the same diagnostic platform. The method proved to be robust and the results consistent with those obtained by standard methods. The panel approach, compared to conventional, selective diagnostics, detected a larger number of pathogens. In Paper II, whole blood samples from 65 patients with bacteremic sepsis were analyzed for metabolite profiles. Forty-nine patients with symptoms of sepsis, but later attributed to other diagnoses, were matched according to age and sex and served as a control group. Six metabolites were identified, all of which predicted growth of bacteria in blood culture. One of the metabolites, myristic acid, alone predicted bacteremic sepsis with a sensitivity of 100% and a specificity of 95%. Paper III and IV were based on a clinical study enrolling 35 patients with suspected CAP in need of hospital care. The aim was to study the metabolic response during the early phase of acute infection. The qPCR panel developed in Paper I was used to obtain the microbial etiological diagnosis. Paper IV focused on the global metabolic response and highlighted the dynamics of changes in major metabolic pathways during early recovery. A specific metabolite pattern for M. pneumoniae etiology was found. Four metabolites accurately predicted all but one patient as either M. pneumoniae etiology or not. Paper III looked at phospholipid levels during the first 48 hours after hospital admission. It was found that all major phospholipid species, especially the lysophosphatidyl-cholines, were pronouncedly decreased during acute infection. Levels started to increase the day after admission, reaching statistical significance at 48 hours. Paper II-IV showed that metabolomics might be used to study a number of different aspects of infection, such as etiology, disease progress and recovery. Knowledge of the metabolic profiles of patients may not only be utilized for biomarker discovery, as proposed in this work, but also for the future development of targeted therapies and supportive treatment.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2018. p. 80
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1960
Keywords
Community-acquired pneumonia, infection, diagnosis, qPCR, metabolites, metabolomics
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-147064 (URN)978-91-7601-873-6 (ISBN)
Public defence
2018-05-25, Bergasalen (Q0), Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2018-05-04 Created: 2018-04-25 Last updated: 2018-06-09Bibliographically approved

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Müller, Daniel C.Kauppi, AnnaEdin, AliciaGylfe, ÅsaSjöstedt, Anders B.Johansson, Anders

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