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Does celiac disease influence survival in sepsis?: A nationwide longitudinal study
Örebro University, School of Medical Sciences. Department of Pediatrics, Kalmar County Hospital, Kalmar, Sweden.
Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden; Zoonotic Ecology and Epidemiology, Faculty of Health and Life Sciences, Linnaeus University, Kalmar, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0003-1024-5602
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 4, article id e0154663Article in journal (Refereed) Published
Abstract [en]

Background: Individuals with celiac disease (CD) are at increased risk of sepsis. The aim of this study was to examine whether CD influences survival in sepsis of bacterial origin.

Methods: Nationwide longitudinal registry-based study. Through data on small intestinal biopsies from Sweden's 28 pathology departments, we identified 29,096 individuals with CD (villous atrophy, Marsh stage III). Each individual with CD was matched with five population-based controls. Among these, 5,470 had a record of sepsis according to the Swedish Patient Register (1,432 celiac individuals and 4,038 controls). Finally we retrieved data on mortality in sepsis patients through the Swedish Cause of Death Registry.

Results: CD was associated with a 19% increase in overall mortality after sepsis (95% confidence interval (CI) = 1.09-1.29), with the highest relative risk occurring in children (adjusted hazard ratio (aHR) = 1.62; 95%CI = 0.67-3.91). However, aHR for death from sepsis was lower (aHR = 1.10) and failed to reach statistical significance (95%CI = 0.72-1.69). CD did not influence survival within 28 days after sepsis (aHR = 0.98; 95%CI = 0.80-1.19).

Conclusions: Although individuals with CD seem to be at an increased risk of overall death after sepsis, that excess risk does not differ from the general excess mortality previously seen in celiac patients in Sweden. CD as such does not seem to influence short-term or sepsis-specific survival in individuals with sepsis and therefore is not an independent risk factor for poor prognosis in sepsis.

Place, publisher, year, edition, pages
San Francisco, USA: Public Library of Science , 2016. Vol. 11, no 4, article id e0154663
National Category
Immunology
Identifiers
URN: urn:nbn:se:oru:diva-50105DOI: 10.1371/journal.pone.0154663ISI: 000375211700121PubMedID: 27124735Scopus ID: 2-s2.0-84964859397OAI: oai:DiVA.org:oru-50105DiVA, id: diva2:925804
Funder
Swedish Research Council
Note

Funding Agency:

Kalmar County Council

Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2019-03-22Bibliographically approved
In thesis
1. Celiac disease and Infections
Open this publication in new window or tab >>Celiac disease and Infections
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Celiac disease (CD) is a chronic immune-mediated enteropathy affecting about 1% of the population worldwide. CD is triggered by ingestion of gluten in genetically predisposed individuals but additional factors (e.g. infections) are required for the disease to develop. CD also seems to be associated with infectious complications.

Aim: The main objective of this thesis was to increase the knowledge about the associations between CD and infections.

Methods: Epidemiological and laboratory approaches. Studies I-III used a data set consisting of small intestinal biopsy reports. The biopsies were taken in 1969-2008 and collected in 2006-2008. A total of 29,096 individuals with CD, 13,306 with inflammation and 3,719 with potential CD were identified. Each individual was matched with up to 5 controls from the general population (n= 228,632). Through linkage of the data to the Patient Register study I examined the risk of hospital visits due to respiratory syncytial virus (RSV) in children <2 years prior to onset of CD. Study II used the Patient Register and Cause of Death Register to assess whether CD affects the outcome in sepsis. Study III linked the data to microbiological data bases and the Public Health Agency to estimate risk of invasive pneumococcal disease (IPD) in CD. In study IV children with CD and controls were recruited from Kalmar County Hospital. Complement activation (C3a and sC5b-9) in plasma were analysed after incubation with pneumococci.

Results: Study I found that children with CD were more likely than controls to have attended hospital due to RSV infection prior to diagnosis (odds ratio 1.46; 95% confidence interval (CI)=1.02-2.07). CD did not seem to influence survival in sepsis (adjusted hazard ratio (HR) 1.10 95%CI=0.72-1.69) (study II). Study III indicated a 46% risk increase for individuals with CD to acquire IPD (HR 1.46; 95%CI=1.05-2.03) but study IV did not reveal any differences in complement response in regard to CD status (p=0.497and p=0.724), explaining this excess risk.

Conclusion: This thesis supports associations between CD and infections preceding and complicating diagnosis. However, CD does not seem to influence the outcome in a severe infection like sepsis and altered complement function is unlikely to be responsible for the excess IPD risk in CD.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2019. p. 97
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 188
Keywords
Celiac disease, small intestinal, infection, respiratory syncytial virus, sepsis, streptococcus pneumoniae, complement, cohort, register
National Category
General Practice
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-71643 (URN)978-91-7529-278-6 (ISBN)
Public defence
2019-03-22, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-04-10Bibliographically approved

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Röckert Tjernberg, AnnaLudvigsson, Jonas F.

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