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Effect of oral diclofenac intake on faecal calprotectin
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Primary Health Care in Central County. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. National Board Forens Med, Linkoping, Sweden.
Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
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2016 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 1, p. 28-32Article in journal (Refereed) Published
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Text
Abstract [en]

Background. NSAIDs are a known source of increased faecal calprotectin (FC) levels. Currently, there is a lack of knowledge about how long it takes for an increased FC level to return to normal after NSAID intake. Objective. The aim was to investigate how oral diclofenac intake affects FC levels and assess how long it takes for an increased FC level to return to normal after oral diclofenac intake. Material and methods. Thirty healthy volunteers received diclofenac 50 mg three times daily for 14 days. Participants provided a stool sample on Days 0, 2, 4, 7, 14 during intake and Days 17, 21, 28 after discontinuation. FC levels were then followed at 7-day intervals until normalization. Results. During diclofenac intake, eight participants (27%) had FC levels exceeding the upper limit of normal (median, 76 mu g/g; range, 60-958 mu g/g), corresponding to 8.3% of measurements. FC was not constantly increased and became normal in most participants during diclofenac intake. FC levels were on average significantly higher during intake (M = 9.5, interquartile range (IQR) = 13.4) than on baseline (M = 7.5, IQR = 0.0), p = 0.003. After discontinuation, two participants had increased FC on Days 17 and 21, respectively. No significant differences in FC levels were found between baseline and measurements after discontinuation. Two weeks after discontinuation, all participants had normal FC levels. Conclusions. Short-term oral diclofenac intake is associated with increased FC levels. However, the likelihood of an increased test result is low. Our results suggest that 2 weeks of diclofenac withdrawal is sufficient to get an uninfluenced FC test result.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2016. Vol. 51, no 1, p. 28-32
Keywords [en]
intestinal inflammation; proton pump inhibitors; NSAIDs; non-steroidal anti-inflammatory agents; diclofenac; calprotectin
National Category
Physiology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:liu:diva-127586DOI: 10.3109/00365521.2015.1066421ISI: 000373621900005PubMedID: 26200803OAI: oai:DiVA.org:liu-127586DiVA, id: diva2:925976
Note

Funding Agencies|County Council of Ostergotland, Sweden

Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2023-08-18
In thesis
1. Faecal Calprotectin Diagnostics: Focus on Primary Care and Suspected Sources of Error
Open this publication in new window or tab >>Faecal Calprotectin Diagnostics: Focus on Primary Care and Suspected Sources of Error
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with gastrointestinal symptoms often present a diagnostic challenge for general practitioners. Faecal calprotectin (FC) is commonly used as a marker of intestinal inflammation and is useful for differentiating between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), as well as for the follow-up of patients with IBD and monitoring treatment response. However, several other causes of increased FC levels have been acknowledged, including intake of non-steroidal anti-inflammatory drugs or proton pump inhibitors and respiratory infections. Currently, there is insufficient knowledge about how these factors affect FC levels. It is crucial that physicians who use calprotectin as a diagnostic tool have the ability to conduct a sound evaluation of the test result to ensure accurate clinical decisions, and potentially avoid unnecessary referrals and invasive investigations.

The aim of this thesis was to investigate the contribution of FC in the diagnostics of gastrointestinal disease in primary care, its diagnostic value and accuracy as a predictor of gastrointestinal disease and the influence of different sources of error on calprotectin levels. In particular, the effects of oral diclofenac (a non-steroidal anti-inflammatory drug [NSAID]), omeprazole (a proton pump inhibitor [PPI]) and respiratory tract infection on FC levels are investigated. The normalization interval after cessation of diclofenac and omeprazole is assessed.

The first study is a retrospective analysis of data on all FC tests on adults conducted in primary care in Östergötland County in 2010. A higher proportion of patients with a positive FC result were diagnosed with IBD and organic gastrointestinal disease compared with those with a negative FC result. Predictors of IBD were positive FC, diarrhoea, rectal bleeding and male sex. Predictors of organic gastrointestinal disease were found to be positive FC, age >35 years, abnormal clinical findings and duration <3 months. FC had the highest sensitivity and negative predictive value compared with demographic factors, symptoms and duration. Intake of NSAIDs, PPIs and acetyl salicylic acid showed marginal effects on the diagnostic accuracy of FC for IBD and organic gastrointestinal disease. Among patients with a negative FC test, on whom no further investigations were performed, no missed diagnoses of IBD or organic gastrointestinal disease were detected at a 5-year follow-up.

The second study investigates the effect of diclofenac intake on FC levels. We found that shortterm intake of oral diclofenac was associated with increased FC levels and that FC returned to normal within 2 weeks of cessation.

The third study reports on a randomized open-label clinical trial and investigates the effect of omeprazole, diclofenac and co-administration of these drugs on FC levels. The findings regarding diclofenac were consistent with those of the second study. Short-term intake of omeprazole alone or when co-administered with diclofenac was associated with increased FC levels. The normalization interval was 3 weeks after cessation.

The fourth study, a prospective cohort study, examines the effect of an acute respiratory tract infection on the FC level. Faecal and salivary calprotectin levels were not found to be increased during respiratory tract infections. This study did not confirm any correlation between calprotectin levels in saliva and faeces during infection.

In conclusion, FC reliably rules out IBD and contradicts the presence of other organic gastrointestinal diseases in patients with gastrointestinal symptoms attending primary care. Patients with a positive FC test together with other symptoms, such as diarrhoea, rectal bleeding, short duration or age >35 years should be prioritized for further investigations. Short-term intake of diclofenac, omeprazole, or their co-administration in healthy individuals is associated with increased FC levels. In patients with an increased FC level on diclofenac, it is sufficient to repeat the FC test 2 weeks after cessation. In patients on omeprazole alone or when co-administered with diclofenac, the FC test should be repeated 3 weeks after cessation. Acute respiratory tract infections were not found to be associated with increased faecal or salivary calprotectin levels.

Abstract [sv]

Patienter med besvär från mag-tarmkanalen utgör en vanlig och diagnostiskt utmanande patientgrupp för allmänläkare. Fekalt kalprotektin (F-kalprotektin) är ett etablerat laboratorieprov för tarminflammation och används för att skilja mellan inflammatorisk tarmsjukdom (IBD) och funktionella mag-tarmsjukdomar. F-kalprotektin misstänks dock kunna öka även av andra orsaker, såsom intag av ickesteroida antiinflammatoriska läkemedel, magsyrahämmande läkemedel eller luftvägsinfektioner. För närvarande saknas tillräckliga kunskaper om i vilken utsträckning dessa faktorer påverkar nivåerna av kalprotektin. För allmänläkare som använder F-kalprotektin som ett diagnostiskt verktyg, är det viktigt att kunna göra en välgrundad värdering av utfallet, så att diagnostik och beslut om behov av vidare utredning kan optimeras.

Syftet med denna avhandling var att undersöka det diagnostiska värdet av F-kalprotektin vid utredning av mag-tarmsjukdomar i primärvården, samt hur nivån av kalprotektin påverkas av viktiga felkällor, såsom intag av vissa anti-inflammatoriska och magsyrahämmande läkemedel. Mer specifikt undersöktes hur oralt diklofenak (icke-steroid antiinflammatoriskt läkemedel), omeprazol (syrahämmande läkemedel) och pågående luftvägsinfektion påverkar nivåerna av F-kalprotektin. För diklofenak och omeprazol utvärderades också tiden för normalisering av F-kalprotektin efter utsättning av preparaten.

I första delstudien granskades totalt 1293 patientjournaler från patienter som lämnade prov för analys av F-kalprotektin i primärvården i Östergötlands län under 2010. En högre andel patienter med positivt test diagnostiserades med IBD och andra organiska mag-tarmsjukdomar jämfört med patienter med negativt test. Hos patienter med symtom från mag-tarmkanalen hade F-kalprotektin ett högt negativt prediktivt värde för IBD, vilket innebär att ett negativt värde med hög sannolikhet utesluter sjukdomen. Patienter med förhöjt F-kalprotektin och samtidig diarré, blödning från ändtarmen, varaktighet <3 månader eller ålder >35 år bör genomgå en prioriterad utredning eftersom sannolikheten för organisk mag-tarmsjukdom är hög. Det diagnostiska värdet av F-kalprotektin har visat sig kunna bli påverkat vid intag av icke-steroida antiinflammatoriska eller syrahämmande läkemedel. Patienter med ett negativt F-kalprotektin, där ingen ytterligare undersökning gjordes, hade inte utvecklat organisk mag-tarmsjukdom vid femårsuppföljningen.

Delstudie 2 och 3 undersökte hur olika felkällor påverkar nivåerna av F-kalprotektin. Intag av läkemedlen diklofenak, omeprazol separat, eller i kombination med varandra under två veckor visade sig orsaka förhöjda nivåer av F-kalprotektin hos friska individer. Värdena återgick till det normala inom två veckor efter utsättning av diklofenak och inom tre veckor efter utsättning av omeprazol eller båda läkemedlen i kombination. Slutsatsen är att hos patienter som har ett förhöjt värde av F-kalprotektin och samtidigt intag av diklofenak eller omeprazol, bör testet upprepas minst 2 respektive 3 veckor efter utsättning för att garantera ett tillförlitligt testresultat.

Den fjärde delstudien undersökte om en akut luftvägsinfektion påverkar F-kalprotektin. Luftvägsinfektioner visade sig inte orsaka förhöjda nivåer av F-kalprotektin. Inget samband påvisades mellan kalprotektin i saliv och i avföring under pågående infektion.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2023. p. 69
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1817
Keywords
Calprotectin, Inflammatory bowel disease, Gastrointestinal disease, Primary health care, Non-steroidal anti-inflammatory agents, Proton pump inhibitors, Respiratory tract infection
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-197024 (URN)10.3384/9789179294014 (DOI)9789179294007 (ISBN)9789179294014 (ISBN)
Public defence
2023-09-18, Belladonna, Building 511, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2023-08-18 Created: 2023-08-18 Last updated: 2023-08-18Bibliographically approved

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Falk, MagnusGrodzinsky, EwaWahlin, KarlKechagias, StergiosHjortswang, Henrik

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