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Chrohn's disease: aspects of epidemiology, clinical course, and faecal calprotectin
Örebro University, School of Health Sciences.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The overall aim of this thesis was to study epidemiological and clinical changes in the natural history of Crohn’s disease, its phenotype, the need for surgery and pharmacological therapy over time, as well as the role of faecal calprotectin as a biomarker of pathophysiology and disease course.

An increased incidence and prevalence of Crohn’s disease was seen in the period 1963-2010. The proportion of patients with non-stricturing, non-penetrating disease behaviour at diagnosis increased, suggesting that either patients with Crohn’s disease are diagnosed earlier in their disease course today or that the Crohn’s disease phenotype is changing.

A decrease in complicated disease behaviour, an increased use of immunomodulators, and a reduced frequency of surgical procedures five years after Crohn’s diagnosis was observed. The decrease in surgery at five years seemed to be explained mainly by a decrease in early surgery within three months from diagnosis, likely reflecting an increased proportion of patients with non-stricturing, non-penetrating disease. This suggests that the introduction of new treatment alternatives alone does not explain the reduction in surgery rates, and an increasing proportion of patients with uncomplicated disease at diagnosis may also play an important role.

Subclinical mucosal inflammation, mirrored by increased NFkB activity and increased neutrophil activity (i.e. FC and MPO expression), was observed in healthy twin siblings in both discordant monozygotic and discordant dizygotic twin pairs with IBD. These findings strongly support the hypothesis of an ongoing subclinical mucosal inflammation at the molecular level in healthy first-degree relatives of IBD patients.

Baseline FC as well as consecutive FC measurements predict relapse in IBD. The doubling of FC value increased the risk of relapse by 101% in the following three months. This increased risk attenuates with time by 20% for every three month period since the sample was obtained.

Place, publisher, year, edition, pages
Örebro: Örebro university , 2016. , 97 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 141
Keyword [en]
Crohn’s disease, epidemiology, faecal calprotectin
National Category
Family Medicine Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-49436ISBN: 978-91-7529-135-2 (print)OAI: oai:DiVA.org:oru-49436DiVA: diva2:913361
Public defence
2016-06-02, Universitetssjukhuset, Wilandersalen, Södra Grev Rosengatan, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2017-10-17Bibliographically approved
List of papers
1. Temporal trends in non-stricturing and non-penetrating behaviour at diagnosis of Crohn's disease in Örebro, Sweden: a population-based retrospective study
Open this publication in new window or tab >>Temporal trends in non-stricturing and non-penetrating behaviour at diagnosis of Crohn's disease in Örebro, Sweden: a population-based retrospective study
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2014 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 12, 1653-1660 p.Article in journal (Refereed) Published
Abstract [en]

Background and aim: The incidence of Crohn's disease (CD) is continuing to rise in several countries and in others it appears to have already levelled off after a period of increase. We updated our previous population-based study, by re-extraction of all information on patients diagnosed with CD between 1963 and 2010. Our aim was to assess temporal trends in incidence, prevalence and disease phenotype at diagnosis.

Methods: Patients of all ages with a potential diagnosis of CD were identified retrospectively by evaluation of medical notes of all current and previous patients at the colitis clinic, Örebro University Hospital amended by computerised search in the inpatient, outpatient, primary care and histopathological records. Diagnosis was confirmed by subsequent evaluation of medical notes. Disease phenotype was defined according to the Montreal classification.

Results: The incidence increased over time, especially among Crohn's disease, A1 and A3. SaTScan model revealed a statistically significant high incidence during 1991-2010 (p=0.0001). The median age at diagnosis increased from 28 (3-79) years to 37 (5-87) years (p=0.0002). The point prevalence increased from 21/10(5) (14-32) in 1965 to 267/10(5) (244-291) in 2010. Non-stricturing and non-penetrating disease at diagnosis increased from 12.5% in 1963-1965 to 82.3% in 2006-2010 (p<0.0001).

Conclusion: The incidence of CD increased over time, although it seemed to be plateauing during the most recent decades. A striking increase in non-stricturing, non-penetrating disease at diagnosis was observed, suggesting earlier diagnosis or phenotypic change. The observed point prevalence in 2010 is among the highest reported.

Keyword
Crohn's disease; Epidemiology; Incidence; Phenotype; Prevalence
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-41216 (URN)10.1016/j.crohns.2014.07.006 (DOI)000347019600010 ()25113899 (PubMedID)2-s2.0-84918794564 (Scopus ID)
Funder
Swedish Research Council, 521-2011-2764
Note

Funding Agencies:

Karlskoga Hospital Reseach Foundation AE-37256

Bengt Ihre's Foundation SLS-254051

Örebro University Hospital Research Foundation OLL-256371

Örebro County Research Foundation OLL-93671 OLL-172601 OLL-200541 OLL-256771

Swedish Foundation

Available from: 2015-01-13 Created: 2015-01-13 Last updated: 2017-12-05Bibliographically approved
2. The changing face of Crohn’s disease: a population-based study of the natural history of Crohn’s disease in Örebro, Sweden 1963-2005
Open this publication in new window or tab >>The changing face of Crohn’s disease: a population-based study of the natural history of Crohn’s disease in Örebro, Sweden 1963-2005
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2016 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 3, 304-313 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Changes in medical therapy and surgery might have influenced the natural history Crohn’s disease (CD). Our aim was to explore the short-term outcome of CD and to specifically assess trends in disease phenotype, medications and surgery in the first five years from diagnosis.

Material and Methods: A population-based cohort comprising 472 CD patients diagnosed within the primary catchment area of Örebro University Hospital 1963-2005 were identified retrospectively and described. Data on medication, surgery, progression in disease location and behaviour, were extracted from the medical records. Patients were divided into three cohorts based on year of diagnosis.

Results: The proportion of patients with complicated disease behaviour 5 years after diagnosis decreased from 54.4% (95%CI, 43.9-65.6) to 33.3% (27.4-40.0) in patients diagnosed 1963-1975 and 1991-2005, respectively (p=0.002), whereas the proportion of patients progressing to complicated disease behaviour was stable among those with non-stricturing, non-penetrating disease at diagnosis (p=0.435). The proportion of patients undergoing surgery decreased from 65.8% (55.4-76.0) to 34.6% (28.6-41.5) in patients diagnosed 1963-1975 and 1991-2005, respectively (p<0.001). The reduction in surgery preceded an increased use of immunomodulators and was explained by a decrease in surgery within three months from diagnosis (p=0.001).

Conclusions: We observed a striking decrease in complicated disease behaviour and surgery five years after CD diagnosis, the latter largely due to a decrease in early surgery. Our findings suggest that the introduction of new treatments alone does not explain the reduction in surgery rates, the increasing proportion of patients with inflammatory disease at diagnosis also play an important role.

Place, publisher, year, edition, pages
Oxon, United Kingdom: Taylor & Francis Group, 2016
Keyword
Crohn’s disease, natural history, surgery
National Category
Gastroenterology and Hepatology
Research subject
Epidemiology
Identifiers
urn:nbn:se:oru:diva-46323 (URN)10.3109/00365521.2015.1093167 (DOI)000364484200008 ()26448101 (PubMedID)2-s2.0-84947029986 (Scopus ID)
Funder
Swedish Research Council, 521-2011-2764
Note

Funding Agencies:

Örebro University Hospital Research Foundation OLL-256371

Örebro County Research Foundation OLL-403371  OLL-457731

Available from: 2015-10-28 Created: 2015-10-28 Last updated: 2017-12-01Bibliographically approved
3. Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease
Open this publication in new window or tab >>Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease
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2013 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, no 8, 1725-1731 p.Article in journal (Refereed) Published
Abstract [en]

Background: The mechanisms behind increased fecal calprotectin (FC) in healthy relatives of patients with inflammatory bowel disease (IBD) are unknown. Our aims were to explore if there is a subclinical inflammation with increased neutrophil activity in healthy twin siblings in discordant twin pairs with IBD and to assess the influence of genetics in this context.

Methods: Nuclear factor kappa B (NF-B) and neutrophil activity, based on myeloperoxidase (MPO) and FC, were analyzed in healthy twin siblings in discordant twin pairs with IBD and compared with healthy controls. NF-B and MPO were assessed by immunohistochemistry and FC by enzyme-linked immunosorbent assay.

Results: In total, 33 of 34 healthy twin siblings were histologically normal. Increased NF-B was more often observed in healthy twin siblings in discordant twin pairs with Crohn's disease (13/18 [73%]) and with ulcerative colitis (12/16 [75%]) than in healthy controls (8/45 [18%]). MPO was more often increased in healthy twin siblings in discordant pairs with Crohn's disease (12/18 [67%]) than in healthy controls (11/45 [24%]) and FC more often in healthy twin siblings in discordant pairs with ulcerative colitis (14/21 [67%]) than in healthy controls (6/31 [19%]). Interestingly, the observed differences remained when healthy monozygotic and dizygotic twin siblings were analyzed separately.

Conclusions:We observed increased NF-B, MPO, and FC in healthy twins in both monozygotic and dizygotic discordant pairs with IBD. These novel findings speak for an ongoing subclinical inflammation with increased neutrophil activity in healthy first-degree relatives.

Place, publisher, year, edition, pages
Philadelphia, USA: Lippincott Williams & Wilkins, 2013
Keyword
Inflammatory bowel disease, twins, genetics, subclinical activity, nuclear factor-kappa B, myeloperoxidase, F-calprotectin
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-33716 (URN)10.1097/MIB.0b013e318281f2d3 (DOI)000329363800019 ()23669399 (PubMedID)2-s2.0-84884574092 (Scopus ID)
Funder
Swedish Research Council
Note

Funding Agencies:

Bengt Ihre's foundation  

Nanna Svartz' foundation  

Orebro University Hospital Research Foundation  

Orebro County Research Foundation  

Swedish Foundation for Gastrointestinal research

Available from: 2014-02-12 Created: 2014-02-12 Last updated: 2017-12-06Bibliographically approved
4. Prognostic significance of faecal calprotectin in patients with inactive inflammatory bowel disease
Open this publication in new window or tab >>Prognostic significance of faecal calprotectin in patients with inactive inflammatory bowel disease
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(English)Manuscript (preprint) (Other academic)
National Category
Family Medicine Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-50326 (URN)
Available from: 2016-05-16 Created: 2016-05-16 Last updated: 2017-10-17Bibliographically approved

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