environmental exposure: can we reduce risk? · oxford inflammatory bowel disease masterclass...
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Oxford Inflammatory Bowel Disease MasterClass
Environmental exposure: can we reduce
risk?
Dr Peter Lakatos, Budapest, Hungary
Oxford Inflammatory Bowel Disease MasterClass
Environmental exposure: can
we reduce risk?
Peter Laszlo Lakatos
1st Department of Medicine
Semmelweis University Budapest
Hungary
Objective
to discuss the role of environmental
factors in IBD
•in disease susceptibility
•in predicting disease phenotype
•During the course of the disease
•short-long term prognosis and risk for
complications?
Reducing risk of WHAT?
•disease susceptibility?
•disease phenotype?
•disease course progression?
•AND if we decrease certain risks will we
have to other complications?
IBD… a complex phenotype
Environmental factors in IBD
IBD drugs
(OC, NSAID)
flora
appendectomy diet (refined sugar, fat, fast food,
corn flakes, chocolate, coca-
cola, toothpaste)
hygiene
stress smoking
infections (measles, mycobacterium,
pharyngitis, tonsillitis,)
Disease susceptibility
Leone V J Gastroenterol 2013
Developed hygiene?
Developed hygiene? Urban environment and risk of CD (and UC)
Soon BMC Gastroenterology 2012
IRRCD: 1.42,
95%CI: 1.26-1.60
IRRUC: 1.17,
95%CI: 1.03-1.32
Developed hygiene?
Bernstein CN Am J GE 2006
Developed hygiene?
Bernstein CN Am J GE 2006
Vaccination?
Davis RL Arch Ped Adolesc Med 2001
Villumsen Inflamm Bowel Dis 2013
Diet?
Riordan AM Eur J Clin Nutr 1998;52:229-38.
„Studies are inconsistent and subject to important
methodological limitations. „
Diet: but how to measure?
Hou AJG 2011, Ng Gut 2013
Diet-fat: CD+ UC-
Hou AJG 2011, Ng Gut 2013
Fat intake and UC -
Ananthakrishnan Gut 2013 july
NHS study 30-55 yrs
at inclusion!
Diet: fat and the EPIC
Tjonneland GUT 2009, de Silva GE 2010
IBD in the elderly!
Diet- fruit, vegetable, fiber -?
Hou AJG 2011, g Gut 2013
Fiber intake and CD?!
Ananthakrishnan Gastro 2013 aug
NHS study 30-55 yrs
at inclusion!
„For each food item, a commonly used portion size was specified and
participants were asked how often they consumed the food on an
average over the past year.”??
Vitamin D
Ananthakrishnan Gastroenterology 2012
Data are increasing on the immunologic role of
vitamin D, particularly on the innate immune system
??
… and there is a seasonal
variation in vitamin D levels?
Bours PH Osteoporosis Int 2011
Is it the then sunlight? or vitamin D?
Nerich V Aliment Pharm Ther 2011
CD risk
Season of Birth and risk of IBD?
Shaw SY CGH 2013 aug
NSAID use?
Chan SS Aliment Pharm Ther 2011
An EPIC
IBD in the elderly?
BUT: age at inclusion and capture of Aspirin use?
NSAID dose and duration?
Anathakrishnan Ann Intern Med 2012
NHS study 30-55 yrs
at inclusion!
+ dose
+duration
of use
Oral contraceptive use
Godet PG Gut 1995, Cornish JA Am J GE 2008, Khalili GUT 2013
ORCD: 1.44, ORCD: 1.51, (14 studies)
95%CI: 1.12-1.86 95%CI: 1.17-1.96
ORUC: 1.29,
95%CI: 0.94-1.77 NHS study in CD HR:
2.82 (95% CI 1.65 to 4.82)
among current users
1.39 (95% CI 1.05 to 1.85)
among past users
Hormone replacement therapy
and risk of postmenopausal IBD
Khalili Gastroenterology 2012
NHS study 30-55 yrs
at inclusion!
Appendectomy and risk of UC
Rutgeerts NEJM 1994
Koutrobakis IBD 2002
Rate of appendectomy in UC: 1/174 (0.6%)
Rate of appendecytomy in controls: 41/161 (25.4%)
OR: 59.1 (95% CI, 18-189)
Appendicits? and risk of UC
Frisch M BMJ 2009
Life events
Lerebours E IBD 2007
Smoking
Mahid SS Mayo Clin Proc 2006
1.76
95%CI: 1.40-2.22
P<0.001
current
vs
never smoking
former
vs
never smoking
1.30
95%CI: 0.97-1.76
P=0.08
Mahid SS Mayo Clin Proc 2006
current
vs
never smoking
former
vs
never smoking
0.58
95%CI: 0.45-0.75
P<0.001
1.79
95%CI: 1.37-2.34
P<0.001
Smoking;
is the risk age-dependent?
Lakatos IBD 2013
Air pollution?
Kaplan GG Am J GE 2010
Is it infectious? Virus, bacteria or
worms?
CD: Infections? Antibiotics? Cause or indicator?
Halfvarson Inflamm Bowel Dis 2006
Antibiotics and CD? Indicator or bystander?
Hviid A Gut 2011 Virta E Am J Epidemiol 2012
Finland
Denmark (n=577627)
And, of course there is interaction...
Biederman PLOS One 2013
Smoking cessation
and composition
of intestinal
microflora
cessation non-smoker smoker
Predicting disease phenotype/disease
course?
Is diet predicting the relapse rate in UC?
Jowett SL Gut 2004
Can we modify the disease?
Vitamin D In DSS mouse maybe, in human?
In vitro, 1,25(OH)2D3 increased TEER, TJ proteins and mRNA expressions,
decreased the FITC-D permeability, and preserved structural integrity of the TJ in Caco-2 cells
Zhao H BMC Gastroenterology 2012
Vitamin D level is associated with
activity and QoL
Ulitsky JPEN J Parenter Enteral Nutr 2011
Vitamin D level and hospitlization/surgery predictor or indicator only?
Ananthakrishnan IBD 2013
Is stress associated with disease course in IBD?
Is stress associated with disease course in IBD?
Bitton Gut 2008
Psychiatric co-morbidity and risk of
hospitalization, drug use and surgery?
Ananthakrishnan Aliment Pharm Ther 2013
Smoking is associated with
probability of flares in CD
Cosnes J Gastroenterology 2001
Smoking and disease phenotype in CD
Aldhous M. Am J GE 2007
% w
ith
ou
t st
rict
ure
% w
ith
ou
t co
mp
lica
ted
dis
ease
Association between smoking, azathioprine/biological use
and need for surgery in patients with Crohn`s disease
follow-up (months)
300,00250,00200,00150,00100,0050,000,00
Su
rviv
al w
ith
ou
t su
rgery
1,0
0,8
0,6
0,4
0,2
0,0
censored
censored
censored
censored
IM / smoking
no IM / smoking
IM / no smoking
no IM / no smoking
pLogRank<0.001, pBreslow<0.001
Szamosi T EJGH2010
Association between smoking and colectomy in UC
Cosnes J Best Pract Res Clin GE 2004
OR: 0.57 (95%CI: 0.38-0.85)
Association between smoking and colectomy in UC
pLogRank=0.042, pBreslow=0.08
follow-up (months)
400,00300,00200,00100,000,00
Su
rviv
al w
ith
ou
t co
lecto
my
1,0
0,8
0,6
0,4
0,2
0,0censored
censored
smoking
no-smoking
Szamosi T EJGH2010
Air pollution and hospitalization? Probably not specific for IBD
Ananthakrishnan IBD 2011
Summary: Environmental factors
Molodecky NA, IBD 2011
Modifying evironmental factors?
Ananthakrishnan Curr Gastro Rep 2013
Environmental factors in IBD
• There are many methodological limitations
Molodecky NA, IBD 2011
So, how can we modify the environmental
exposure predisposing to IBD?
•Protective: breastfeeding, vitamin D,
fruit/vegetable, fiber, sunshine
•Avoid: developed hygiene but also early life
gastrointestinal infections/antibiotics, air polution,
NSAID, sugar?/fat?/red meat, stress-life events,
psychiatric co-morbidity, in females: contraceptives-
HRT, in males-do not born April-June (if you are
Canadian?)
•Conflictive: Smoke or not? depending whether you
are afraid of CD or UC?, have an appendectomy,
but only before the age of 20 yrs and only for
appendicits! Ideal place to live!