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?
I BD… a complex phenotype
Environmental factors in IBD flora stress smoking IBD drugs hygiene (OC, NSAID) diet appendectomy infections (refined sugar, fat, fast food, corn flakes, chocolate, coca- (measles, mycobacterium, cola, toothpaste) pharyngitis, tonsillitis,)
Disease susceptibility Leone V J Gastroenterol 2013
Developed hygiene?
Developed hygiene? Urban environment and risk of CD (and UC) IRR CD : 1.42, 95%CI: 1.26-1.60 IRR UC : 1.17, 95%CI: 1.03-1.32 Soon BMC Gastroenterology 2012
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? „ Studies are inconsistent and subject to important methodological limitations . „ Riordan AM Eur J Clin Nutr 1998;52:229-38.
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 - NHS study 30-55 yrs at inclusion! Ananthakrishnan Gut 2013 july
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?! NHS study „ For each food item, a commonly used portion size was specified and 30-55 yrs participants were asked how often they consumed the food on an average over the past year. ”?? at inclusion! Ananthakrishnan Gastro 2013 aug
Vitamin D Data are increasing on the immunologic role of vitamin D, particularly on the innate immune system ?? Ananthakrishnan Gastroenterology 2012
… and there is a seasonal variation in vitamin D levels? Bours PH Osteoporosis Int 2011
Is it the then sunlight? or vitamin D? CD risk Nerich V Aliment Pharm Ther 2011
Season of Birth and risk of IBD? Shaw SY CGH 2013 aug
NSAID use? An EPIC IBD in the elderly? BUT: age at inclusion and capture of Aspirin use? Chan SS Aliment Pharm Ther 2011
NSAID dose and duration? NHS study 30-55 yrs at inclusion! + dose +duration of use Anathakrishnan Ann Intern Med 2012
Oral contraceptive use OR CD : 1.44, OR CD : 1.51, (14 studies) 95%CI: 1.12-1.86 95%CI: 1.17-1.96 OR UC : 1.29, NHS study in CD 95%CI: 0.94-1.77 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 Godet PG Gut 1995, Cornish JA Am J GE 2008, Khalili GUT 2013
Hormone replacement therapy and risk of postmenopausal IBD NHS study 30-55 yrs at inclusion! Khalili Gastroenterology 2012
Appendectomy and risk of UC 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) Rutgeerts NEJM 1994 Koutrobakis IBD 2002
Appendicits? and risk of UC Frisch M BMJ 2009
Life events Lerebours E IBD 2007
Smoking
current vs never smoking 1.76 95%CI: 1.40-2.22 P <0.001 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 0.58 95%CI: 0.45-0.75 P <0.001 former vs never smoking 1.79 95%CI: 1.37-2.34 P <0.001 Mahid SS Mayo Clin Proc 2006
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? Finland Denmark (n=577627) Hviid A Gut 2011 Virta E Am J Epidemiol 2012
And, of course there is interaction... Smoking cessation and composition of intestinal microflora cessation non-smoker smoker Biederman PLOS One 2013
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 % without complicated disease % without stricture Aldhous M. Am J GE 2007
Association between smoking, azathioprine/biological use and need for surgery in patients with Crohn`s disease 1,0 no IM / no smoking censored IM / no smoking censored no IM / smoking censored IM / smoking censored 0,8 Survival without surgery 0,6 0,4 0,2 0,0 0,00 50,00 100,00 150,00 200,00 250,00 300,00 follow-up (months) pLogRank<0.001, pBreslow<0.001 Szamosi T EJGH2010
Association between smoking and colectomy in UC OR: 0.57 (95%CI: 0.38-0.85) Cosnes J Best Pract Res Clin GE 2004
Association between smoking and colectomy in UC 1,0 0,8 Survival without colectomy 0,6 0,4 0,2 no-smoking censored 0,0 smoking censored 0,00 100,00 200,00 300,00 400,00 follow-up (months) Szamosi T EJGH2010 pLogRank=0.042, pBreslow=0.08
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 Ideal place to live! appendicits!
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