Environmental exposure: can we reduce risk? Dr Peter Lakatos, - - PowerPoint PPT Presentation

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

• f 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

• f 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 % without stricture % without complicated disease

Association between smoking, azathioprine/biological use and need for surgery in patients with Crohn`s disease

follow-up (months)

300,00 250,00 200,00 150,00 100,00 50,00 0,00

Survival without surgery

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)

400,00 300,00 200,00 100,00 0,00

Survival without colectomy

1,0 0,8 0,6 0,4 0,2 0,0 censored 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!