Influence of environmental factors on the onset and course of inflammatory bowel disease

Table 1 Environmental factors and onset of inflammatory bowel disease - meta-analyses

Author	Study setting	Effect on CD	Effect on UC	Effect on IBD overall
Soon et al[63], 2012	Urban living and risk of CD and UC	IR (incident rate ratio, 1.42; 95%CI: 1.26-1.6)	IR (incident rate ratio, 1.17; 95%CI: 1.03-1.32)
Luther et al[70], 2010	H. pylori infection and risk of IBD, (23 studies)			DR (RR = 0.64; 95%CI: 0.54-0.75)
Barclay et al[50], 2009	Breast feeding and early onset IBD (7 studies)	NA	NA	DR (OR = 0.69; 95%CI: 0.51-0.94)
Jones et al[42], 2008	Prenatal or childhood passive smoking and risk of IBD (13 studies)	NA	NA
Cornish et al[54], 2008	OCP and risk of IBD (14 studies)	IR (RR = 1.46 ; 95%CI: 1.26-1.70)	IR (RR = 1.28 ; 95%CI: 1.06-1.54)
Mahid et al[37], 2007	Smoking and risk of IBD (13 studies related to UC and 9 related to CD)	IR with current smoking (OR = 1.76; 95%CI: 1.40-2.22)	DR with current smoking (OR = 0.58; 95%CI: 0.45-0.75)
			IR with former smoking (OR = 1.79; 95%CI: 1.37-2.34)

IR: Increased risk; DR: Decreased risk; NA: No association; CD: Crohn’s disease; UC: Ulcerative colitis; RR: Relative risk; IBD: Inflammatory bowel disease; OCP: Oral contraceptive pill.

Table 2 Environmental factors and onset of inflammatory bowel disease - cohort studies

Author	Study subjects	Effect on CD	Effect on UC
Timm et al[76], 2014, Europe	Population-based cohort	DR with being born and living on livestock farm for first 5 yr of life
	10864 subjects from ECRHS1 cohort
	Outcome - place of upbringing and risk of IBD
Khalili et al[53], 2013, United States	146681 subjects from NHS I and II	NA - Breastfeeding, low or high birth weight, preterm birth	NA - Breastfeeding, low or high birth weight, preterm birth
	3373726 person-years of follow-up
	Outcome - risk of IBD in adulthood
Ananthakrishnan et al[31], 2013, United States	170776 subjects from NHS I and II	DR - Long term intake of higher dietary fibre especially from fruit	NA with dietary fibre
	3317425 person-years of follow-up
	Outcome - diet and risk of IBD in adulthood
Ananthakrishnan et al[84], 2013, United States	152461 subjects from NHS I and II	IR with recent and baseline depressive symptoms	NA with recent and baseline depressive symptoms
	1787070 person-years of follow-up
	Outcome - Depressive symptoms and risk of IBD
Levi et al[75], 2013, Israel	Cohort of 953684 Jewish adolescents	IR with high socioeconomic status, western origin, male sex
	Outcome - sociodemographic factors and risk of IBD	DR with four or more children in childhood
Higuchi et al[38], 2012, United States	229111 subjects from NHS I and II	IR - Current smoker, former smoker	NA - Current smoker
	Outcome - Smoking and risk of IBD		IR - Former smoker
Ananthakrishnan et al[56], 2012, United States	76795 subjects from NHS I	IR - frequent use of NSAID	IR - frequent use of NSAID
	1295317 person-years of follow-up
	Outcome - NSAID and aspirin exposure and risk of IBD	NA - Aspirin	NA - Aspirin
Ananthakrishnan et al[48], 2012, United States	72719 subjects from NHS	DR - Higher predicted level of plasma Vitamin D	NA - Vitamin D level in plasma
	1492811 person-years of follow-up
	Outcome - Vitamin D and risk of IBD

¹European Community Respiratory Health Survey. IR: Increased risk; DR: Decreased risk; NA: No association; CD: Crohn’s disease; UC: Ulcerative colitis; RR: Relative risk; IBD: Inflammatory bowel disease; NSAID: Nonsteroidal anti-inflammatory drug; NHS: Nurses Health Study.

Table 3 Environmental factors and onset of inflammatory bowel disease - case control studies

Author	Study setting	Effect on CD	Effect on UC
Ng et al[51], 2014, Asia Pacific	CD - 186	DR with breast feeding for > 12 mo, antibiotic use, having dogs, daily tea intake, daily physical activity	DR with breast feeding for > 12 mo, antibiotic use, daily tea and coffee intake, presence of hot water tap, flushing toilet in childhood
	UC - 256		IR with smoking
	Controls - 940
	Outcome - environmental risk factors and IBD
Sood et al[64], 2014, India	UC- 518		IR with owning a pet and stressful events
	Controls - 188		DR with better toilet facilities and having private bed
	Outcome - environmental risk factors and UC
Chu et al[62], 2013, South Africa	CD - 88	DR - Helminth infection, shared housing, raw beef consumption	DR - Helminth infection, mixed race, smoking, shared housing, raw beef consumption
	UC - 63	IR - Urban dwelling, parental tertiary education	IR -parental tertiary education
	Control - 219
	Outcome - childhood risk factors and IBD
Jakobsen et al[114], 2013, Denmark	CD - 59	IR with bedroom sharing, prior hospitalisation with gastrointestinal infection, family history	IR with prior hospitalisation with gastrointestinal infection, family history
	UC - 56	DR with wholemeal bread consumption	DR with daily vegetable consumption
	Controls - 477 Outcome - environmental risk factors and pediatric IBD
Hlavaty et al[52], 2013, Slovakia	CD - 190	IR with short duration of breast feeding, infrequent childhood sports activity, smoking, infrequent contact with animals in childhood	IR with short duration of breast feeding, infrequent childhood sports activity, smaller family size in childhood
	UC - 148
	Controls - 355
	Outcome - environmental risk factors and IBD
Pugazhendhi et al[45], 2012, India	CD - 200	IR with safe drinking water
	Controls - 200 Outcome - environmental risk factors and CD	DR with regular fish consumption and presence of cattle in house
Castiglione et al[115], 2012, Italy	CD - 468	NA with any factors except IR with smoking and appendectomy	NA with any factors except DR with smoking and appendectomy
	UC - 527
	Controls - 562
	Outcome - environmental risk factors and CD
Hansen et al[44], 2011, Denmark	CD - 123	DR with breast feeding, tonsillectomy,	DR with breast feeding, tonsillectomy, appendectomy, smoking
	UC - 144		IR with pertussis and polio vaccine, measles infection, low fibre and high sugar
	Controls - 267
	Outcome - environmental risk factors and IBD	IR with pertussis and polio vaccine, measles infection, smoking, low fibre and high sugar
López-Serrano et al[61], 2010, Spain	124 CD and 235 controls	IR - Living in urban area, high educational level, social status	IR - Living in urban area, high educational level, social status
	146 UC and 278 controls	DR - Childhood respiratory infection and gastroenteritis	DR - Childhood respiratory infection and gastroenteritis, appendectomy, current smoking
	Outcome - onset of IBD
Gearry et al[39], 2010, New Zealand	Population-based case-control study	IR with smoking, high social class at birth, Caucasian ethnicity	IR with high social class at birth, Caucasian ethnicity, migrant
	CD - 638, UC - 653, Controls - 600 Outcome - risk factors and IBD	DR with breastfeeding and childhood vegetable garden	DR with smoking, breast feeding and childhood vegetable garden
Joseph et al[28], 2009, India	CD - 34	IR - lower levels of Vitamin D
	Controls - 34
	Outcome - vitamin D and CD
Amre et al[32], 2007, Canada	CD - 130	DR - higher consumption of vegetables, fruit, fibre, fish, long chain omega three fatty acid
	Controls - 202
	Outcome - diet and pediatric CD
Baron et al[116], 2005, France	CD - 222	IR - Family history, Breast feeding, BCG vaccination, history of eczema	IR - Family history, disease during pregnancy, bedroom sharing
	UC - 60	DR - Regular drinking of tap water	DR- Appendectomy
	Matched controls
	Outcome - pediatric onset IBD

IR: Increased risk; DR: Decreased risk; NA: No association; CD: Crohn’s disease; UC: Ulcerative colitis; RR: Relative risk; IBD: Inflammatory bowel disease.

Table 4 Environmental factors and course of inflammatory bowel disease

Author	Study setting	Effect on CD	Effect on UC
Ott et al[89], 2014, Germany	Cohort study	IR of EIM	NA
	CD - 161
	UC - 96
	Outcome - Smoking and EIM
Feagins et al[101], 2014, United States	Case-control study	NA with NSAID, antibiotics, stress, smoking, infection and travel in past 3 mo
	Active IBD - 166
	IBD in remission - 68
	Outcome - triggers for flare of IBD
Ananthakrishnan et al[97], 2013, United States	Multi-institutional cohort study, CD - 5405, UC - 5429	IR of surgery with psychiatric comorbidity	NA of surgery with psychiatric comorbidity
	Outcome - psychiatric comorbidity and surgery and hospitalisation in CD and UC
Bernstein et al[93], 2010, Canada	Population-based cohort	IR of flare - High perceived stress
	IBD - 704	NA with flare - NSAID, antibiotics, non-enteric infection
	Outcome - risk factors for flare
	Follow-up - 1 yr
Packer et al[110], 2010	Systematic review, 7 studies	Physical activity significantly increased quality of life and decreased disease activity
	Outcome - Physical activity and course of IBD
Bitton et al[95], 2008, Canada	Cohort study,	IR with stress/avoidance coping, higher CRP, fistulising disease behaviour, disease confined to the colon
	101 patients with CD in remission
	Outcome - biopsychosocial factors and relapse
	Follow-up - 1 yr
Takeuchi et al[25], 2006, United Kingdom	Case series	IR of flare with non-selective NSAID
	IBD - 209
	Outcome - risk of flare with NSAID
Sandborn et al[100], 2006, United States	RCT - Celecoxib vs placebo for 2 wk		No significant difference between celecoxib (3%) and placebo group (4%)
	UC - 222
	Outcome - exacerbation during 2 wk
Persoons et al[96], 2005, Belgium	Cohort study	Major depressive disorder associated with reduced response to infliximab
	CD - 100
	Outcome - major depressive disorder and response to infliximab
Cosnes et al[103], 1999, France	Cohort study	NA between OCP use and disease flare
	CD - 331
	Outcome - OCP and flare of CD
	Follow-up -12 to 18 mo
Cosnes et al[87], 1999, France	Cohort study	IR of flare - Current smokers
	CD - 622	NA with flare - Obesity, dyslipidemia and alcohol consumption
	Outcome - risk factors for flare of CD
	Follow-up -12 to 18 mo
Boyko et al[117], 1998, United States	UC - 209, compared smokers with non-smokers		DR of hospitalisation
	Outcome: Smoking and course of UC		NA with colectomy rates

IR: Increased risk; DR: Decreased risk; NA: No association; CD: Crohn’s disease; EIM: Extraintestinal manifestation; IBD: Inflammatory bowel disease; NSAID: Nonsteroidal anti-inflammatory drug; RCT: Randomised controlled trial, CRP: C reactive protein, OCP: Oral contraceptive pill.