3.12 Gastro-intestinal diseases

Last updated: May 2020

Suggested citation: Purcell, K. Hurly, S and Greenhalgh E 3.12 Gastro-intestinal diseases. In Greenhalgh EM, Scollo, MM and Winstanley, MH [editors].  Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2020. Available from  http://www.tobaccoinaustralia.org.au/3-12-gastrointestinal-disease

 

3.12.1 Peptic ulcer disease

Mucus and other secretions line the gastrointestinal tract, protecting it from gastric acid. If this protective mechanism is impaired or if there is an increase in gastric acid or other damaging agents, then ulceration may occur. Peptic ulcer disease involves the formation of ulcers in either the lining of the stomach (gastric ulcers) or the duodenum, the section of the small intestine closest to the stomach (duodenal ulcers).

The presence of the gastric bacterium Helicobacter pylori causes infection and damage to the gastrointestinal wall, greatly increasing the risk of developing peptic ulcers. The Helicobacter pylori organism is present in all people with duodenal ulcers and 70–90% of people with gastric ulcers. The risk of developing peptic ulcers is also increased among people who take non-steroidal anti-inflammatory drugs (NSAIDS).

Peptic ulcers were the eleventh most common cause of hospital admissions in Australia in 2007–2008,1 and almost 3% of Australians reported having some sort of peptic ulcer in 2001.2

Smoking increases the risk of peptic ulcer disease in people who are infected with Helicobacter pylori.3 In Australia, about 13% of peptic ulcer disease in men and 9% in women has been attributed to smoking.4

Smoking affects the gastrointestinal tract in several ways: it reduces the production of gastric mucus and other protective secretions, promotes duodenal reflux and reduces blood flow to the lining of the tract. In this compromised environment, Helicobacter pylori may be better able to spread and cause damage.3 Smoking may also be related to an increased risk of developing complications of peptic ulcer disease, such as ulcer perforation or bleeding, but this effect may be confined to people who are not taking NSAIDS.3

The increased risk of peptic ulcer disease consequential to smoking appears to reverse with smoking cessation.3

The higher prevalence of peptic ulcer disease in people with mental disorders has been largely explained by smoking and alcohol dependence in this population.5

3.12.2 Inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of conditions in which the intestines are inflamed. The two major types of IBD are Crohn’s disease and ulcerative colitis. Crohn’s disease can involve any part of the gastrointestinal tract, but most commonly affects the small intestine or the colon. Ulcerative colitis is restricted to the colon and the rectum. The presenting symptoms of these two IBDs are often similar (abdominal pain, vomiting, diarrhoea), but the pathophysiology differs. Crohn’s disease is thought to be an autoimmune disease but ulcerative colitis is not. Tissue inflammation tends to be deeper with Crohn’s disease than with ulcerative colitis. Both conditions are treated with drugs and/or surgery.6, 7

A complex interaction between genetic factors and environmental factors, including smoking, influences the risk and prognosis of inflammatory bowel disease.8-10

The 2014 US Surgeon General’s report conducted a meta-analysis on 24 studies of smoking and Crohn’s disease. Smoking at or before diagnosis was associated with a 1.8-fold increased risk of this disease. The conclusion was that the evidence suggests, but is not strong enough to conclude, causation of Crohn’s disease from smoking. Smoking increases the risk of Crohn’s disease, but more evidence is needed to confirm whether it is a cause.11 Smoking affects the immune system in a variety of ways and it is not clear which of its immunologic effects are relevant to Crohn’s disease.7

(In Australia in earlier reports quantifying the burden of disease published prior to the 2014 US Surgeon General’s report, about 34% of Crohn’s disease in men, and about 36% in women, had been attributed to smoking.12 There was some debate whether the effect of smoking on Crohn’s disease is dose‐dependent.13)

At the time of diagnosis, smokers with Crohn’s disease report a  greater use and greater dependency on corticosteroids compared with non-smokers.14 Patients with Crohn’s disease who continue to smoke also have a worse prognosis and their symptoms are exacerbated compared with non-smokers .15 A 2016 systematic review and meta-analysis of the effects of smoking on the disease course in Crohn's disease confirmed that smokers had increased risks of a recurrence  of disease activity.16 Smokers also have a greater risk of needing intestinal surgery.10,14,16 After surgery, they are more than twice as likely as non-smokers to have a disease recurrence. Smokers have a 2.5-fold increased risk of repeat surgery within 10 years.15 Quitting smoking has a beneficial impact on disease related outcomes.16  

Smokers with both main types of irritable bowel disease appear to be at greater risk of manifesting symptoms of the disease in other parts of the body, including chronic skin disorders and joint problems.17 Following cessation, the risk reduced to that of never smokers between 1 and 2 years after quitting.17

In contrast to its impact on Crohn’s disease, smokers seem to have a decreased risk of ulcerative colitis by about 40% and quitting increases the risk.18 The 2014 Surgeon General’s report concluded that the evidence suggests, but is not sufficient, to conclude that smoking has a protective effect.11 Ex-smokers have an almost 80% higher risk of ulcerative colitis compared with never smokers.18 The reason or reasons for the apparent contradictory effect of smoking on the two main IBDs is unknown.7

Microscopic colitis is also a type of inflammatory bowel disease characterised by watery diarrhoea. It affects the large bowel and can only be diagnosed from a biopsy examined under the microscope. Two large prospective cohort studies of women in the United Kingdom found an association between current smoking and increased risk of microscopic colitis. The risk of microscopic colitis was greatest for heavier smokers (higher pack-years). The risk was  reduced following sustained smoking cessation of five years or more.19  The mechanism by which smoking increases the risk of microscopic colitis is not currently known.19

3.12.3 Disorders of the liver and gallbladder

Smoking adversely affects the hepatobiliary system.

The ‘Million Women Study’ in the UK found that smoking increases the risk of liver cirrhosis two- to three-fold and the risk of gallbladder disease (symptomatic gallstones or cholecystitis) by about 10–30%.20 Ex-smokers were found to have elevated risks for these conditions compared with never smokers, but lower risks than current smokers.

A 2019 meta-analysis of data from 26 prospective studies found that smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer.21

A 2016 systematic review and meta-analysis of 59,530 gallbladder disease cases among 4,213,482 participants found an increased risk of gallbladder disease associated with tobacco smoking. There was a dose-dependent positive association with increasing number of cigarettes smoked per day.22

Large case-control studies in the UK and US have found that smoking increases the risk of primary biliary cirrhosis (now referred to as primary biliary cholangitis) by about 50–60%.23, 24 Primary biliary cholangitis is an autoimmune disease that results in the destruction of hepatic bile ducts. A 2011 meta-analysis of five published studies, that together included almost 2,000 cases of primary biliary cirrhosis, confirmed the association and found that smoking increases risk by almost 70%.25 A 2019 systematic review and meta-analysis of nine case–control studies with 21,577 participants also confirmed that smokers were at greater risk of primary biliary cholangitis than never smokers. It has been suggested that the effect of smoking on the immune system and the cytotoxic effect of cigarettes were possible mechanisms associated with this elevated risk.26 The severity of disease is associated with greater intensity of smoking. For every pack-year increase in smoking intensity, there was a 3.2 times higher likelihood of advanced fibrosis. Smokers with advanced primary biliary cholangitis also had increased mortality rates compared with never smokers.27

Non-alcoholic fatty liver disease (NAFLD) is another important cause of chronic liver disease often associated with obesity and metabolic syndrome. While some large studies have found that smoking is an independent  risk factor for NAFLD,28,29 others have reported that the association between smoking and increased risk of NAFLD only occurred among those who did not drink alcohol.30 There appears to be a dose response association and the incidence of fatty liver disease increases significantly as the number of cigarettes smoked increased.30,31 Smoking also appears to increase the severity of NAFLD, and smokers have a higher risk of liver fibrosis compared with non-smokers.32,33,34 There also appears to be an increased risk of NAFLD associated with exposure to second hand smoke. 35

 See Section 3.17 for a discussion of autoimmune disease.

3.12.4 Disorders of the pancreas

Pancreatitis is inflammation of the pancreas. It can be acute or chronic. The most common symptom is severe abdominal pain. Gallstones cause acute pancreatitis and high alcohol intake is a risk factor for chronic pancreatitis. Smoking increases the risk of gallstones and smoking is also strongly associated with drinking alcohol. It was initially difficult to determine whether smoking per se increases the risk of pancreatitis independently of other risk factors.  However, the association between smoking and pancreatitis is now well-established.36-39

Smoking is associated with an increased risk of acute pancreatitis, an earlier age of onset, and more frequent recurrences of acute pancreatitis.40 Dual use of tobacco and high- risk drinking are associated with increased risk.38,41 Male smokers who consumed more than four drinks per day had a higher  risk of developing pancreatitis compared with never smokers and former smokers.38  The exact mechanism by which smoking increases the risk of pancreatitis is not well understood, although two common metabolites from cigarette smoke, (nicotine and NNK ) have been shown to induce  changes in the pancreas consistent with those seen in pancreatitis.42,43

A cohort study of over 18,000 residents of Copenhagen found that smoking does increase the risk of pancreatitis, independently of its effect on gallstones and its association with alcohol consumption. In fact about 46% of cases of pancreatitis in this group of people were attributed by the researchers to smoking.44 A 2015  meta-analysis of twenty-two studies also  identified a positive association between cigarette smoking with the development of pancreatitis.37

A large population-based prospective study in the United States, confirmed that smoking was an independent risk factor for non-gallstone related pancreatitis, recurrent acute pancreatitis and chronic pancreatitis  in men and women.  Smoking was not associated with gallstone acute pancreatitis in both men and women.38 Another meta-analysis of 12 observational studies had similar findings—that smokers were at greater risk of developing acute pancreatitis but not gallstone related pancreatitis.39 A dose-response effect was observed, with current smokers having a 40% increased risk of acute pancreatitis for every additional 10 cigarettes per day they smoked.39

Another meta-analysis of twelve studies confirmed an association between  smoking and increased risk of acute pancreatitis. The risk is strongest for current smokers, but former smokers had a higher risk compared with never smokers.45 A 2019 systematic review and meta-analysis of ten prospective studies on tobacco smoking and pancreatitis found that current smoking was associated with 49%, 93% and 62%  increases in the relative risk of acute pancreatitis, chronic pancreatitis and acute/chronic pancreatitis combined compared to never smokers. Former smokers showed 24%, 30% and 29% increases in the relative risk compared to never smokers. There was a dose response effect, with an increasing risk for every 10 cigarettes smoked per day and a  an increased risk for every 10 pack-years of smoking.46

Note that pancreatitis may increase the risk of pancreatic cancer, which is one of the malignancies caused by smoking (see Section 3.5.2).3

3.12.5 Other gastrointestinal disorders

Data from an Australian twin study suggest that smoking increases the risk of appendectomy by about 65%, but that this risk decreases by 15% every year after quitting.47 A retrospective survey of more than 6,000 male British construction workers who underwent appendicectomy over a 33-year period found that smoking increased the risk of perforated appendix and also increased the risk of post-operative consultations in non-perforated appendicitis (see Section 3.15).48

The microbiome refers to a community of microbes residing in a location comprising of bacteria, archaea, viruses, fungi, and protozoa, together with their genes and genomes.49 Microbiome has a critical role in the development of healthy immune responses.49 Smoking causes changes to the gut microbiome, leading to various diseases of the gastrointestinal track such as Crohn's disease, ulcerative colitis and cancers. However, the exact causal relationship between smoking and microbiome alterations is still being examined.49 A 2018 study of patients undergoing an upper GI endoscopy found that mucosa-associated microbiota (MAM) of current smokers has reduced bacterial diversity compared with never smokers.50 A population based cross-sectional study of 758 males, also found the bacterial composition of gut microbia among smokers was different to that of never smokers.51 Smoking cessation has some benefits, with bacterial diversity at least partially or fully restored in ex-smokers.50,51

Sessile serrated polyps (SSPs) are associated with the development of colorectal cancer.52,53 A large cross-sectional study from Korea of more than 30,000 adults undergoing colonoscopy included both younger (30–49 years) and older ( 50–75 years) adults. Current smokers in both age groups had an increased risk of SSPs. Heavier smokers (those with the greatest pack-years) were at greater risk of developing SSPs than lighter smokers and never smokers and also had an elevated risk of larger or multiple SSPs.53

A 2016 systematic review and meta-analysis found that tobacco smoking is associated with an increased incidence of diverticular disease and related complications. There was a dose-dependent association with increasing number of cigarettes smoked per day associated with higher risk. There was also some evidence that smoking increases the risk of diverticular disease complications, but the number of relevant studies was small.54

For information about anal fistula, see Section 3.17.2

 

Relevant news and research

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References

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