The role of smoking in cancer, lung diseases and cardiovascular diseases is now widely recognised. The fact that smoking also affects the immune system is under-appreciated. In fact, smoking has wide-ranging and severe impacts on the immune system. It increases inflammation levels, increases the risk of allergic conditions, increases the incidence of autoimmune diseases, decreases immune responses to infectious diseases and increases infection rates.1 The 2014 US Surgeon General’s report concluded that components of cigarette smoke have both immune activating and immune-suppressive effects.2
This section describes the effects of smoking on chronic inflammation and autoimmune diseases. See Section 3.9 for a description of how cigarette smoke increases the susceptibility to infection of smokers.
Inflammation
Inflammation is a response of the immune system to a range of stimuli. These include infections, injuries, damage from heat or chemical burns, poisoning, as well as conditions such as autoimmune diseases and atherosclerosis (hardening of the arteries). Inflammation involves an influx of immune cells, usually white blood cells, into an area of damage or infection. Inflammation is a process used to fight infections, clear damage and heal wounds. Counterintuitively, inflammation itself can cause damage, particularly if it continues unresolved for a long period of time.2, 3
Acute (short-term) inflammation usually last for a few days. Causes include injuries and bacterial infections. Chronic inflammation refers to long-term conditions. Often chronic inflammation occurs as an aberration of the immune system, where it inadvertently attacks the body rather than responding to a pathogen or clearing damage. This section discusses chronic inflammatory conditions affected by smoking, particularly autoimmune diseases in which smoking potentially plays a role in causation.
Cigarette smoke has pro-inflammatory effects that trigger an inflammatory response. This occurs both in the lungs and in the rest of the body. The chemicals present in cigarette smoke interact with various different cell types of the immune system, increasing the numbers of cells that accumulate at site of inflammation and changing the levels of cytokines (signalling molecules released by immune cells)1 and other biological molecules that regulate inflammation.2
Autoimmune diseases
Autoimmune diseases are a range of at least 80 conditions in which the immune system attacks the body. In these diseases, an immune response is raised to a healthy part of the person’s own body, rather than to an invading pathogen or an injury. Chronic inflammation is a common symptom for people with autoimmune diseases and leads to damage that causes problems specific to each separate disease. Autoimmune diseases are usually long-term conditions without a cure, however treatments that reduce inflammation can improve quality of life for people suffering many of these conditions. The exact causes—that is, the reasons why the immune system attacks the body—are usually unknown. Many autoimmune diseases involve production of antibodies that recognise parts of the body rather than pathogens.4 These auto-antibodies direct immune responses to damage normal tissues. Another feature of some autoimmune diseases are white blood cells called T-cells that recognise and attack normal cells rather than virally infected cells, their standard target.2
3.17.1 Rheumatoid arthritis
Rheumatoid arthritis is an autoimmune disease characterised by joint inflammation, pain, swelling, stiffness and loss of function. Rheumatoid arthritis most often affects the hand joints and both sides of the body. Many people with rheumatoid arthritis suffer debilitating fatigue which makes it difficult to participate fully in life.5 About 458,000 Australians (1.9% of the total population) have rheumatoid arthritis, based on self-reported data from 2017–2018. The prevalence of this disease is higher for women (2.3%) than men (1.5%).5 A large proportion of patients have the rheumatoid factor (RF) antibody.6 Effective treatments for rheumatoid arthritis are drugs that block the effects of a pro-inflammatory signalling molecule called TNFa.7
Smoking is a cause of rheumatoid arthritis.2 The 2014 US Surgeon General’s report concluded that the evidence is sufficient to infer that cigarette smoking is a cause of rheumatoid arthritis. The risk of developing this disease is between 1.4 and 4-fold higher for smokers than for never smokers.2 The risk is most markedly elevated in people who have the RF antibody.8 Smoking is considered to be the major environmental risk factor for rheumatoid arthritis.9 There have been suggestions that smoking only increases susceptibility to rheumatoid arthritis in individuals who have specific genetic profiles.10
There is strong evidence that smoking leads to poorer responses to drug treatments in patients with rheumatoid arthritis.2, 11 Smoking reduces the effectiveness of TNFa inhibitors, the drugs that relieve symptoms for most people with this disease.2
There is currently insufficient research to determine whether smoking cessation reduces the risk of rheumatoid arthritis.12
3.17.2 Anal abscess and fistula
Anal abscess is an inflammatory disease of the skin around the anus. Inflammation causes sores, or ulcers, to form on the inside wall of the bowel. Those ulcers can extend through the entire thickness of the bowel wall, creating a tunnel (or ‘fistula’) to drain the pus from the infected area through an abscess on the skin on or near the anus. The fistula remains even if the abscess is successfully treated with antibiotics and this is prone to constant inflammation and re-infection.13 A small case–control study of 74 patients with anal abscess/fistula found that smoking within the previous year doubled the risk of this condition.14 Further evidence resulted from a case–control study in 2018. This study of a Chinese population found people with an anal abscess had a 12.3-fold higher odds of a history of smoking compared to people without the condition.15
3.17.3 Graves’ disease
Graves’ disease is an autoimmune disease that affects the thyroid gland, usually leading to an enlargement of the gland and increased production of thyroid hormones. Some symptoms, such as insomnia, weight-loss and sweating, result from the changes in thyroid hormones, whereas symptoms like swelling and complications affecting the eyes are a result of autoimmune inflammation.
Genetic factors account for most of the risk for Graves’s disease, with environmental risk factors accounting for approximately 21% of the risk.16 Smoking is a risk factor for Graves’ disease, but there is currently insufficient evidence to conclude that smoking is a cause. A case–control study from 1993 found that smokers had a 1.9-fold higher odds of developing Grave’s disease than non-smokers.17
Smoking is also a risk factor for a rare complication of Grave’s disease called Graves’ ophthalmopathy. For more details, see Section 3.10.4.
3.17.4 Psoriasis (see Skin 3.14.4)
3.17.5 Systemic lupus erythematosus (see Skin 3.14.5)
3.17.6 Diabetes (see Smoking and Diabetes in Section 3.16)
3.17.7 Multiple Sclerosis
Multiple sclerosis is an autoimmune disease characterised by nerve damage. Smoking is considered a risk factor for multiple sclerosis on the basis of a few studies finding an association between smoking and the disease.18 A 2011 systematic review and meta-analysis used the Bradford Hill criteria for causation to assess the relationship between smoking and multiple sclerosis. Results showed a statistically significant association of smoking with multiple sclerosis and with secondary progression of the disease. People who smoked had a 1.54-fold increased risk of developing multiple sclerosis and a 1.8-fold increase risk of progression compared to non-smokers. The authors concluded that there was strong evidence of a causal role of smoking for the risk of multiple sclerosis, but only moderate evidence for progression, based on the Bradford Hill criteria.19 People with multiple sclerosis who smoke have higher rates of disease activity, faster rates of brain damage, and a greater disability burden. Some of the outcomes of smoking were found to be reversible with cessation.18
3.17.8 Primary biliary cirrhosis
Primary biliary cirrhosis is a rare autoimmune disease of the liver. Numerous studies have shown that smokers are more likely to develop this disease compared to non-smokers.20-22 A systematic review and meta-analysis from 2019 found that the odds of primary biliary cirrhosis for ever smokers was significantly higher than non-smokers (odds ratio of 1.31). Smoking was also associated with an increased risk of more severe disease21, 23 and mortality from this condition.24 For more details, see Section 3.12.3.
3.17.9 Inflammatory Bowel Disease (see Section 3.12.2)
3.17.10 Other autoimmune diseases
There is some evidence of an effect of smoking on other chronic inflammatory and autoimmune disease. However, the evidence is insufficient for making specific conclusions about smoking being an independent risk factor or a cause.
Smoking may be a risk factor for a rare disease called chronic periaortitis (inflammation surrounding the aorta).25 Smoking may also be a risk factor for microscopic colitis, a common cause of chronic, non-bloody diarrhoea.26
Relevant news and research
For recent news items and research on this topic, click here. (Last updated January 2021)
References
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