3.9 Increased susceptibility to infection in smokers

Last updated: March 2015 
Suggested citation: Bellew, B, Greenhalgh, EM & Winstanley, MH. 3.9 Increased susceptibility to infection in smokers. In Scollo, MM and Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2015. Available from http://www.tobaccoinaustralia.org.au/3-9-increased-susceptibility-to-infection-in-smoke


Inhaling the complex chemical mixture of combustion compounds in tobacco smoke causes adverse health outcomes through mechanisms that include DNA damage, inflammation and oxidative stress.1 Smoking has substantial adverse effects on the immune system, both locally (such as in the respiratory tract and soft tissues in the lungs) and throughout the body. As a result, smokers are at increased risk of a wide range of infections.2, 3 This chapter examines the evidence with respect to acute infections, pneumococcal and meningococcal disease, tuberculosis, complications among persons with existing HIV infection, as well as some other viral and bacterial infections. Evidence regarding periodontitis is covered in Section 3.11.1 and surgical infection is discussed in Section 3.15.1. Chronic respiratory conditions such as chronic obstructive pulmonary disease and asthma are covered in Section 3.2.

3.9.1 Acute respiratory infections

Evidence suggests that there is a causal relationship between smoking and acute respiratory illnesses, as well as all major respiratory symptoms among adults.1 Upper respiratory tract infections (URI or URTI) are the illnesses caused by an acute infection. This involves the upper respiratory tract: nose, sinuses, pharynx or larynx and commonly includes tonsillitis, pharyngitis, laryngitis, sinusitis, otitis media and the common cold.4

Cigarette smoking is a major risk factor for acute respiratory tract infections, with both active and passive smoke exposure increasing the risk of infection.3, 5 Smoking increases the incidence, duration and/or severity of respiratory viral infection.6 The mechanism of this enhanced susceptibility is multifactorial and includes alteration in structural and immune defences—a substantial report of immunologic effects of cigarette smoking was published in 2004; it described the harmful effects on cell counts and distribution in peripheral blood and lung fluids as well as impairment of the functioning of white blood cells, lymphocytes (natural killer cells) and humoral immune system function (production of antibodies).3 Recent studies provide additional detail of the adverse effects on the immune system, such as those on the retinoic acid-inducible gene I (RIG-I),7 inflammatory factors in nasal lavage fluids (NLF IL-6)8, NF-kappaB regulation (regulation of critical defence genes)9, pulmonary T-cell responses10, type II interferon responses (antiviral mechanisms) in airway epithelial cells6, and the functioning of intelectin 1 (an immune defence protein).11 There is also evidence that cigarette smokers have distortions to the normal microbial communities of the upper respiratory tract, which are thought to contribute to the prevalence of respiratory tract complications in this population.12

The patient problems most commonly managed overall by Australian general practitioners are respiratory related (accounting for 22 problems per 100 encounters in 2009–10) and this category also comprises the majority of new problems presented by patients (39% of all problems, managed at a rate of 59 per 100 encounters).13 Cigarette smokers get more colds and worse colds, have much higher rates (several-fold higher) and more severe cases of influenza infection and are at increased risk of bacterial pneumonia compared with non-smokers.3, 5

3.9.2 Chronic respiratory infections

For discussion of chronic respiratory diseases associated with infection such as chronic bronchitis and chronic obstructive pulmonary disease (COPD), see Section 3.2.5.

3.9.3 Pneumococcal and meningococcal disease

Pneumonia is an infection of the lungs, usually caused by bacteria or viruses. Bacteria and viruses living in the nose, sinuses or mouth may spread to the lungs; a person may also breathe some of these germs directly into the lungs. The most common cause of pneumonia in adults is infection with Streptococcus pneumoniae (pneumococcus). Viruses are a common cause of pneumonia, especially in infants and young children. Atypical pneumonia (sometimes called 'walking pneumonia') is caused by bacteria such as Legionella pneumophila, Mycoplasma pneumoniae, or Chlamydophila pneumoniae. Pneumocystis jiroveci pneumonia is sometimes seen in people whose immune system is impaired (due to AIDS or to certain medications that suppress the immune system). Staphylococcus aureus, Moraxella catarrhalis, Streptococcus pyogenes, Neisseria meningitidis, Klebsiella pneumoniae, or Haemophilus influenzae are other bacteria that can cause pneumonia.14

Exposure to tobacco smoke suppresses the activation of the innate immune system response to bacterial infection; this mechanism is considered important in people's susceptibility to pneumonia.15, 16 Evidence from several studies confirms that smoking is significantly associated with the development of bacterial pneumonia.5, 17 There is a dose–response relationship between the current number of cigarettes smoked per day, pack-years of smoking and time since quitting and invasive pneumococcal disease, with approximately 50% of those with invasive pneumococcal disease being cigarette smokers.18

Cigarette smoking is an especially prominent risk factor for pneumococcal pneumonia in patients with chronic obstructive pulmonary disease, but even without COPD, smoking remains a major risk factor. There are reported estimates of increased risk for pneumococcal pneumonia among smokers ranging from an almost two-fold (OR 1.88; 95% CI, 1.11–3.19) to a four-fold increase in risk (OR 4.1; (95% CI, 2.4–7.3) for active smoking. Exposure to secondhand smoke has been found to more than double the risk of this infection (OR 2.5; 95% CI, 1.2–5.1) compared with non-exposed non-smokers.3 A recent review indicates active smoking19 and a recent case–control study indicates secondhand smoke exposure20 as factors that predispose the elderly population to pneumonia. Evidence from several longitudinal studies conducted in large populations confirms significantly increased pneumonia associated mortality in smokers compared with non-smokers (other evidence to date from cross sectional and meta-analytic studies is inconsistent).2 There is also strong evidence that smoking is an independent risk factor for Legionnaires disease, an atypical pneumonia that usually develops two to 14 days after exposure to Legionella pneumophila.17, 21

Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis (also called meningococcus). The meningococcal bacteria (Neisseria meningitidis) are a significant cause of disease in Australia, especially in the very young, teenagers, young adults and those with medical risk factors. The meningococcal bacteria can cause meningitis (inflammation of the meninges, the membrane lining of the brain and spinal cord) and/or septicaemia (blood poisoning). Meningococcal disease is an uncommon but life-threatening infection. There are 13 different types of meningococcal bacteria with the most common in Australia being meningococcal group B and C.22 Notifications of meningococcal disease in Australia for 2006–2007 were at average annual rate of 7.0/100 000 population.23 Neisseria meningitidis remains a major cause of bacterial meningitis and other invasive bacterial infections worldwide with major fluctuations in the incidence of endemic disease and the occurrence of outbreaks and epidemics.24 There is evidence from case–control studies that tobacco smoke exposure independently increases the risk of developing meningococcal disease.2, 25 Children under 18 years of age are at almost four times the risk of infection from maternal smoking (OR 3.8; 95% CI, 1.6–8.9). All age groups have more than a doubling of risk from active smoking (OR 2.4; 95% CI, 0.9–6.6) or from exposure to secondhand smoke (OR 2.5; 95% CI, 0.9–6.9). There is a dose–response relationship between exposure to secondhand smoke and the risk of meningococcal disease in all age groups.25

3.9.4 Tuberculosis

Tuberculosis is an infectious disease caused by various strains of mycobacteria but usually by Mycobacterium tuberculosis. It typically attacks the lungs but can also affect other parts of the body. Approximately one-third of the human population is skin test positive for the infection and is thus thought to harbour the bacterium. The infectious bacilli are inhaled as droplet nuclei that have been exhaled into the atmosphere. These droplets are small enough to remain airborne for several hours. Estimations of the minimum infectious dose range from a single bacterium upwards. In developed countries, tuberculosis is held in check by effective public health systems; in countries where the disease is truly endemic, control remains a huge challenge and one that is exacerbated as highly drug-resistant strains continue to evolve.26 Tuberculosis results in an estimated 1.7 million deaths each year and the worldwide number of new cases (more than nine million) is higher than at any other time in history.27 Overall, Australia has one of the lowest incidence rates of tuberculosis in the world; however it has a relatively high incidence rate among Indigenous people. In 2007 the crude incidence rate was 5.4 cases per 100 000 population but the rate among Indigenous people (6.6/100 000) was more than seven times that in the non-Indigenous Australian-born population (0.9/100 000). The incidence rate for Indigenous people in the Northern Territory was 32.2 per 100 000 population, 13 times that in the non-Indigenous Australian-born population. Looking at tuberculosis rates in countries with a comparable Indigenous population, Australia has a similar rate ratio between the Indigenous and non-Indigenous populations compared with New Zealand and the US and a much lower rate ratio compared with Canada. There are no grounds for complacency given the probability of ongoing transmission of tuberculosis as well as the obvious need to address the ongoing inequalities.28

The US Surgeon General’s report in 2014 was the first in its series to address the evidence regarding smoking and tuberculosis. It concluded that smoking causes both an increased risk of Mycobacterium tuberculosis disease and mortality from tuberculosis, and is associated with higher rates of recurrent tuberculosis. More evidence is needed to determine whether active smoking causes tuberculosis infection, although the report notes that both active and passive smoking are risk factors.29

Other reviews confirm that active smoking is a risk factor for infection and that it increases the risk of progression to tuberculosis disease and death.30,31 Up to one in five deaths from tuberculosis could be avoided if patients were not smokers.32–34 As with active smoking, exposure to secondhand tobacco smoke is also a risk factor for the development of tuberculosis,35 especially for children.30 Quitting smoking and prevention of exposure to secondhand smoke are both important measures in the control of tuberculosis.17 These measures are underscored by the earlier comments about incidence rates among Indigenous people, given that smoking prevalence is markedly higher in this community than in the non-Indigenous population.36

3.9.5 Risks for and complications of HIV

The authors of a recent systematic review suggested that smoking may be an independent risk factor for acquiring HIV infection37 but this finding remains controversial.2 Research into the association between smoking and HIV disease progression has produced inconsistent findings.38 One recent North American study of more than 2000 people living with HIV/AIDS found that current smokers (HR 1.8; 95% CI, 1.3–2.3) and individuals with an increased dose and/or duration of smoking were at greater risk of all-cause mortality compared to never smokers.39 Among people with HIV, smoking may compound the risk of developing COPD, and increase the risk of cervical cancer (in those who also have human papil¬lomavirus; HPV) and liver cancer.29 A review concluded that social class, intravenous drug use and compliance with highly active antiretroviral treatment (HAART) are factors that may interact with smoking behaviour, and the independent role of these factors may be difficult to assess in relation to the outcome of HIV infection.2

3.9.6 Other viral infections

Smoking may also have indirect adverse outcomes such as the increased risk of hepatocellular carcinoma (cancer of the liver) due to the potential smoking-related progression of chronic viral hepatitis.2

3.9.7 Infections of reproductive organs

A small but growing number of research studies deal with the association between cigarette smoking and infections of reproductive organs. Bacterial vaginosis, although often asymptomatic, can cause considerable discomfort and is associated with the development of more serious infections, such as septicaemia and increased risk of poor pregnancy outcome. A recent review found that tobacco smoking is significantly correlated with bacterial vaginosis, typically being in the region of twice as common in smokers as non-smokers, with a greater prevalence noted in young women. Tobacco use was also independently associated with a higher prevalence of specific sexually transmitted bacterial infections—chlamydia and gonorrhoea.17

Persistent infection with oncogenic human papilloma virus (HPV), leading to precancerous lesions and potentially cervical cancer, is a serious health burden.40 Cancer-causing HPV infections can result from interactions of the virus, the host, and many other cofactors; a recent prospective study found that smoking may induce impaired antibody response among HPV-infected young women. Non-smokers were five times more likely to develop HPV antibodies than young (<30 years old) female smokers (OR 0.2; 95% CI, 0.0–0.9). In addition these younger female smokers had a significantly decreased tendency of maintaining constant HPV antibody positive status by the end of the follow-up compared with non-smokers, who were 10 times more likely to do so (OR 0.1; 95% CI, 0.0–0.8).41

3.9.8 Periodontitis

(See Dental 3.11.1.)

3.9.9 Surgical infections

(See 3.15.1.)

3.9.10 Other bacterial infections

There is evidence that smoking may cause an increased risk of peptic ulcer disease owing to an increased rate of Helicobacter pylori infection.2 There is mixed evidence on the relationship between active smoking, bacteraemia (bloodstream infections) and sepsis (a severe illness in which the bloodstream is overwhelmed by bacteria) with about half of studies recently reviewed finding an adverse effect (a positive association).2

Relevant news and research

For recent news items and research on this topic, click here.(Last updated September 2019)


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2. Huttunen R, Heikkinen T and Syrjanen J. Smoking and the outcome of infection. Journal of Internal Medicine 2011;269(3):258-69. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2010.02332.x/pdf

3. Arcavi L and Benowitz N. Cigarette smoking and infection. Archives of Internal Medicine 2004;16:2206-16. Available from: http://archinte.ama-assn.org/cgi/content/full/164/20/2206

4. Eccles MP, Grimshaw JM, Johnston M, Steen N, Pitts NB, Thomas R, et al. Applying psychological theories to evidence-based clinical practice: identifying factors predictive of managing upper respiratory tract infections without antibiotics. Implementation Science 2007;2:26. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17683558

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7. Wu W, Patel K, Booth J, Zhang W and Metcalf J. Cigarette smoke extract suppresses the RIG-I initiated innate immune response to influenza virus in human lung. American Journal of Physiology - Lung Cellular and Molecular Physiology 2011;[Epub ahead of print]. Available from: http://ajplung.physiology.org/content/early/2011/02/18/ajplung.00267.2010.full.pdf+html

8. Noah T, Zhou H, Monaco J, Horvath K, Herbst M and Jaspers I. Tobacco smoke exposure and altered nasal responses to live attenuated influenza virus. Environmental Health Perspectives 2011;119(1):78-83. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20920950?dopt=Citation  

9. Manzel LJ, Shi L, O'Shaughnessy PT, Thorne PS and Look DC. Inhibition by cigarette smoke of nuclear factor-kappaB-dependent response to bacteria in the airway. American Journal of Respiratory Cell and Molecular Biology 2011;44(2):155-65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20348206

10. Feng Y, Kong Y, Barnes PF, Huang FF, Klucar P, Wang X, et al. Exposure to cigarette smoke inhibits the pulmonary T-cell response to influenza virus and Mycobacterium tuberculosis. Infection and Immunity 2011;79(1):229-37. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20974820

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13. Britt H, Miller G, Charles J, Henderson J, Bayram C, Pan Y, et al. General practice activity in Australia 2009–10. General practice series no. 27, cat. no. GEP 27. Canberra: Australian Institute of Health and Welfare, 2010. Available from: http://www.aihw.gov.au/WorkArea/DownloadAsset.aspx?id=6442472722&libID=6442472703

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16. Baqir M, Chen C, Martin R, Thaikoottathil J, Case S, Minor M, et al. Cigarette smoke decreases MARCO expression in macrophages: implication in Mycoplasma pneumoniae infection. Respiratory Medicine 2008;102(11):1604-10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18590957

17. Bagaitkar J, Demuth DR and Scott DA. Tobacco use increases susceptibility to bacterial infection. Tobacco Induced Diseases 2008;4(1):12. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=19094204

18. Nuorti JP, Butler JC, Farley MM, Harrison LH, McGeer A, Kolczak MS, et al. Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. The New England Journal of Medicine 2000;342(10):681-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10706897

19. Fung HB and Monteagudo-Chu MO. Community-acquired pneumonia in the elderly. American Journal of Geriatric Pharmacotherapy 2010;8(1):47-62.

20. Loeb M, Neupane B, Walter SD, Hanning R, Carusone SC, Lewis D, et al. Environmental risk factors for community-acquired pneumonia hospitalization in older adults. Journal of the American Geriatric Society 2009;57(6):1036-40. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1532-5415.2009.02259.x/pdf

21. Ginevra C, Duclos A, Vanhems P, Campese C, Forey F, Lina G, et al. Host-related risk factors and clinical features of community-acquired legionnaires disease due to the Paris and Lorraine endemic strains, 1998-2007, France. Clinical Infectious Diseases 2009;49(2):184-91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19508168

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