3.15 The impact of smoking on treatment of disease

Last updated: March 2015
Suggested citation: Hurley, S, Greenhalgh, EM & Winstanley, MH. 3.15 The impact of smoking on treatment of disease. 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/3-15-smoking-and-complications-in-medical-treatmen


3.15.1 Surgery

Smoking increases the risk of postoperative complications. Smokers' higher prevalence of chronic diseases, impaired pulmonary reserve, altered immune responses and impaired wound healing are thought to cause such complications. Poorer surgical outcomes result.1 Anaesthesia

The effectiveness of a number of commonly used anaesthetic drugs is reduced in smokers. Higher doses are therefore required. These drugs include opioids,2 neuromuscular blocking agents and some of the volatile agents that are administered by inhalation (via a mask or tracheal tube). The polycyclic aromatic hydrocarbons in cigarette smoke induce the liver enzymes that metabolise anaesthetics, at least partly accounting for these effects.3 Smoking does however decrease postoperative nausea and vomiting, possibly because of the increased metabolism of volatile anaesthetics.3

Smoking increases the risk of intraoperative and postoperative respiratory complications, including bronchospasm, aspiration, hypoventilation and hypoxaemia.4-6 An increased risk for smokers of admission to intensive care after general or orthopaedic surgery has been reported,4 and was attributed to smokers' higher perioperative pulmonary complication rate.

The Australian and New Zealand College of Anaesthetists recommends that patients who smoke be encouraged to quit at any time before surgery.7  The optimal timing of smoking cessation has been a source of controversy, though there is agreement that longer quitting is best.7 Research suggests that recent quitters are no worse off than continuing smokers in terms of pulmonary complications.  (see Section, 9 Postoperative complications

Smoking delays wound healing after surgery. Complications such as infection,10 dehiscence (bursting of sutures)11 and erosions (destruction of tissue surfaces) are increased.12, 13

Such smoking-associated complications are particularly problematic after plastic and reconstructive surgery, orthopaedic surgery (see Section 3.13.2), bowel surgery, dental surgery (see Section 3.11.4), microsurgery and organ transplantation.14–15

For example, after breast reconstruction, smoking has been associated with a doubling of the risk of complications (such as mastectomy flap necrosis or infection) and a five-fold increase in the risk of implant failure.17 Such poor surgical outcomes have led to a call for caution when undertaking breast reconstruction in smokers.18 Similarly, impaired wound healing and wound infection in smokers undergoing breast reduction surgery19, 20 have led to a suggestion that perioperative smoking cessation be an essential eligibility criterion for this surgery.20

Specific post-surgical complications linked with smoking include: a higher failure rate for oral mucosa graft urethroplasty;21 worse hearing and the need for repeat operations after ear surgery;22 increased complications post appendicectomy;23 increased mortality after liver transplantation;15 increased kidney transplant rejection;24 and poorer survival after heart transplantation if either the donor was, or the recipient is, a smoker.16, 25 The poorer organ transplantation outcomes in smokers, combined with the high demand for donated organs, have led to suggestions that smokers be given lower priority for organ transplants and debate about the ethics of such a policy.26-28

Smoking has also been implicated (in a report of four cases) as a risk factor for late-onset infection and other complications after facial injection of a filler substance for cosmetic purposes.29

The magnitude of the impact of smoking on perioperative outcomes was studied in a retrospective review of data from more than 500 000 patients in the US who had non-cardiac surgery.30, 31 Information on the 30-day period following surgery was compared for 82 304 current smokers and 82 304 control patients. Current smokers were 40% more likely to die than never smokers. Their risk of major morbidity also increased: the risk of pneumonia doubled, the risk of unplanned intubation almost doubled, and the odds of postoperative ventilation increased by 50%, cardiac arrest by 60%, myocardial infarction by 80%, and stroke by 70%. The risk of superficial and deep infections increased by 30% and 40%, respectively, and sepsis, organ space infections and septic shock were 30% to 50% more likely. The increased perioperative mortality and morbidity were confined to patients who had smoked more than 11 pack-years. Impact of smoking cessation

A meta-analysis published in 2011 reviewed data from randomised trials and observational studies that had compared postoperative complications in smokers and people who quit smoking before surgery. The analysis found that smoking cessation decreases postoperative complications. In the randomised trials, complications were reduced by about 40%. The review found that the longer the period of preoperative smoking cessation, the greater the reduction in complications.32

Another meta-analysis, also published in 2011, investigated the possibility that smoking cessation just before surgery may be harmful (see Section Data from nine studies that had studied the impact of quitting within eight weeks of surgery were combined. The analysis found no increase (or decrease) in overall postoperative complications in recent quitters compared with smokers. Although the study authors suggested that concern about possible adverse effects associated with stopping smoking just before surgery might therefore be unfounded, an accompanying 'Invited Commentary' pointed out that there was significant heterogeneity in the results of the studies that were combined, which was not surprising because some included patients who had quit two to three days before surgery whereas others included patients who had quit eight weeks prior to surgery.8 The commentators affirmed the wisdom of encouraging patients to quit smoking several months prior to surgery, but queried whether clinicians should be reassured that the timing of smoking cessation in anticipation of surgery is immaterial.

A systematic review published in 2012 explored the relationship between short-term preoperative smoking cessation and postoperative complications, and concluded that at least four weeks of abstinence from smoking reduces respiratory complications, and abstinence of at least three to four weeks reduces wound-healing complications. Short-term (less than four weeks) smoking cessation did not appear to increase or reduce the risk of postoperative respiratory complications.33 The Australian and New Zealand College of Anaesthetists recommend that, based on the current available evidence, anaesthetists and surgeons should not be dissuaded from advising patients to quit at any time before surgery.8

3.15.2 Drug interactions and treatment efficacy

Smoking alters the effects of a number of medications (see also Section on interactions with anaesthetics). Doctors and other healthcare workers need to be aware of these interactions when medications are prescribed and also when patients quit smoking, as drug dosages may need to be adjusted.34

Drug interactions fall into two categories: (i) pharmacokinetic interactions, which occur when cigarette smoke alters a drug's metabolism; or (ii) pharmacodynamic interactions, which occur when the physiological effects of cigarette smoke modify the physiological effects of the drug.35, 36

Pharmacokinetic interactions include increased metabolism of caffeine, heparin, warfarin, theophylline, a number of antipsychotic drugs and a number of benzodiazepines. A meta-analysis of the interaction between smoking and warfarin, for example, found that smoking increased warfarin dosage requirements by about 12%.37 Although it is difficult to know which of the estimated 4800 compounds in cigarette smoke cause these interactions, the polycyclic aromatic hydrocarbons are suspected. These hydrocarbons induce liver enzymes (see Chapter 13, Section and thereby hasten the clearance of any drug (or substance) whose metabolism requires the enzymes.35, 36

Pharmacodynamic interactions include: reduced response to corticosteroids in smokers who are asthmatic,39, 40 decreased sedation with benzodiazepines (possibly due to the stimulant effects of nicotine), slowed absorption of sub-cutaneous insulin (possibly due to reduced blood flow to the skin, mediated by nicotine), and an increased risk of cardiovascular adverse effects in women taking oral contraceptives.35, 36

In the above examples, smoking modifies the effects of particular drugs. It has also been hypothesised that bronchodilator drugs (mainly beta-2-agonists), prescribed for people with chronic obstructive pulmonary disease (COPD), may worsen the effects of cigarette smoke. The theory is that bronchodilation improves smoke inhalation, and may increase the deposition of cigarette smoke on the lungs, thereby increasing cardiovascular disease morbidity and mortality. This hypothesis is yet to be tested.41

3.15.3 Cardiovascular disease

As detailed in Section 3.1, smoking causes cardiovascular disease, and generally, if a person continues to smoke after developing cardiovascular disease their prognosis is worse than if they had quit.

For example, a study of more than 18 000 patients with coronary disease who were receiving a statin drug for coronary disease found that over a five-year period those who continued to smoke had about a 50% higher chance of a major cardiovascular event (death, myocardial infarction, stroke or cardiac arrest) than patients who quit.42 Similarly, poorer treatment outcomes have been reported for people who continue to smoke after coronary artery bypass grafting (CABG)43 or a diagnosis of heart failure,44 compared with people who quit.

3.15.4 Cancer

As detailed in Section 3.5, smoking causes numerous cancers. A review has concluded that overall survival is poorer in smokers with cancer. Studies of lung cancer, prostate cancer, cervical cancer, and head and neck cancer were cited.45 All these studies involved radiotherapy, leading to suggestions that radiotherapy is less effective in smokers. Higher irradiation complication rates for smokers in the studies covered by the review, and other studies,46, 47 support this suggestion. The review also found that the risk of secondary primary tumours is increased in smokers, for malignancies that are related to cancer and also for those that are not.45

The review found little information about the impact of smoking on chemotherapy for cancer, but suggested that treatment outcomes are likely to be worse because of the effects of cigarette smoke on immune function, appetite and basal metabolic rate.45

More severe pain has been associated with smoking in patients with cancer,48 and specifically for lung cancer49 and head and neck cancer.50 This may be because of the decreased effectiveness of opioids (due to induction of liver enzymes by components of cigarette smoke) described in Chapter 13, Section , and failure to increase the dose in response.

The 2014 Surgeon General’s report was the first in its series to review the associations between cigarette smoking and health outcomes in cancer patients and survivors. It concluded that smoking causes adverse health outcomes in people with cancer, while cessation improves their prognosis. Smoking increases all-cause mortality and cancer-specific mortality in cancer patients and survivors, and increases the risk for second primary cancers that are caused by cigarette smoking, such as lung cancer. Smoking is also associated with an increased risk of recurrence, poorer response to treatment, and increased treatment-related toxicity.51

A review of smoking cessation interventions in patients with cancer found that interventions increase quit rates but the difference was not statistically significant. Given the benefits of quitting on cancer outcomes, the authors called for research to identify more effective interventions for cancer patients.48

3.15.5 Treatment of infertility including assisted reproduction

As detailed in Section 3.6, women who smoke have reduced fertility and there is emerging evidence that fertility may also be reduced in male smokers. Smoking also has a negative impact on the outcomes of infertility treatment.53 In women participating in assisted reproduction programmes, a meta-analysis found that smoking is associated with lower pregnancy rates, higher chances of miscarriage and of ectopic pregnancy, and a lower probability of a live birth.54

One study found that for couples who smoked (either female, male or both), the risk of not achieving a pregnancy was about twice as high as for non-smokers.55 Female smoking during the period of infertility treatment has been associated with a decreased number of retrieved ova56 and a higher risk of repeated tubal ectopic pregnancies;57 male smoking has been associated with decreased live birth rates.56 Researchers have estimated that women who smoke need up to twice the number of in vitro fertilisation (IVF) cycles to conceive and suggest there is a correlation between the number of smoking years and the risk of not conceiving through IVF.53 Smoking cessation for both women and men is recommended for couples aiming to become pregnant58 and it has been suggested that access to fertility treatment should be conditional on quitting smoking.53

3.15.6 Contraception

As detailed in Section 3.1, smoking causes coronary heart disease, increasing the risk two- to four-fold.1 The 'combined' oral contraceptive pill (which contains the hormone oestrogen) also increases the risk of myocardial infarction two-fold.59 Women who both take the oral contraceptive pill and smoke have a 20-fold increase in the risk of coronary heart disease, compared with non-smokers who are not taking 'the pill'.60 The impact of smoking and the contraceptive pill is therefore 'synergistic', meaning that the risk of disease is multiplicative rather than additive. Heavier smokers have an even higher risk of coronary heart disease.61

Although the newer 'lower dose' versions of the pill may be associated with a lesser risk of developing coronary heart disease, risk is still elevated in smokers. There is insufficient evidence to evaluate the risk profile of the 'third-generation' pills (containing 30 μg or less of ethynyl estradiol and either gestodene or desogestrel) combined with smoking, but clinicians are advised to be wary when prescribing oral contraceptives to smokers aged in their mid-30s and to exercise extreme caution or avoid using them altogether in smokers aged over 40 years.61

In past decades the risk of stroke, particularly subarachnoid haemorrhage, has been significantly higher among smokers using the contraceptive pill. However research published since the 1990s following up women using lower dose pills is conflicting; some studies show increased risk, other studies have shown no significant effect.61

There is some evidence to suggest that the combined contraceptive pill has a higher failure rate in smokers than in non-smokers.60

3.15.7 Other conditions

A meta-analysis published in 2011 found that in patients receiving long-term haemodialysis or peritoneal dialysis, smoking increased the death rate (all-cause mortality) by 65%.62

Relevant news and research

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



1. US Department of Health and Human Services. The health consequences of smoking: a report of the Surgeon General. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2004. Available from: http://www.cdc.gov/tobacco/data_statistics/sgr/index.htm

2. Woodside JJ. Female smokers have increased postoperative narcotic requirements. Journal of Addictive Diseases 2000;19(4):1–10. Available from: http://www.haworthpress.com/store/E-Text/View_EText.asp?a=4&fn=J069v19n04_01&i=4&s=J069&v=19

3. Sweeney B and Grayling M. Smoking and anaesthesia: the pharmacological implications. Anaesthesia 2009;64(2):179–86. Available from: http://www3.interscience.wiley.com/journal/121575043/abstract

4. Moller AM, Maaloe R and Pedersen T. Postoperative intensive care admittance: the role of tobacco smoking. Acta Anaesthesiologica Scandinavica 2001;45(3):345–8. Available from: http://www3.interscience.wiley.com/journal/118965538/abstract

5. Schwilk B, Bothner U, Schraag S and Georgieff M. Perioperative respiratory events in smokers and nonsmokers undergoing general anaesthesia. Acta Anaesthesiologica Scandinavica 1997;41(3):348–55. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9113178

6. Al-Sarraf N, Thalib L, Hughes A, Tolan M, Young V and McGovern E. Effect of smoking on short-term outcome of patients undergoing coronary artery bypass surgery. Annals of Thoracic Surgery 2008;86(2):517–23. Available from: http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T11-4T14Y6K-16-1&_cdi=4877&_user=10&_orig=search&_coverDate=08%2F31%2F2008&_sk=999139997&view=c&wchp=dGLbVlW-zSkWW&md5=2599b7362e9bd6f024ef9edd3feab3f8&ie=/sdarticle.pdf

7. Australian and New Zealand College of Anaesthetists. Statement on smoking as related to the perioperative period. Review PS12 (2007). Melbourne: Australian and New Zealand College of Anaesthetists, 2007. Available from: http://www.anzca.edu.au/resources/professional-documents/documents/professional-standards/professional-standards-12.html

8. Chow CK and Devereaux PJ. The Optimal Timing of Smoking Cessation Before Surgery: Comment on "Smoking Cessation Shortly Before Surgery and Postoperative Complications". Archives of Internal Medicine 2011;171(11):989–90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21403012

9. Myers K, Hajek P, Hinds C and McRobbie H. Stopping smoking shortly before surgery and postoperative complications: a systematic review and meta-analysis. Archives of Internal Medicine 2011;[Epub ahead of print] Available from: http://archinte.ama-assn.org/cgi/content/full/archinternmed.2011.97v1

10. Araco A, Gravante G, Sorge R, Araco F, Delogu D and Cervelli V. Wound infections in aesthetic abdominoplasties: the role of smoking. Plastic and Reconstructive Surgery 2008;121(5):e305–310. Available from: http://www.plasreconsurg.com/pt/re/prs/abstract.00006534-200805000-00045.htm;jsessionid=LX1cvKLdqrlv69R8HlLPKKjXJJRQvmJGznxJLQJYYGvzQFvbZy1W!932896411!181195628!8091!-1

11. Abbas SM and Hill AG. Smoking is a major risk factor for wound dehiscence after midline abdominal incision; case-control study. Australian and New Zealand Journal of Surgery 2009;79(4):247–50. Available from: http://www3.interscience.wiley.com/user/accessdenied?ID=122364626&Act=2138&Code=4719&Page=/cgi-bin/fulltext/122364626/HTMLSTART

12. Araco F, Gravante G, Sorge R, Overton J, De Vita D, Primicerio M, et al. The influence of BMI, smoking, and age on vaginal erosions after synthetic mesh repair of pelvic organ prolapses. A multicenter study. Acta Obstetricia et Gynecologica Scandinavica 2009;88(7):772-80. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19452293

13. Cundiff G, Varner E, Visco A, Zyczynski H, Nager C, Norton P, et al. Risk factors for mesh/suture erosion following sacral colpopexy. American Journal of Obstetrics and Gynecology 2008;199(6):688 e1–5. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0002-9378(08)00810-7

14. Australian and New Zealand College of Anaesthetists. Statement on smoking as related to the perioperative period. Review PS12 (2007). Melbourne: Australian and New Zealand College of Anaesthetists, 2007. Available from: http://www.anzca.edu.au/resources/professional-documents/documents/professional-standards/professional-standards-12.html

15. Leithead J, Ferguson J and Hayes P. Smoking-related morbidity and mortality following liver transplantation. Liver Transplantation 2008;14(8):1159–64. Available from: http://www3.interscience.wiley.com/cgi-bin/fulltext/121358287/PDFSTART

16. Arora S, Aukrust P, Andreassen A, Simonsen S, Gude E, Grov I, et al. The prognostic importance of modifiable risk factors after heart transplantation. American Heart Journal 2009;158(3):431–6. Available from: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19699867

17. McCarthy C, Mehrara B, Riedel E, Davidge K, Hinson A, Disa J, et al. Predicting complications following expander/implant breast reconstruction: an outcomes analysis based on preoperative clinical risk. Plastic & Reconstructive Surgery 2008;121(6):1886–92. Available from: http://www.plasreconsurg.com/pt/re/prs/abstract.00006534-200806000-00002.htm;jsessionid=LVLGDPrp2BnPy2Mmj4GQLXggJRl2pPDFcLRVFbh2JMn43x1vTY27!982088527!181195629!8091!-1

18. Padubidri A, Yetman R, Browne E, Lucas A, Papay F, Larive B, et al. Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers. Plastic & Reconstructive Surgery 2001;107(2):342–9. Available from: http://lib.bioinfo.pl/pmid:11214048

19. Bartsch R, Weiss G, Kästenbauer T, Patocka K, Deutinger M, Krapohl B, et al. Crucial aspects of smoking in wound healing after breast reduction surgery. Journal of Plastic, Reconstructive & Aesthetic Surgery 2007;60(9):1045–9. Available from: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7XNJ-4N74JF2-8&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=a7fa0121f8317e38ffca36d80b1d2ae7

20. Bikhchandani J, Varma S and Henderson H. Is it justified to refuse breast reduction to smokers? Journal of Plastic, Reconstructive & Aesthetic Surgery 2007;60(9):1050–4. Available from: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7XNJ-4NSPW85-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=8ae7d4d8802e2027d266e6dab42a8a0e

21. Sinha R, Singh V and Sankhwar S. Does tobacco consumption influence outcome of oral mucosa graft urethroplasty? Urology Journal 2010;7(1):45–50. Available from: http://www.urologyjournal.org/index.php/uj/article/view/574/430

22. Kaylie D, Bennett M, Davis B and Jackson C. Effects of smoking on otologic surgery outcomes. Laryngoscope 2009;119(7):1384-90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19418530

23. Lindström D, Sadr Azodi O, Adami J, Bellocco R, Linder S and Wladis A. Impact of body mass index and tobacco smoking on outcome after open appendicectomy. British Journal of Surgery 2008;95(6):751–7. Available from: http://www3.interscience.wiley.com/cgi-bin/fulltext/118639075/PDFSTART

24. Nogueira J, Haririan A, Jacobs S, Cooper M and Weir M. Cigarette smoking, kidney function, and mortality after live donor kidney transplant. American Journal of Kidney Diseases 2010;55(5):907-15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20176427

25. Tsao C, Chen R, Chou N, Ko W, Chi N, Yu H, et al. The influence of donor characteristics on survival after heart transplantation. Transplantation Proceedings 2008;40(8):2636–7. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0041-1345(08)01076-2

26. Bright R. Denial of hepatic transplantation on the basis of smoking: is it ethical? Current Opinion in Organ Transplantation 2010;15(2):49-53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20154621

27. Ehlers S. Ethical analysis and consideration of health behaviors in organ allocation: focus on tobacco use. Transplantation Reviews 2008;22(3):171–7. Available from: http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B75B4-4SBRTJV-2-3&_cdi=12972&_user=10&_orig=browse&_coverDate=07%2F31%2F2008&_sk=999779996&view=c&wchp=dGLbVtz-zSkzV&md5=4e4b3ce5b52ef1f96c0d94f1f8b44ce4&ie=/sdarticle.pdf

28. Sharkey K and Gillam L. Should patients with self-inflicted illness receive lower priority in access to healthcare resources? Mapping out the debate. Journal of Medical Ethics 2010;36(11):661-5. Available from: http://jme.bmj.com/content/early/2010/09/03/jme.2009.032102.long

29. Goldan O, Garbov-Nardini G, Regev E, Orenstein A and Winkler E. Late-onset infections and granuloma formation after facial polylactic acid (New-Fill) injections in women who are heavy smokers. Plastic & Reconstructive Surgery 2008;121(5):e336–8. Available from: http://www.plasreconsurg.com/pt/re/prs/abstract.00006534-200805000-00082.htm;jsessionid=LX1JQZT7pbk10S2NC3pTHHDRQd2L1dFTMMrSQTgZbV1czpKJK1QH!982088527!181195629!8091!-1

30. Turan A, Mascha E, Roberman D, Turner P, You J, Kurz A, et al. Smoking and perioperative outcomes. Anesthesiology 2011;[Epub ahead of print[Available from: http://journals.lww.com/anesthesiology/Abstract/publishahead/Smoking_and_Perioperative_Outcomes.99256.aspx

31. Katznelson R and Beattie W. Perioperative smoking risk. Anesthesiology 2011;[Epub ahead of print] Available from: http://journals.lww.com/anesthesiology/Citation/publishahead/Perioperative_Smoking_Risk.99257.aspx

32. Mills E, Eyawo O, Lockhart I, Kelly S, Wu P and Ebbert JO. Smoking Cessation Reduces Postoperative Complications: A Systematic Review and Meta-analysis. American Journal of Medicine 2011;124(2):144–54 e8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21295194

33. Wong J, Lam DP, Abrishami A, Chan MT, and Chung F. Short-term preoperative smoking cessation and postoperative complications: a systematic review and meta-analysis. Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2012; 59(3):268-279. Available from: http://link.springer.com/article/10.1007/s12630-011-9652-x#page-1

34. Schaffer SD, Yoon S and Zadezensky I. A review of smoking cessation: potentially risky effects on prescribed medications. Journal of Clinical Nursing 2009;18(11):1533–40. Available from: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2702.2008.02724.x/abstract

35. Benowitz N. Drug therapy: pharmacologic aspects of cigarette smoking and nicotine addiction. New England Journal of Medicine 1988;319(20):1318–30. Available from: http://content.nejm.org/cgi/content/brief/319/20/1318

36. Kroon LA. Drug interactions with smoking. Am J Health Syst Pharm 2007;64(18):1917–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17823102

37. Nathisuwan S, Dilokthornsakul P, Chaiyakunapruk N, Morarai T, Yodting T and Piriyachananusorn N. Assessing evidence of interaction between smoking and warfarin: a systematic review and meta-analysis. Chest 2011;139(5):1130–9. Available from: http://chestjournal.chestpubs.org/content/139/5/1130.long

38.  US Department of Health and Human Services. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease. A report of the US Surgeon General, Atlanta, Georgia: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010. Available from: http://www.surgeongeneral.gov/library/tobaccosmoke/report/index.html

39. Ahmad T, Barnes PJ and Adcock IM. Overcoming steroid insensitivity in smoking asthmatics. Current Opinion in Investigational Drugs 2008;9(5):470–7. Available from: http://www.biomedcentral.com/1472-4472/9/470

40. Braganza G, Chaudhuri R and Thomson N. Treating patients with respiratory disease who smoke. Therapeutic Advances in Respiratory Disease 2008;2(2):95–107. Available from: http://tar.sagepub.com/cgi/reprint/2/2/95

41. van Dijk W, Heijdra Y, Scheepers P, Lenders J, van Weel C and Schermer T. Interaction in COPD experiment (ICE): a hazardous combination of cigarette smoking and bronchodilation in chronic obstructive pulmonary disease. Medical Hypotheses 2010;74(2):277–80. Available from: http://www.ncbi.nlm.nih.gov/19800175

42. Frey P, Waters D, Demicco D, Breazna A, Samuels L, Pipe A, et al. Impact of smoking on cardiovascular events in patients with coronary disease receiving contemporary medical therapy (from the Treating to New Targets [TNT] and the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] trials). American Journal of Cardiology 2011;107(2):145–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21129718

43. Lindsay GM, Tolmie EP, Martin WM, Hutton IM and Belcher PR. Smoking after coronary artery bypass: high three-year mortality. Thoracic and Cardiovascular Surgeon 2009;57(3):135–40. Available from: http://www.thieme-connect.com/ejournals/html/thoracic/doi/10.1055/s-2008-1039271

44. Conard M, Haddock C, Poston W and Spertus J. The impact of smoking status on the health status of heart failure patients. Congestive Heart Failure 2009;15(2):82–6. Available from: http://www3.interscience.wiley.com/user/accessdenied?ID=122324641&Act=2138&Code=4719&Page=/cgi-bin/fulltext/122324641/HTMLSTART

45. Gritz ER, Dresler C and Sarna L. Smoking, the missing drug interaction in clinical trials: ignoring the obvious. Cancer Epidemiology Biomarkers & Prevention 2005;14:2287–93. Available from: http://cebp.aacrjournals.org/content/14/10/2287.full.pdf

46. Sauter E, Westgate S and Templemire J. Skin necrosis in cigarette smokers receiving partial breast irradiation: two case reports. Cases Journal 2008;1(1):230. Available from: http://www.casesjournal.com/content/pdf/1757-1626-1-230.pdf

47. Zevallos J, Mallen M, Lam C, Karam-Hage M, Blalock J, Wetter D, et al. Complications of radiotherapy in laryngopharyngeal cancer: effects of a prospective smoking cessation program. Cancer 2009;115(19):4636-44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19569250

48. Bastian L. Pain and smoking among cancer patients: the relationship is complex but the clinical implication is clear. Pain 2011;152(1):10–1. Available from: http://www.painjournalonline.com/article/PIIS0304395910006500/fulltext

49. Daniel M, Keefe F, Lyna P, Peterson B, Garst J, Kelley M, et al. Persistent smoking after a diagnosis of lung cancer is associated with higher reported pain levels. Journal of Pain 2009;10(3):323–8. Available from: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WKH-4VR3PHJ-4&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=023816b4442c522df6d19faa5fc0671b

50. Logan H, Fillingim R, Bartoshuk L, Sandow P, Tomar S, Werning J, et al. Smoking status and pain level among head and neck cancer patients. The Journal of Pain 2010;11(6):528-34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20015696

51. US Department of Health and Human Services. The health consequences of smoking - 50 years of progress. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. Available from: http://www.surgeongeneral.gov/library/reports/50-years-of-progress/

52. Cox LS, Africano NL, Tercyak KP and Taylor KL. Nicotine dependence treatment for patients with cancer. Cancer 2003;98(3):632–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12879483

53. Dondorp W, de Wert G, Pennings G, Shenfield F, Devroey P, Tarlatzis B, et al. Lifestyle-related factors and access to medically assisted reproduction. Human Reproduction 2010;25(3):578–83. Available from: http://humrep.oxfordjournals.org/content/25/3/578.full.pdf

54. Waylen A, Metwally M, Jones G, Wilkinson A and Ledger W. Effects of cigarette smoking upon clinical outcomes of assisted reproduction: a meta-analysis. Human Reproduction Update 2009;15(1):31–44. Available from: http://humupd.oxfordjournals.org/content/15/1/31.long

55. Klonoff-Cohen H, Natarajan L, Marrs R and Yee B. Effects of female and male smoking on success rates of IVF and gamete intra-Fallopian transfer. Human Reproduction 2001;16(7):1382–90. Available from: http://humrep.oxfordjournals.org/cgi/content/full/16/7/1382

56. Fuentes A, Munoz A, Barnhart K, Midwife B, Diaz M and Pommer R. Recent cigarette smoking and assisted reproductive technologies outcome. Fertility and Sterility 2010;93:189-95. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18973890

57. Weigert M, Gruber D, Pernicka E, Bauer P and Feichtinger W. Previous tubal ectopic pregnancy raises the incidence of repeated ectopic pregnancies in in vitro fertilization-embryo transfer patients. Journal of Assisted Reproduction and Genetics 2009;26(1):13-17. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19020971

58. Barbieri RL. The initial fertility consultation: recommendations concerning cigarette smoking, body mass index, and alcohol and caffeine consumption. American Journal of Obstetrics and Gynecology 2001;185(5):1168–73. Available from: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W9P-45SR5B8-40&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_version=1&_urlVersion=0&_userid=10&md5=3513a812898f93109316929b2526c6fc

59. Keeling D. Combined oral contraceptives and the risk of myocardial infarction. Annals of Medicine 2003;35:413-18. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14572165

60. British Medical Association Board of Science and Education & Tobacco Control Resource Centre. Smoking and reproductive life. The impact of smoking on sexual, reproductive and child health. London: British Medical Association, 2004. Available from: http://www.bma.org.uk/ap.nsf/Content/SmokingReproductiveLife

61. US Department of Health and Human Services. Women and smoking. A report of the US Surgeon General. Atlanta, Georgia: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2001. Available from: http://www.cdc.gov/tobacco/data_statistics/sgr/sgr_2001/index.htm

62. Liebman S, Lamontagne S, Huang L, Messing S and Bushinsky D. Smoking in dialysis patients: a systematic review and meta-analysis of mortality and cardiovascular morbidity. American Journal of Kidney Diseases 2011;58(2):257–65. Available from: http://www.ajkd.org/article/S0272-6386%2811%2900810-9/fulltext