Recent Research Probes Smoking & the Risk for Autoimmune Disease

It’s no secret to any health professional, including rheumatologists, that smoking cigarettes or using other tobacco-based products is unhealthy. Yet how does smoking specifically affect rheumatic diseases, and what are some of the newest findings in this area? What role do e-cigarettes have in the smoking risk landscape? Those are the sorts of questions asked by researchers with an interest in this topic.

Zeroing in on RA, Lupus

“I think the main thing to realize is that when inhaled, smoking affects the body’s systems in many ways,” says Albert A. Rizzo, MD, FCCP, FACP, senior medical advisor for the American Lung Association. “Inflammation leads to lung diseases, and unfortunately, that same type of inflammation can occur in the rest of the body.”

The 2014 Surgeon General’s report on smoking links cigarette use to several rheuma­tological diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).¹ It specifically implies a causal relationship between cigarette smoking and RA, but not SLE, and states that cigarette smoking can reduce the effectiveness of tumor necrosis factor-α inhibitors, which are often used to treat autoimmune disease.

The most likely cause for a connection between rheumatological diseases and smoking is a mix of a genetic predisposition and environemental factors—including tobacco use, Dr. Rizzo says.

One interesting correlation is the common presence of lung manifestations, such as nodules, scarring and fibrosis, among patients with RA and Sjögren’s syndrome. “Some of these diseases may manifest in the lungs earlier than the arthritic com­ponents,” Dr. Rizzo says. Whether this connection can be hastened by cigarette smoking is not always clear. Still, “to say the least, it’s a complex interaction,” he says.

Although smoking could potentially affect many types of rheumatological disease, the bulk of research seems to focus on RA and SLE.

“Most of the evidence shows increased inflammatory activities, radiographic changes, and severity of disease in lupus, rheumatoid arthritis and ankylosing spondylitis,” says Richard Lai, MD, FACP, FACR, Great Falls Clinic, Department of Rheumatology, and assistant professor of rheumatology, Idaho College of Osteopathic Medicine, Meridian, Idaho. “Smoking is also postulated as an independent risk factor to trigger the onset of rheumatoid arthritis,” he adds, citing 2014 research.²

“During the last decade or so, accumulating data has consistently demonstrated a strong association between cigarette smoking and rheumatoid arthritis risk, particularly for seropositive RA, with an interaction between smoking and underlying genetics,” says Medha Barbhaiya, MD, MPH, assistant attending rheumatologist and clinical researcher, Hospital for Special Surgery, and assistant professor, Weill Cornell Medical College, New York.

Research obtained from the Nurses’ Health Study found the association of smoking with RA risk appears to be highest among those who smoked greater than 10 pack-years.³ “The risk appeared elevated in past smokers until 20 years after cessation, after which it was similar to that of nonsmokers,” Dr. Barbhaiya says.

Regarding SLE, the Surgeon General’s report found inadequate evidence to infer the presence or absence of a causal relationship between cigarette smoking and SLE or the response to therapy once a patient has lupus.¹ Previous data in patients with SLE have been conflicting, usually because of limited sample sizes, retrospective data and a lack of detailed risk-factor data, says Dr. Barbhaiya. However, some research has found a link between smoking and an increased risk of SLE development, particularly among current smokers, she adds.

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Using the Nurses’ Health Study, Dr. Barbhaiya and Karen Costenbader, MD, along with researchers from Brigham and Women’s Hospital, Boston, also found current—not past—smoking was strongly related to risk for the subtype of SLE associated with anti-double-stranded DNA+.⁴ “The strong and specific association of current smoking with anti-double-stranded DNA seropositive SLE suggest smoking is involved in the pathogenesis of this specific subtype of SLE,” Dr. Barbhaiya says.

Using the Black Women’s Health Study cohort, Drs. Barbhaiya and Costenbader, along with researchers from the Slone Epidemiology Center at Boston University, Boston, also studied the risk of cigarette smoking on SLE development. Their study found that among 59,000 black women, 127 new cases of lupus developed between 1995 and 2015. The risk of SLE was higher by 45% among smokers compared with never smokers; this number did not reach statistical significance. The risk also increased more (not significantly) with a greater number of pack-years of smoking.⁵

Additional studies will help researchers analyze smoking and its effect on rheumatological diseases, says Geeta Nayyar, MD, MBA, rheumatologist and assistant clinical professor of medicine at Florida International University, Miami, and chief innovation officer at TopLineMD.com and Femwell Group Health. “Further studies are needed to analyze the exact effect of smoking on each rheumatic disease separately to really know the sole mechanism of action smoking may have on an individual disease,” she says.

Paradoxical questions are brought on by the research that require further investigation, says Anca D. Askanase, MD, MPH, director and founder, Columbia University Lupus Center, and associate professor of medicine, Division of Rheumatology, Columbia University Irving Medical Center, New York. She points to research that finds smoking increases the risk of psoriatic arthritis (PsA) in the general population but somehow lowers the risk in patients who already have psoriasis. Another confusing finding comes from research indicating a possible protective effect of cigarette smoking for ankylosing spondylitis and RA, Dr. Lai says. However, these findings have been called into question by more recent studies, say Drs. Askanase and Lai.⁶

Benefits that kick in as soon as a person stops smoking include a lower heart rate & a better sense of taste & smell.

How Quitting Helps

Rheumatologists can potentially share information with patients about the benefits that kick in when patients stop smoking, Dr. Rizzo says.

Some of these benefits happen immediately when a person stops. These include a lower heart rate and a better sense of taste and smell. Thinking more long term, the risk for heart disease and other chronic conditions lowers over several years. Fifteen years after a person quits smoking, the risk for heart disease is the same as for a nonsmoker, the Centers for Disease Control and Prevention (CDC) reports.

“Sometimes the tradeoff [with quitting] is increasing weight, but a patient can worry about those extra 10 lbs. later on,” Dr. Rizzo says.

A multi-center, open-label, randomized controlled trial is underway in patients with RA to analyze the effects on disease activity with an intensive smoking cessation program compared with standard care on smoking cessation.⁷ The intensive smoking cessation program will include motivational counseling along with tailored nicotine replacement. The trial will include 150 daily smokers who have RA, but who are in remission or who have low to moderate disease activity, rated by a Disease Activity Score-28 (DAS28) of 5.1 or less. Seventy-five patients will receive the intensive therapy. At three months, researchers will evaluate the patients’ self-reported smoking cessation and achievement of a European League Against Rheumatism (EULAR) clinical response by a DAS28 improvement of 0.6 or greater. Additional follow-ups will take place at three, six and 12 months. The study is slated for completion in June 2019, according to ClinicalTrials.gov.

“Although further studies are needed in this area, the idea that rheumatic disease may be modifiable by behavior change, such as quitting smoking, may provide hope to patients who otherwise feel resigned there is no way to change their disease risk,” Dr. Barbhaiya says.

The Unknowns of E-cigs

Some patients try e-cigarettes. Per advertising, e-cigarettes are potentially safer than regular cigarettes and may even serve as an anti-smoking aid.

However, little is known about the effects of e-cigarettes on the incidence or worsening of rheumatological disease. In fact, little is known about their effects overall.

“There’s a lot of work to be done,” Dr. Rizzo says. “E-cigarettes have flooded the market, and they are very popular among the teen and middle-school crowd,” he says. E-cigarette use is actually more prevalent in this younger age group than regular cigarette use. However, using them could become a gateway for regular cigarettes.

Although advertising may claim e-cigarettes can help people stop smoking, the U.S. Food and Drug Administration (FDA) has found no such product safe and effective in helping smokers quit. The FDA does not approve of e-cigarettes as anti-smoking aids. It also announced in September 2018 action aimed to reduce the amount of e-cigarette advertising geared toward younger people.

The presence of some form of nicotine—albeit a smaller amount—in e-cigarettes, along with other kinds of chemicals, can’t be good for the body and could cause chronic bronchitis, Dr. Rizzo says.

“The body’s reaction to many of the chemicals in traditional cigarette smoke causes long-lasting inflammation, which in turn leads to chronic diseases, like bronchitis, emphysema, and heart disease,” Dr. Nayyar says. “Since e-cigarettes contain many of the same toxic chemicals, there is no reason to believe that they will significantly reduce the risks for these diseases.”

Even if e-cigarettes prove not be entirely dangerous, they still can be highly addictive due to the nicotine in them, Dr. Askanase says. “Additionally, e-cigarette aerosols produced by heating the e-cigarettes are likely to have a negative impact on people’s and teenagers’ health in particular,” she says.

The real risks from e-cigarettes may take 15 to 20 years to become clear, Dr. Nayyar adds.

The ACR does not currently have any recommendations regarding e-cigarette use, Dr. Lai says. However, the CDC says e-cigarettes can be used as an alternative to all forms of smoked tobacco in nonpregnant adult smokers.⁸ The CDC does not recommend that non-smokers start using e-cigarettes; it only suggests them instead of traditional cigarette use.

Prompting Patients to Quit

One consideration in anti-smoking research is how to convince patients of the importance of quitting.

“I always discuss smoking cessation with my patients regardless of if they express interest or not,” Dr. Lai says. Many times, he’ll explain the association of smoking with the rheumatological disease a patient has. He finds most patients are receptive because they are in significant pain.

However, rheumatologists, primary care physicians and other specialists may need to repeat the anti-smoking message several times, Dr. Rizzo says. That’s because most smokers try to quit 10 to 11 times over their lifetime. It’s a hard sell due to the overwhelmingly addictive effect of nicotine.

Dr. Barbhaiya has also observed this challenge. “Although patients are very knowledgeable about the hazardous effects of smoking on [their] general health, the fact remains that it can be very difficult to quit,” she says.

A lack of uniformity among physicians about smoking advice also can complicate the picture. “In half of the departments, most doctors give advice to quit smoking to all or almost all patients with inflammatory diseases. However, very few departments have a specific protocol for smoking cessation,” Dr. Nayyar says.

The American Lung Association has found that a combination of FDA-approved quit smoking medications along with counseling and a patient commitment to stop smoking are most effective, Dr. Rizzo says. 

Vanessa Caceres is a medical writer in Bradenton, Fla.

References

1. U.S. Department of Health and Human Services. Office of the Surgeon General. The Health Consequences of Smoking—50 Years of Progress. 2014; p.584.
2. Di Giuseppe D, Discacciati A, Orsini N, Wolk A. Cigarette smoking and risk of rheumatoid arthritis: A dose-response meta-analysis. Arthritis Res Ther. 2014 Mar 5;16(2):R61.
3. Sparks JA, Chang S-C, Liao KP, et al. Rheumatoid arthritis and mortality among women during 36 years of prospective follow‐up: Results from the Nurses’ Health Study. Arthritis Care Res (Hoboken). 2016 Jun;68(6):753–762.
4. Barbhaiya M, Tedeschi SK, Lu B, et al. Cigarette smoking and the risk of systemic lupus erythematosus, overall and by anti-double stranded DNA antibody subtype, in the Nurses’ Health Study cohorts. Ann Rheum Dis. 2018 Feb;77(2):196–202.
5. Cozier YC, Barbhaiya M, Castro-Webb N, et al. Relationship of cigarette smoking and alcohol consumption to incidence of systemic lupus erythematosus in the Black Women’s Health Study. Arthritis Care Res (Hoboken). 2018 Aug 9. doi: 10.1002/acr.23703. [Epub ahead of print]
6. Gomes JP, Watad A, Shoenfeld Y. Nicotine and autoimmunity: The lotus’ flower in tobacco. Pharmacol Res. 2018 Feb;128:101–109.
7. Roelsgaard IK, Thomsen T, Ostergaard M, et al. The effect of an intensive smoking cessation intervention on disease activity in patients with rheumatoid arthritis: Study protocol for a randomized trial. Trials. 2017 Nov 28;18(1):570.
8. Centers for Disease Control and Prevention. Electronic cigarettes: What’s the bottom line?.