Cigarette Smoking Linked to Greater Likelihood of MPO-positive AAV

Cigarette smoking significantly increases the odds of developing ANCA-associated vasculitis (AAV), particularly the disease form with antibodies against the myeloperoxidade (MPO) protein, and this risk is stronger in people with greater cigarette exposure, a large database study reported.

The study, “Association of Cigarette Smoking With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis,” was published in the journal JAMA Internal Medicine.

The specific cause of AAV is unknown, although research has indicated that both genetic and environmental factors, including exposure to asbestos or silica, can contribute to its onset.

While cigarette smoking has been shown to increase the risk of many diseases, previous studies evaluating smoking and AAV risk have been inconclusive. This is mostly due to limitations in how those studies were designed, as they had small sample sizes, used inconsistent control groups, and only examined specific variants of AAV, the study said.

Addressing these shortcomings, researchers at Massachusetts General Hospital and Harvard Medical School accessed the extensive records of the Partners HealthCare system, in Boston, to investigate the relationship between smoking and AAV.

A total of 473 patients diagnosed with AAV in the Partners system between 2002 and 2017 were included in the study. For comparison, each AAV patient was matched by age, race, and sex to three people without AAV. The 1,419 individuals in this control group had been in the Partners system, and filled out a smoking questionnaire between January 2010 and May 2018.

Researchers found that the proportion of cigarette smokers in the AAV group (54%) was significantly higher than in the control group (42%), showing that smoking increased by 70% the odds of having AAV.

To clarify the association, they used more specific smoking data, including whether the person was a current or former smoker, and the amount of cigarettes each person smoked.

Compared to people who never smoked in their lives, former smokers and current smokers both had a significantly greater chance of developing AAV, though this effect was greater in current smokers (2.7 times greater vs. 1.6 times for former smokers).

Also, the greater the amount of cigarettes smoked throughout a person’s life, the greater the changes of having AAV, the team noted. For example, while people who smoked one to 19 packs per year were not more likely to develop AAV, those smoking 40 to 59 packs per year were about eight times more likely to have the disease.

This risk reached its highest in people smoking more than 60 packs a year: their odds of having AAV were 30.3 times higher compared to never smokers.

“We observed a dose-response association such that greater cumulative smoking exposure was associated with a greater odds of having AAV,” the researchers wrote.

Interestingly, smoking only significantly increased the odds of having MPO-positive AAV; proteinase 3 (PR3)-positive disease was increased to a lesser extent that did not reach statistical significance in either former or current smokers.

Again, this supports the notion that MPO-ANCA and PR3-ANCA are distinct conditions, characterized by differences in genetic risk, disease mechanisms, and response to treatment.

The association between smoking and AAV was significant in both males and females.

“We observed a strong association between current and former cigarette smoking and the odds of having AAV. These findings expand the list of potential risk factors for AAV, including genetics and silica exposure,” the researchers concluded. “This association was especially strong for patients with MPO-ANCA.”

While data from this study showed that smoking increases the odds of having AAV, further research is necessary to determine the mechanism by which this occurs, they added.