Cigarette Smoking Linked to Antibody-Associated Vasculitis

Pathogenic mechanism between respiratory exposures and the development of AAV could be established in future research.

Greg McDermott, PhD

Smoking cigarettes is associated with antibody-associated vasculitis (AAV), especially myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-positive AAV, study findings show.

Greg McDermott, MD, of the Department of Medicine at Massachusetts General Hospital and Harvard Medical School, and a team of Boston-based investigators examined the association between cigarette smoking and AAV. They compared a consecutive inception cohort of 484 patients with diagnosed AAV from 2002-2017 with a cohort of sex-, race-, and age-matched controls.

The team identified cases from patients who were evaluated and treated at Partners HealthCare. AAV diagnoses were systematically confirmed by manual medical chart review using a consensus algorithm. All of the patients included were PR3-ANCA or MPO-ANCA positive.

Never smoking was defined as <100 cigarettes smoked in a patient’s lifetime. Smoking status at the time of treatment initiation was used to determine former or current smoking status. The team determine a cumulative smoking exposure in pack years by calculating the product of years smoked and average packs of cigarettes smoked per day.

Cases and controls were assigned to groups based on cumulative lifetime smoking exposure: never smokers, 0-20 pack years, 21-40 pack years, 41-60 pack years, and >60 pack years of smoking.

The team used conditional logistic regression to examine the association between cigarette exposure and AAV.

Among the 484 patients with AAV, 11 were excluded because they did not have the proper smoking status information documented. McDermott and the team matched 472 AAV cases to 1419 controls from the Partners Biobank.

The mean age for cases and controls was 59 years old—59% of both cases and controls were women, and 84% of both were white. A majority of participants with AAV (65%) were MPO-ANCA positive. Renal involvement existed in 64% of patients at baseline, while 41% had pulmonary and 46% had head and neck involvement at the index study date.

The mean Birmingham Vasculitis Activity Score/Wegener Granulomatosis score was 4.7.

The proportion of ever smokers was greater among those with AAV (54%) than controls (42%) and smoking was associated with increased odds of having AAV (OR, 1.7; 95% CI, 1.4-2.2). Average pack years of cigarette exposure was 13.1 for AAV cases and 3.5 for controls (P <.001).

After stratification by smoking status, the odds of AAV were higher for former smokers (OR, 1.6; 95% CI, 1.3-2) and current smokers (OR, 2.7; 95% CI, 1.8-4.1) compared with never smokers. There was a strong dose-response that the odds of having AAV rose with increasing pack years of exposure. Those with the greatest pack year exposure (>60 pack years) to cigarette smoking had the greatest odds of having AAV (OR, 30.3; 95% CI, 8.7-105.6) compared to those who never smoked.

The associations were strong among participants with MPO-ANCA-positive disease (former smokers: OR, 1.7; 95% CI, 1.3-2.3; current smokers: OR, 3.5; 95% CI, 2.1-6.1) but not in those with PR3-ANCA-positive AAV (former smokers: OR, 1.3; 95% CI, .9-2; current smokers: OR, 1.7; 95% CI, .8-3.5).

The findings could suggest a possible pathogenic mechanism between respiratory exposures and the development of AAV. Additional research could investigate such a mechanism.

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