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Original Investigation
April 13, 2020

Association of Cigarette Smoking With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Author Affiliations
  • 1Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston
  • 2Clinical Epidemiology Program, Massachusetts General Hospital and Harvard Medical School, Boston
  • 3Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston
  • 4Mongan Institute; all at Massachusetts General Hospital and Harvard Medical School, Boston
JAMA Intern Med. 2020;180(6):870-876. doi:10.1001/jamainternmed.2020.0675
Key Points

Question  Is cigarette smoking associated with an increased odds of having antineutrophil cytoplasmic antibody–associated vasculitis (AAV)?

Findings  In this case-control study of 473 patients with AAV compared with 1419 matched controls, cigarette smoking was associated with an increased odds of having AAV. This association was especially strong in patients with antimyeloperoxidase antibodies, who are increasingly recognized to have differences in genetic risk, pathogenesis, and response to treatment compared with those with proteinase 3 antibodies.

Meaning  The association between AAV and cigarette smoking identifies a modifiable risk factor for AAV and may suggest a possible pathogenic mechanism between respiratory exposures and development of AAV.

Abstract

Importance  Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic small vessel vasculitis characterized by circulating ANCAs targeting proteinase 3 (PR3) or myeloperoxidase (MPO) and associated with excess morbidity and mortality. Myeloperoxidase-ANCA–positive AAV and PR3-ANCA–positive AAV are increasingly recognized to have differences in genetic risk, pathogenesis, and response to treatment. Risk factors for AAV, including cigarette smoking, are poorly understood.

Objective  To examine the association between cigarette smoking and AAV.

Design, Setting, and Participants  This case-control study included a consecutive inception cohort of 484 patients with AAV diagnosed from 2002 to 2017 compared with a cohort of sex-, race-, and age-matched controls. Eleven cases were excluded owing to discordant smoking information in the electronic health record. Controls were randomly selected from participants recruited to the Partners HealthCare Biobank between its inception in 2010 and 2018 and who completed a smoking questionnaire and were not diagnosed with AAV (n = 30 536).

Exposures  Smoking status (current, former, never) and pack-years of cigarette smoking were determined from review of the electronic medical record and smoking questionnaires.

Main Outcomes and Measures  Patients with AAV were individually matched with 3 randomly-selected controls based on sex, race, and age (within 2 years difference). Conditional logistic regression was performed to examine the association between cigarette smoking and AAV using odds ratios (OR) and 95% confidence intervals (CIs).

Results  Overall, 473 cases were matched with 1419 controls (mean [SD] age, 59 [16] years; 281 women [59%], 396 white [84%]). Patients with AAV were more likely to be former (OR, 1.6; 95% CI, 1.3-2.0) or current smokers (OR, 2.7; 95% CI, 1.8-4.1); there was a dose-response relationship according to pack-years of exposure (P < .001). These associations were especially 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 participants with PR3-ANCA–positive AAV (former smokers: OR, 1.3; 95% CI, 0.9-2.0; current smokers: OR, 1.7; 95% CI, 0.8-3.5). After stratifying by selected demographics and disease manifestations, these associations remained strong.

Conclusions and Relevance  Cigarette smoking was associated with AAV, especially MPO-ANCA–positive AAV. Further studies are needed to investigate a potential pathogenic mechanism.

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