Background/Purpose: It is well recognized that smoking has immuno-modulatory effects in several chronic inflammatory disorders. For ANCA-associated vasculitis (AAV), which includes granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the influence of smoking on disease risk and expression is not well understood.  A small retrospective study suggested a protective effect of smoking on ENT manifestations. We investigated the relationship between smoking and AAV characteristics within two large, prospectively collected cohorts. 

Methods: The analyses used data from newly-diagnosed patients with AAV who were enrolled in 4 international randomized controlled trials of the Europe Vasculitis Society (EUVAS).  Disease characteristics at diagnosis (age, sex, diagnosis, ANCA subtype, system involvement, BVAS, creatinine, CRP) were compared according to smoking status (current versus non-current; ever versus never). The analyses were repeated for the cumulative disease characteristics of consecutive patients with AAV from the Vasculitis Quality of Life (VASQoL) study, a multi-center cross-sectional study involving rheumatology and renal clinics across the United Kingdom. Univariate analyses used Chi² and Mann-Whitney tests for categorical and continuous variables, respectively; logistic regression was used for age-adjusted analyses.

Results: Of the 535 EUVAS patients, smoking data was available for 342 (GPA/MPA ratio: 186/156; males: 57%; median age: 60 years) among which 36 (11%) were current smokers and 158 (46%) ever smokers. Of the 360 VASQoL patients (GPA/MPA ratio: 265/95; males: 49%; median age: 64 years), all with complete smoking data, 26 (7%) were current smokers and 191 (53%) were ever smokers. Compared with non-current smokers, current smokers were significantly more likely to have vasculitis-related gastrointestinal (GI) manifestations in the EUVAS and in the VASQoL cohorts (17% vs. 6% [p=0.026] and 12% vs. 4% [p=0.044], respectively). In addition, VASQoL current smokers were significantly more likely to experience cutaneous (48% vs. 28%, p=0.035) and less likely to experience ENT (44% vs. 64%, p=0.046) manifestations. No other differences in AAV characteristics, including anti PR3/MPO status, were observed in the EUVAS and VASQoL cohorts although current smokers were younger than non-current smokers (p=0.047 and p=0.021, respectively).  Age-adjustment did not alter the interpretation of the identified associations of current smoking with disease characteristics. Both EUVAS and VASQoL ever-smokers were more likely to be males (both p<0.0001) and older (both p=0.02) but ever-smoking was not associated with clinical AAV characteristics in either cohort.  

Conclusion: These analyses of 2 independent AAV cohorts indicate that current smoking is positively associated with GI involvement, a finding which is in keeping with the established association between smoking and risk for Crohn’s disease. The VASQoL data also replicated a previous report supporting that smokers less often present with ENT manifestations.  The lack of phenotype-modifying effects of ever-smoking could suggest an acute immune-modulatory effect of smoking in AAV.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-smoking-on-the-clinical-expression-of-anca-associated-vasculitis/