Cigarette smoking patterns preceding primary Sjögren's syndrome

Abstract

Background: Cigarette smoking is a well-established risk factor for several autoimmune diseases, but its role in primary Sjögren's syndrome (pSS) remains unclear. Here, we investigated the association between cigarette smoking and subsequent development of pSS.

Methods: Information on smoking habits was collected from lifestyle habit questionnaires of patients with pSS (n=815) and a matched control group (n=4425) for a case-control study. Differences in smoking exposure were analysed by conditional logistic regression. Potential interactions between smoking and risk-associated human leucocyte antigens (HLA) were assessed by multivariate regression.

Results: The fraction of patients with pSS having ever smoked prior to diagnosis was lower than in controls (OR 0.67, 95% CI 0.55 to 0.81). Current smoking at diagnosis was also less prevalent in cases (OR 0.37, 95% CI 0.26 to 0.53). However, period prevalence of smoking during early adulthood was not statistically different from controls (OR 0.89, 95% CI 0.66 to 1.22) but markedly decreased over time. This was partly due to patients being more prone to stop smoking, starting already 30 years prior to diagnosis (OR 2.01, 95% CI 1.22 to 3.30). Smoking patterns were also stratified by autoantibody status, yielding similar estimates. No interaction effects between HLA-DRB1 haplotypes and smoking were observed.

Conclusion: The observed smoking patterns indicate that individuals who develop pSS smoke equally much as the general population during early life but are then more prone to stop. The data can be interpreted as smoking conferring protective effects, or reflecting early symptoms of pSS that affect smoking habits, emphasising the slow, progressive development of the disease.

Keywords: Autoantibodies; Sjogren’s Syndrome; Smoking.

Figure 1

Period prevalence of smoking in relation to pSS diagnosis, stratified by SSA and SSB status. Error bars mark 95% CIs. pSS, primary Sjögren’s syndrome; SSA, Ro/SSA autoantibodies; SSB, La/SSB autoantibodies.

Figure 2

Cumulative pack-years of regular smoking prior to pSS diagnosis date, stratified by SSA and SSB status. Error bars demark 95% CIs. pSS, primary Sjögren’s syndrome; SSA, Ro/SSA autoantibodies; SSB, La/SSB autoantibodies.

Figure 3

Cumulative pack-years of regular smoking prior to pSS diagnosis date, stratified by HLA haplotype. Error barks demark 95% CIs. HLA, human leucocyte antigen; pSS, primary Sjögren’s syndrome. *n=155 cases, n=515 controls; †n=133 cases, n=554 controls; ‡n=119 cases, n=782 controls.

Figure 4

ORs of ever regular smoking and interaction effects with HLA-DRB1 alleles in patients with pSS with Ro/SSA and/or La/SSB autoantibodies compared to controls. The reference group consists of never-smokers and non-carriers of the investigated HLAs; HLA, human leucocyte antigen; pSS, primary Sjögren’s syndrome.