Date Published: February 6, 2017
Publisher: Public Library of Science
Author(s): Donald U. Stone, Dustin Fife, Michael Brown, Keith E. Earley, Lida Radfar, C. Erick Kaufman, David M. Lewis, Nelson L. Rhodus, Barbara M. Segal, Daniel J. Wallace, Michael H. Weisman, Swamy Venuturupalli, Michael T. Brennan, Christopher J. Lessard, Courtney G. Montgomery, R. Hal Scofield, Kathy L. Sivils, Astrid Rasmussen, Masataka Kuwana.
To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren’s syndrome (SS) and non-Sjögren’s sicca (non-SS sicca).
Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers.
Current smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22–0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15–0.44, FDR q = 1.52x10E-06), focus score ≥1 (OR 0.22, 95%CI 0.13–0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2–0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39–0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption.
Current tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration.
Tobacco use creates a tremendous burden on the health care system and is the largest non-communicable source of disease globally; annual tobacco-attributable deaths surpassed 5 million in 2010.[1, 2] Cigarette smoking has wide-ranging effects on the user depending on both extrinsic and intrinsic factors, with a well-described influence on oncogenesis, pulmonary function, vascular health, and immune response. [3–10] The mechanisms of disease may be as diverse as the contents of cigarette smoke; carbon monoxide, cyanide, nicotine, benzene, formaldehyde, methanol, ammonia, tar and nearly 4000 other chemicals identified in cigarette smoke.
The cohort consisted of 1288 subjects: 596 participants entered the study with a clinical diagnosis of SS that was supported by pSS AECG classification at the SRC in 378 cases (63.4%); 651 had no prior clinical SS diagnosis but 190 (29.1%) met AECG criteria for pSS, while 41 (of which 19 [46%] were classified as pSS) were uncertain about the diagnostic impression of their referring physician. Thus, based on our comprehensive research evaluation at the SRC, 587 participants were classified as primary SS and 701 as non-SS sicca. The sociodemographic features of the participants are shown in Table 1. While SS and non-SS sicca participants had similar gender and ethnicity distributions, the latter were younger and less likely to be Asian (p = 9.39x10E-06 and p = 0.007, respectively), and more likely to be Native American (p = 0.03) than subjects classified as SS.
We explored the smoking behavior of a large cohort of patients with sicca syndrome and identified a strong protective effect of tobacco smoking against disease classification as primary SS and objective measures of autoimmunity. This effect persisted after correction for multiple testing and was consistently observed when comparing current to past smoking, and ever to never smoking. Exposure to tobacco smoke has been associated with a large number of deleterious effects on health. It is a well-known modulator of inflammatory and immune mechanisms and its use has been associated with an increase in disease risk, severity and flares of rheumatic diseases, in particular rheumatoid arthritis.[7, 8, 12–15] However, the precedent set by ulcerative colitis, Behçet’s disease, and aphthous stomatitis[16, 20] raises the possibility of a protective effect of smoking upon the development of some immune-mediated disorders. Few other studies have focused on the role of tobacco in Sjögren’s syndrome, which is a natural model to explore given that smoking has also been positively associated with oral and salivary gland diseases and symptoms of dry eyes.[40, 41]