Smoking Not Associated With Systemic Sclerosis-Specific Cutaneous, Pulmonary Manifestations

Smoking status in patients with systemic sclerosis (SSc) was not significantly associated with SSc-specific cutaneous or pulmonary changes, despite findings indicating bronchial and alveolar manifestations in smokers with SSc, according to research published in Arthritis & Rheumatology.

While smoking is known to increase vasoconstriction and free radical exposure, there have been conflicting results regarding the effect of smoking on SSc progression and severity. Investigators sought to parse the effects of smoking tobacco on the evolution of pulmonary and skin complications in patients with scleroderma in the largest prospective study of its kind.

Data was drawn from the multinational longitudinal European Scleroderma Trials and Research (EUSTAR) database. Baseline and 12- to 24-month follow-up information was recorded, using self-reported smoking history and the comprehensive smoking index (CSI) to categorize participant smoking status. Multivariable regression analyses were used to assess any associations between smoking and organ involvement severity and progression via examination of multiple disease parameters, including forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) and modified Rodnan skin score (mRSS). Risks were reported using odds ratios (OR).

A total of 3319 patients (mean age, 57 years; 85% women) from the EUSTAR database were enrolled between 2013 and 2017. Data show that 66% never smoked, while 23% reported prior smoking and 11% were current smokers. Follow-up visits occurred on average at 1.4 years after baseline. Current smokers reported an average of 27 pack-years.

Compared with prior smokers or patients who never smoked, current smokers displayed a lower percentage of anti-topoisomerase antibodies (40% and 45% vs 31%, respectively). At baseline, patients who had never smoked had a higher FEV1/FVC ratio compared with current or prior smokers (P <.001), and this ratio decreased more rapidly in current smokers vs prior smokers (P =.01) or never smokers (P =.05).

At baseline, the mRSS score was similar in all groups. The scores decreased over time and remained comparable in groups without significant differences. There was no clear association between smoking and the development of digital ulcers, although current smokers with >25 pack-years of smoking had an increased risk of having digital ulcers compared with patients who never smoked (OR, 1.6; P = .02). Researchers also observed that a higher CSI correlated with ulcer prevalence at baseline (OR, 1.2; P =.002).

Study limitations included lack of verification of patient smoking information and possible selection bias towards healthier patients.

Although the EUSTAR study showed a higher prevalence of digital ulcers in heavy smokers and showed an adverse effect of smoking on pulmonary airways, it did not demonstrate any significant effects of smoking on SSc-specific cutaneous or pulmonary parameters. The researchers noted that “these data argue against a major role of tobacco associated free radicals, vasoconstrictory and immunomodulatory effects in the pathogenesis of SSc vasculopathy and fibrosis.”

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Reference

Jaeger VK, Valentini G, Hachulla E, et al. Smoking in systemic sclerosis: a longitudinal European Scleroderma Trials and Research group study [published May 21, 2018]. Arthritis Rheumatol. doi:10.1002/art.40557