Smoking Behaviour and the Progression of Organ Manifestations in Systemic Sclerosis: A Longitudinal European Scleroderma Trials and Research Group Study

Veronika K. Jaeger¹, Gabriele Valentini², Eric Hachulla³, Franco Cozzi⁴, Oliver Distler⁵, Paolo Airò⁶, Lazlo Czirjak⁷, Yannick Allanore⁸, Elise Siegert⁹, Edoardo Rosato¹⁰, Marco Matucci-Cerinic¹¹, Lisa Maria Bambara¹², Joerg C. Henes¹³, Patricia Carreira¹⁴, Vanessa Smith¹⁵, Francesco Del Galdo¹⁶, Christopher Denton¹⁷, Susanne Ullman¹⁸, Ellen de Langhe¹⁹, Valeria Riccieri²⁰, Juan José Alegre²¹, Simona Rednic²², Ulf Müller-Ladner²³ and Ulrich A. Walker¹, ¹Department of Rheumatology, University Hospital Basel, Basel, Switzerland, ²Second University of Naples, Naples, Italy, ³Department of Internal Medicine, Université de Lille, Lille, France, ⁴Division of Rheumatology, Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy, ⁵Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland, ⁶Rheumatology and Clinical immunology Unit, Spedali Civili of Brescia, Brescia, Italy, ⁷Department of Rheumatology and Immunology, University of Pécs, Pécs, Hungary, ⁸Department of Rheumatology, University Paris Descartes and Cochin Hospital, Paris, France, ⁹Rheumatology and Clinical Immunology, University Hospital Charité, Berlin, Germany, ¹⁰Sapienza University of Rome, Rome, Italy, ¹¹Dept of Medicine/Div of Rheum, University of Florence, Florence, Italy, ¹²University of Verona, Verona, Italy, ¹³Department of Internal Medicine II, Division of Rheumatology, University Hospital Tuebingen, Tuebingen, Germany, ¹⁴Department of Rheumatology, Hospital Universitario 12 de Octubre, Madrid, Spain, ¹⁵Faculty of Internal Medicine, Ghent University, Ghent, Belgium, ¹⁶Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, ¹⁷Department of Rheumatology, University College London, Royal Free Hospital, London, United Kingdom, ¹⁸Department of Dermatology, Copenhagen University Hospital, Copenhagen, Denmark, ¹⁹Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium, ²⁰Divisione di Reumatologia, Università di Roma La Sapienza, Roma, Italy, ²¹Sección de Reumatología Hospital Universitario Dr Peset Valencia, Valencia, Spain, ²²Clinica Reumatologie, University of Medicine & Pharmacy, Cluj-Napoca, Romania, ²³Justus-Liebig-University Giessen, Department of Internal Medicine and Rheumatology, Kerckhoff-Klinik, Bad Nauheim, Germany, Bad-Nauheim, Germany

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Systemic sclerosis and tobacco use

Session Information

Date: Monday, November 6, 2017

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Clinical Aspects and Therapeutics Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Systemic sclerosis (SSc) is a rare, multisystem autoimmune disorder. It is characterized by generalized microangiopathy, in the pathogenesis of which hypoxia and oxidative stress have been implicated. Tobacco inhalation increases free radicals and strongly promotes vascular damage. So far, data available with regards to a role of tobacco exposure with SSc severity and progression are scarce.

We aimed to assess the associations of smoking with the speed of worsening of organ manifestations, namely lung involvement (forced vital capacity, FVC; forced expiratory volume, FEV1/FVC ratio; diffusing capacity for carbon monoxide corrected for alveolar volume, DLCO/VA), skin involvement (modified Rodnan skin score; mRSS), and digital ulcers (DU) in the European scleroderma trials and research (EUSTAR) database.

Methods:

Adult SSc patients from the EUSTAR cohort with a follow-up visit 12-24 months after the baseline visit and available data on their smoking habits were included.

The associations of smoking behavior (never smokers vs ex-smokers vs current smokers) with the change in disease manifestations between baseline and follow up were assessed using multivariable linear or logistic regression analyses adjusting for age, sex, autoantibody status, disease duration, SSc subset. Missing data were imputed using multiple imputations.

Results:

Of the 3,319 patients included (mean age 57 years, standard deviation [SD] 14; 85% female; 29% diffuse SSc), 66% of patients stated that they never smoked, 23% were ex-smokers and 11% were current smokers. The average ex-smokers had smoked 18 pack-years (SD 21) during a time of 19 years (SD 12) and quit smoking 15 years (SD 13) ago. The average current smoker smoked 27 pack-years (SD 30) during a time of 30 years (SD 13).

On average, the FEV1/FVC ratio changed from 96.5 (SD 14) at baseline to 96.0 (SD 13) at follow up. In current smokers, the ratio decreased significantly faster during the observation period than in never smokers after adjustment (β=-4%, p<0.001). This was not observed in ex-smokers (p=0.7).

The DLCO/VA decreased on average from 78.4 (SD 17) to 76.8 (SD 17). The decrease of DLCO/VA during the observation period was not associated with smoking behavior.

The mRSS changed between baseline and follow-up from an average of 7.7 (SD 8) to 7.3 (SD 7); the change in mRSS was not strongly and clinically meaningfully associated with smoking behavior.

Smoking behavior was not associated with the presence of DU at baseline. The occurrence of new DU during the observation period in patients without any DU prior to or at baseline was negatively associated with current smoking (OR 0.5, p=0.03) but not with previous smoking (OR 1.1, p=0.7).

Conclusion:

The adverse effect of smoking on bronchial airways that is known in the general population is replicated in the SSc population. The lack of a measurable adverse effect of smoking on the speed of worsening of cutaneous and pulmonary SSc manifestations argues against a major role of tobacco associated free radicals and vasoconstriction in the pathogenesis of SSc vasculopathy and fibrosis. Similarly, our data do not support an adverse effect of smoking on the presence or absence of DU.

Disclosure: V. K. Jaeger, None; G. Valentini, None; E. Hachulla, None; F. Cozzi, None; O. Distler, Actelion, 5,Bayer, 5,Biogen Idec, 5,Boehringer Ingelheim, 5,ChemomAb, 5,espeRare Foundation, 5,Genentech/Roche, 5,GlaxoSmithKline, 5,Inventiva, 5,Lilly, 5,Medac, 5,MedImmune, 5,Mitsubishi Tanabe Pharma, 5,Pharmacyclics, 5,Novartis Pharmaceutical Corporation, 5,Pfizer Inc, 5,Sanofi, 5,Sinoxa, 5,UCB in the area of potential treatments of scleroderma and its complications, 5,Patent mir-29 for the treatment of systemic sclerosis licensed, 5,Actelion, 2,Bayer, 2,Biogen Idec, 2,Boehringer Ingelheim, 2,ChemomAb, 2,espeRare Foundation, 2,Genentech/Roche, 2,GlaxoSmithKline, 2,Inventiva, 2,Lilly, 2,Medac, 2,Medimmune, 2,Mitsubishi Tanabe Pharma, 2,Pharmacyclics, 2,Novartis, 2,Pfizer Inc, 2,Sanofi, 2,Sinoxa, 2,UCB in the area of potential treatments of scleroderma and its complications, 2,Patent mir-29 for the treatment of systemic sclerosis licensed, 2; P. Airò, None; L. Czirjak, None; Y. Allanore, None; E. Siegert, None; E. Rosato, None; M. Matucci-Cerinic, None; L. M. Bambara, None; J. C. Henes, None; P. Carreira, None; V. Smith, None; F. Del Galdo, None; C. Denton, None; S. Ullman, None; E. de Langhe, None; V. Riccieri, None; J. J. Alegre, None; S. Rednic, None; U. Müller-Ladner, None; U. A. Walker, None.

To cite this abstract in AMA style:

Jaeger VK, Valentini G, Hachulla E, Cozzi F, Distler O, Airò P, Czirjak L, Allanore Y, Siegert E, Rosato E, Matucci-Cerinic M, Bambara LM, Henes JC, Carreira P, Smith V, Del Galdo F, Denton C, Ullman S, de Langhe E, Riccieri V, Alegre JJ, Rednic S, Müller-Ladner U, Walker UA. Smoking Behaviour and the Progression of Organ Manifestations in Systemic Sclerosis: A Longitudinal European Scleroderma Trials and Research Group Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/smoking-behaviour-and-the-progression-of-organ-manifestations-in-systemic-sclerosis-a-longitudinal-european-scleroderma-trials-and-research-group-study/. Accessed .

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