Nicotine dependence is associated with an increased risk of developing chronic, non-communicable inflammatory disease: a large-scale retrospective cohort study

Khalaf Kridin; Cristian Papara; Katja Bieber; David A De Luca; Jan Philipp Klein; Marlene A Ludwig; Philip Curman; Artem Vorobyev; Astrid Dempfle; Ralf J Ludwig

doi:10.3389/fpsyt.2025.1429297

Nicotine dependence is associated with an increased risk of developing chronic, non-communicable inflammatory disease: a large-scale retrospective cohort study

Front Psychiatry. 2025 Feb 12:16:1429297. doi: 10.3389/fpsyt.2025.1429297. eCollection 2025.

Authors

Khalaf Kridin^#^{1

2

3}, Cristian Papara^#⁴, Katja Bieber^#¹, David A De Luca⁴, Jan Philipp Klein⁵, Marlene A Ludwig⁶, Philip Curman^{1

7

8

9}, Artem Vorobyev¹⁰, Astrid Dempfle^#¹¹, Ralf J Ludwig^#¹⁰

Affiliations

¹ Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
² Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
³ Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel.
⁴ Institure and Comprehensive Centre for Inflammation Medicine, University Hospital Schleswig-Holstein (UKSH), Lübeck, Germany.
⁵ Department of Psychiatry, Psychosomatics and Psychotherapy, Lübeck University, Lübeck, Germany.
⁶ Independent Researcher, Groß Grönau, Germany.
⁷ Dermato-Venereology Clinic, Karolinska University Hospital, Stockholm, Sweden.
⁸ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁹ Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Lübeck, Germany.
¹¹ Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany.

^# Contributed equally.

Abstract

Introduction: Chronic, non-communicable inflammatory diseases (CIDs) affect a large portion of the population, imposing a significant morbidity, encompassing a substantial mortality. Thus, they are a major medical burden with a high unmet need. CIDs develop over the span of several years, and the risk of developing CIDs has been linked to genetic and environmental factors. Thus, modification of environmental factors is a promising approach for the prevention of CIDs. Among modifiable environmental factors that have been linked to the CID risk is nicotine dependence. However, for only few CIDs, compelling evidence suggests that nicotine dependence increases (e.g., rheumatoid arthritis and asthma) or decreases (e.g., pemphigus) the CID risk. For most CIDs, there are inconsistent, scant, or no reports on the risk of CID associated with nicotine dependence.

Methods: To address this gap, we leveraged TriNetX, analyzing data from over 120 million electronic health records (EHRs). Using propensity score matching (PSM) to control for age, sex, ethnicity, and other CID risk factors, we contrasted the risk of developing any or any of the 38 CIDs in 881,192 EHRs from individuals with nicotine dependence to PSM-matched unexposed counterparts.

Results: The analytical pipeline was validated by demonstrating an increased risk of individuals exposed to nicotine dependence for subsequent diagnosis of myocardial infarction, malignant neoplasm of the lung, and chronic obstructive pulmonary disease. Overall, 16.8% of individuals with nicotine dependence developed CIDs, compared to 9.6% of individuals not exposed to nicotine dependence (hazard ratio 2.12, confidence interval 2.10-2.14, p < 0.0001). Investigating single CIDs, nicotine dependence imposed increased risks for 23 of the 38 investigated diseases, i.e., dermatomyositis, granulomatosis with polyangiitis, pyoderma gangrenosum, and immune thrombocytopenic purpura. The sex-stratified analysis revealed few sex-specific differences in CID risk.

Discussion: Our study emphasizes the importance of preventive measures targeting nicotine addiction to reduce the global burden of CIDs.

Keywords: COPD; asthma; chronic inflammatory diseases; dermatomyositis; granulomatosis with polyangiitis (GPA); lupus; nicotine dependence; pyoderma gangrenosum.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC 2167), the Research Training Group “Autoimmune Pre-Disease” (GRK 2633), the Collaborative Research Center “PANTAU” (SFB 1526), and DFG Individual Grant LU 877/25-1, all from the Deutsche Forschungsgemeinschaft and the Schleswig-Holstein Excellence-Chair Program from the State of Schleswig Holstein.