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ORIGINAL RESEARCH article

Front. Psychiatry
Sec. Addictive Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1429297
This article is part of the Research Topic Molecular Mechanisms in Psychiatry 2023: Addictive Disorders View all 6 articles

Nicotine dependence is associated with an increased risk to develop chronic, non-communicable inflammatory disease: A largescale retrospective cohort study

Provisionally accepted
Khalaf Kridin Khalaf Kridin 1Cristian Papara Cristian Papara 1David A De Luca David A De Luca 1Jan Philipp Klein Jan Philipp Klein 1Katja Bieber Katja Bieber 1Marlene A Ludwig Marlene A Ludwig 1Artem Vorobyev Artem Vorobyev 1Astrid Dempfle Astrid Dempfle 2Ralf J Ludwig Ralf J Ludwig 1*
  • 1 Department of Dermatology, University of Lübeck, Lübeck, Germany
  • 2 University of Kiel, Kiel, Schleswig-Holstein, Germany

The final, formatted version of the article will be published soon.

    Chronic, non-communicable inflammatory diseases (CIDs) affect large parts of the population, imposing a significant morbidity, encompassing a substantial comorbidity. Thus, they are a major medical burden with a high unmet need. CIDs develop over the span of several years and the risk to develop CIDs has been linked to genetic and environmental factors. Thus, modification of environmental factors is a promising approach for 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, 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. 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 to develop any or any of 38 CIDs in 881,192 EHRs from individuals with nicotine dependence to PSM-matched unexposed counterparts. 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 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. Our study emphasizes the importance of preventive measures targeting nicotine addiction to reduce the global burden of CIDs.

    Keywords: Nicotine dependence, Chronic inflammatory diseases, Asthma, lupus, COPD, Dermatomyositis, granulomatosis with polyangiitis (GPA), Pyoderma Gangrenosum

    Received: 12 May 2024; Accepted: 08 Jan 2025.

    Copyright: © 2025 Kridin, Papara, De Luca, Klein, Bieber, Ludwig, Vorobyev, Dempfle and Ludwig. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ralf J Ludwig, Department of Dermatology, University of Lübeck, Lübeck, 23562, Germany

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