The Roles of Cigarette Smoking and the Lung in the Transitions Between Phases of Preclinical Rheumatoid Arthritis

  • Jeffrey A. Sparks
  • Elizabeth W. Karlson
Rheumatoid Arthritis (LW Moreland, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Rheumatoid Arthritis


While the etiology of rheumatoid arthritis (RA) remains to be fully elucidated, recent research has advanced the understanding of RA pathogenesis to the point where clinical trials for RA prevention are underway. The current paradigm for RA pathogenesis is that individuals progress through distinct preclinical phases prior to the onset of clinically apparent RA. These preclinical RA phases consist of genetic risk, local inflammation, presence of RA-related autoantibodies, asymptomatic systemic inflammation, and early non-specific symptoms prior to clinical seropositive RA. Epidemiologic studies have been important in forming hypotheses related to the biology occurring in preclinical RA. Specifically, studies associating cigarette smoking with overall RA risk as well as transitions between phases of preclinical RA were vital in helping to establish the lung as a potential important initiating site in the pathogenesis of seropositive RA. Herein, we review the epidemiology associating smoking with transitions in preclinical phases of RA as well as the recent literature supporting the lung as a critical site in RA pathogenesis.


Rheumatoid arthritis (RA) Lung Pulmonary Smoking Anti-citrullinated protein antibodies (ACPA) Pre-RA 


Compliance with Ethical Standards

Conflict of Interest

Jeffrey A. Sparks and Elizabeth W. Karlson declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any primary data concerning studies with animals or human subjects.


Jeffrey A. Sparks was supported by the Rheumatology Research Foundation Scientist Development Award and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers K23 AR069688 and L30 AR066953. Elizabeth W. Karlson was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers R01 AR049880, K24 AR052403, and P60 AR047782. The funders had no role in the preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard University, its affiliated academic health care centers, or the National Institutes of Health.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Medicine, Division of Rheumatology, Immunology and AllergyBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

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