Obstructive lung diseases and risk of rheumatoid arthritis

ABSTRACT

Introduction: Smoking is an established risk factor for both lung diseases and rheumatoid arthritis (RA). Chronic mucosal airway inflammation may result in immune tolerance loss, neoantigen formation, and production of RA-related autoantibodies that increase the subsequent risk of RA. In this review, we aimed to summarize the current evidence supporting the role of obstructive lung diseases and subsequent risk of RA.

Areas covered: We identified scientific articles discussing the biologic mechanisms linking mucosal airway inflammation and RA risk. We also identified studies investigating asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, chronic tuberculous and nontuberculous mycobacterial infections, and interstitial lung disease with subsequent risk for RA.

Expert opinion: The current evidence supports the hypothesis that mucosal airway inflammation may increase the risk of developing RA. However, most studies investigating this relationship have been retrospective and may not have adequately addressed the role of smoking. Larger prospective studies may provide stronger evidence for obstructive lung disease and RA risk. Determining the role of obstructive lung disease in RA pathogenesis may provide opportunity for RA prevention and screening strategies, while identifying novel biologic mechanisms that could offer targets to improve treatment and outcomes.

KEYWORDS:

• ACPA
• asthma
• autoimmunity
• bronchiectasis
• COPD
• ILD
• inflammation
• obstructive lung disease
• rheumatoid arthritis

Article highlights

• Many potential biologic mechanisms may place patients with obstructive lung diseases at increased risk for rheumatoid arthritis (RA).

• Chronic airway inflammation may lead to neoantigen production, immune tolerance breakdown, and RA-related autoantibody production prior to the systemic and articular involvement of RA.

• Asthma is the most studied obstructive lung disease for risk of RA and there are conflicting results; most studies suggest that asthma may increase RA risk, but one study found a possible protective effect of asthma on RA risk. Many of these studies had limited ability to account for the possible effect of smoking in explaining this relationship and most were retrospective.

• Fewer studies have investigated chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, chronic tuberculous and nontuberculous mycobacterial infections, and interstitial lung disease for subsequent risk of RA, but these are hypothesized to play a role in RA pathogenesis.

Declaration of interest

JA Sparks has received research support from Amgen and Bristol-Myers Squibb and performed consultancy for Optum, Janssen, and Gilead unrelated to this work. M Cho has received grant funding from GSK, consulting fees from Genentech, and speaking fees from Illumina unrelated to this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

JA Sparks is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253, and P30 AR072577), the Rheumatology Research Foundation K Supplement Award, and the Brigham Research Institute. The funders had no role in the decision to publish or preparation of this 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.