COPD May Be Causally Linked to Rheumatoid Arthritis, Osteoarthritis

Along with a common occurrence between the two in a single patient, new data observes a potentially causal relationship between chronic obstructive pulmonary disease (COPD) and autoimmune diseases including rheumatoid arthritis (RA) and osteoarthritis.

Mendelian randomization (MR) research from a team of investigators at the First Affiliated Hospital of Xi’an Jiaotong University in China showed that patients with RA and osteoarthritis were significantly associated with increased risk of developing COPD based on genetic susceptibility. The findings align with increasing evidence that the pathogenesis of autoimmune disease may play a critical role in the development of COPD.

“Serum from COPD patients has been shown to produce autoantibodies that react with antigens known to be associated with autoimmune diseases, including RA,” the team wrote. “Further research is needed to investigate the potential mechanisms by which RA contributes to COPD.

Interestingly, prior research has suggested an association in the opposite order—and to multiple chronic pulmonary diseases. A 2020 analysis reported a 53% increased risk of developing RA among women with asthma than in those without asthma nor COPD (hazard ratio [HR], 1.53; 95% CI, 1.24 – 1.88). Among women with COPD, the associated risk of RA was nearly 3-fold (HR, 2.85; 95% CI, 1.63 – 4.99).

Investigators led by Zhihong Shi sought to analyze the potential causal relationship between COPD and 4 common autoimmune diseases: RA; osteoarthritis; systemic lupus erythematosus (SLE); and inflammatory bowel disease (IBD). They conducted the MR study due to reliable inference of causal relationships between risk factors and disease outcomes. Additionally, no other research of this type has observed the COPD – autoimmune disease relationship in such a way before.

“Although both COPD and autoimmune diseases are common, their co-occurrence has not received sufficient attention,” they noted. “Often, patients with autoimmune diseases who take immunosuppressive drugs to control their condition are more susceptible to infection, which can lead to acute exacerbations of COPD, ultimately imposing a heavy economic and social burden.”

Shi and colleagues conducted an analysis of summary data on COPD and autoimmune disease via publicly available genome-wide association studies summary data. They initially used an inverse-variance weighted method to observe a causal impact of COPD on autoimmune diseases in the sample, then a reverse MR analysis for the 4 autoimmune diseases on COPD.

In assessing the causal effect of COPD on autoimmune diseases, investigators included 13 single nucleotide polymorphisms (SNPs) strongly related to COPD. None of the 4 autoimmune diseases were significantly associated to a causal risk due to COPD, based on the inverse-variance weighted and standard MR analysis.

In the reverse MR analysis using ≤27 SNPs to assess the causal impact of autoimmune diseases on COPD, however, investigators observed a significant risk between RA (odds ratio [OR], 377.313; 95% CI, 6.625 – 21489.932; P = .004) and osteoarthritis (OR, 11.097; 95% CI, 1.583 – 77.796; P = .015) and risk of developing COPD. A follow-up sensitivity analysis reinforced the associations.

The investigators noted that their findings correlate with observational studies that have linked RA to interstitial lung disease (ILD) as well as COPD, regardless of key risk factors including smoking.

“Currently, there is no concrete evidence to explain the specific interplay between the development of both diseases when they coexist,” they noted. “Some studies suggest that the use of immunosuppressants is not significantly associated with the prognosis of COPD. However, other research suggests a correlation with the production of autoantigens and decreased immune tolerance in COPD patients, with a significant increase in serum autoantibody titers related to disease severity.”

Regardless, they concluded that their MR analysis points toward a potential causal relationship between RA, osteoarthritis and COPD. They recommended, amid efforts to further understand the interplay of autoimmune and respiratory disease, that clinicians consider screening for COPD in patients with RA or osteoarthritis.

References

1. ^{Yu X, Cheng X, Lv L, et al. The association between chronic obstructive pulmonary disease and autoimmune diseases: a bidirectional Mendelian randomization study. Front Med (Lausanne). 2024;11:1331111. Published 2024 Mar 5. doi:10.3389/fmed.2024.1331111}
2. ^{Rosenfeld S. Asthma, COPD Increase Rheumatoid Arthritis Risk. HCPLive. Published March 5, 2020. https://www.hcplive.com/view/asthma-copd-increase-rheumatoid-arthritis-risk}