Causal association of rheumatoid arthritis with obstructive lung disease: Evidence from Mendelian randomization study.

Ziqin Cao, Qiangxiang Li, Jianhuang Wu, Yajia Li

Journal: Heart & lung : the journal of critical care 2023;62():35-42

PMID: 37302263

Free Full Text on Elsevier Science View on PubMed

Plain Language Summary

There has been shown to be an association between rheumatoid arthritis (RA) and obstructive lung disease (ORDs), however it is unclear if RA causes ORDs. This study aimed to determine the links between the two diseases on a genetic level. The results showed that if individuals were genetically predisposed to the development of RA, then there was an increased risk for the development of several ORDs including chronic obstructive pulmonary disorder (COPD), asthma, and asthma associated pneumonia. It was concluded that individuals with a genetic predisposition for RA may be at a higher risk for the development of ORDs such as asthma, COPD, and pneumonia. This study could be used by healthcare professionals to understand that inflammation associated with RA may trigger other inflammatory diseases.

Abstract

BACKGROUND

Observational studies have found an association between rheumatoid arthritis (RA) and risk of obstructive lung disease (ORDs). However, whether RA plays a role in ORDs development remains unclear.

OBJECTIVES

This study aimed to explore the causal association of RA with ORDs.

METHODS

Both univariable and multivariable Mendelian randomization (MR) analyses were employed. Summary statistics for RA were obtained from the genome-wide association study (GWAS) meta-analysis, and the GWAS data source of ORDs, including the chronic obstructive pulmonary disease (COPD) and asthma, was accessed from the FinnGen Biobank. Causal Analysis Using Summary Effect Estimates (CAUSE) method was used to improve statistical power. multivariable and two-step mediation MR was applied to calculate the independent and mediated effects.

RESULTS

The causal estimates by univariable and CAUSE results indicated genetic predisposition to RA had an effect on the increased risk of asthma/COPD (A/C) (OR = 1.03; 95% CI: 1.02-1.04), COPD/asthma related infections (ACI) (OR = 1.02; 95% CI: 1.01-1.03) and COPD/asthma related pneumonia or pneumonia derived septicemia (ACP) (OR = 1.02; 95% CI: 1.01-1.03). Genetic predisposition to RA was significantly associated with early onset COPD (OR = 1.02; 95% CI: 1.01-1.03) and asthma (OR = 1.02; 95% CI: 1.01-1.03) risk and suggestively associated with non-allergic asthma (nAA) risk. After adjustment for confounders, independent causal effects remained for the associations of RA with risk of A/C, ACI, and ACP, as well as COPD, early-onset COPD, and asthma [total, nAA and allergic asthma (AA)] risk. Mediation analyses revealed no potential mediator.

CONCLUSION

This study indicates a causal effect of increased genetic predisposition to RA on an increased risk of ORDs, including COPD and asthma, especially early-onset COPD and nAA, and on asthma/COPD related infections, pneumonia or pneumonia derived septicemia.

Address: Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.; Ningxia Geriatric Disease Clinical Research Center, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750001, China; National Clinical Research Center for Geriatric Disorders of Xiangya Hospital, Central South University (Sub-center of Ningxia), Yinchuan, Ningxia Hui Autonomous Region 750001, China; Hunan People's Hospital, Geriatrics Institute of Hunan Province, Changsha, China, Changsha 410002, China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China; Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. Electronic address: [email protected].

DOI: 10.1016/j.hrtlng.2023.05.020